The Dangoor Centre for Personalized Medicine operates under the very able guidance and leadership of Prof. Shulamit Michaeli. Before assuming her present position as the Vice President for Research, Prof. Michaeli served as the Dean of the Mina and Everard Goodman Faculty of Life Sciences, and as the founding Director of the Nano-Medicine Centre at the Bar-Ilan Institute for Nanotechnology and Advanced Materials. In addition, for eight years she directed the Life Sciences and Medicine division of the Israel Science Foundation.
A microbiologist by training, Prof. Michaeli is an expert in researching medical issues and diseases. She has pioneered the use of nanotechnology in fighting diseases and creating nano-drugs for parasitic infections and cancer. Her extensive career, vast experience, deep devotion and caring personality all ensure that she will bring the Dangoor Centre to even greater heights and achievements.
Each of the researchers who comprise the core of our personalized medicine team have done post-doctorate work at leading research institutions abroad. Additional researchers working at affiliated hospitals expand the scope and impact of our in-house researchers. All of our scientists are leaders in their respective fields of research. As the Dangoor Centre for Personalized Medicine grows, additional researchers will be recruited to advance the Centre’s goals. The following is a current list of Dangoor Centre researchers:
Prof. Shulamit Michaeli
Professor Shulamit Michaeli is the Vice president for Research and the Director of the Dangoor Center for Personalized Medicine. As a microbiologist and a molecular parasitologits, her main research focuses on gene regulation at the level of RNA. In the last ten years she entered the field of nanotechnology and developed new Nano-drugs to fight cancer as well as Nano anti-parasitic drugs. She studies basic processing from RNA splicing, ribosome structure and function, the role of RNA modification, gene silencing and the structure and function of non-coding RNAs. She recently developed in collaboration with Professor Lellouche the first Nano-drug against Leishmania.
She was trained at Tel-Aviv University and was the first direct PhD student in the Faculty of Life Science. After receiving her PhD in bacteriology, she was a post-doctoral fellow at UC-Berkeley and UCSF for five years where she studied the sleeping sickness disease caused by parasites. Upon her return to Israel, she was a researcher at the Weizmann Institute in until joining the Bar-Ilan Faculty as a Professor. Prior to assuming her current role as VP, Prof. Michaeli served as the Dean of Faculty of Life Sciences and the founding Director of the Nano-Medicine Center for Nanotechnology (BINA). In addition, for eight years Professor Michaeli directed the Life Sciences and Medicine division of the Israel Science Foundation (ISF) and also was the head of the Israeli Association for Biochemistry and Molecular Biology. She participated in several EU consortia, and Israeli excellence research centers (I-core). Michaeli is a member of many national panels including the Psiphass project for sequencing of Israeli citizens. Professor Michaeli is also a member of the Technion Krotarion.
Prof. Michaeli was the first recipient in the Middle East of a ten year grant from the Howard Hughes Medical Institute and was an International scholar in molecular Parasitology of the HHMI. She has been awarded several prestigious prizes including: the Landau prize for excellence for her PhD work; the Israeli Microbiology Shilo and Ulizki prizes, the Clore prize at the Weizmann Institute, the Andre Lwoff prize given by the French Academy of Sciences, and the Landau prize In Microbiology.
Her wide knowledge base and vast experience in medical research in fields such as cancer and infectious diseases have led to the publication of over one hundred and twenty papers and several patents. She has supervised more than hundred M.Sc. and PhD students.
The Dangoor Center for Personalized Medicine
At the meeting of the Dangoor center held in February 2018 we identified the specific research strengths of our personalized medicine team. The researches in our interdisciplinary center come from the Faculties of Medicine, Life Sciences, Exact sciences, Engineering and Social Sciences. We aim to develop at least five focal points this coming year which will be augmented through the establishment of impact centers in Cancer and immunotherapy, RNA therapeutics, personalized genetics, Microbiota, Social aspects of personalized medicine. In years to come we hope to launch additional impact centers in in a bottom up approach.
I encourage all the members to regularly visit the Center's website as it is going serve as an informative and stimulating platform for sharing the progress and successes of the center, as well as keeping our members informed of various grant applications, awards etc.
Prof. Ran Tur-kaspa
Professor Ran Tur-Kaspa is the founding Dean of Bar-Ilan University’s School of Medicine in the Galilee.
A specialist in internal medicine and liver disease, Prof. Tur-Kaspa has many years of experience as a researcher, educator and practitioner. He has served as a researcher at the Albert Einstein Medical College of Medicine in NY, and at the National Institute of Health in Bethesda MD.
Before coming to Bar-Ilan, Prof. Tur-Kaspa was Vice Dean of the Sackler School of Medicine, Tel Aviv University.In addition to his duties as the Dean of the School of Medicine in the Galilee, Prof. Tur- Kaspa is the Head of the Rabin (Beilinson) Medical Center Liver Institute.
Prof. Tur-Kaspa has been actively involved in such organizations as:
- American Association for the Study of Liver Disease (recipient of the Association's Research Prize 1985)
- Israel Association for the Study of the Liver (Chairman, 1991 & 1994)
- Israel Society for Gastroenterology and Liver Diseases (Honorary Member since 2011)
- Israel Medical Association – Head of the Internal Medicine Board (non-surgical) in the Scientific Council (1999-2002)
Prof. Izhak Haviv
Cancer, Personalized Medicine, and Diagnostic Genomics
Prof. Izhak Haviv joined Bar-Ilan in 2012 from the Peter MacCallum Cancer Centre in Australia. There he became a leading exponent of personalized medicine and translational research. Today he is continuing that work at the School of Medicine in Safed developing ways to tailor each cancer patient’s chemotherapy treatment to his or her unique genetic make-up in order to optimally support his or her body in the fight against the disease.
In 2013, Haviv partnered in the treatment of thirty-two patients. This work was then represented in seven peer-reviewed papers published and four more in editorial review. With six outstanding PhD students working in his lab, his team can recruit about twenty patients each month.
In addition to his work with cancer, Haviv and his team are using other personalized medicine methods to understand and defeat “wasting syndrome” (cachexia), which may be responsible for a third of cancer-related deaths. They are also using genetic techniques to unravel certain mysteries of tongue cancer. This work may have wide ranging applications to other cancers.
Prof. Haviv is developing new individualized treatment methods to help cancer patients in Israel and around the world.
Annual Activity Report, March 2017
Kaposi’s sarcoma (KS) is a rare malignancy most commonly appearing in HIV carriers. In addition to HIV carriers, there are rare families with a genetic predisposition for KS. Some of these are of Jewish descent from Morocco. Professor Moshe Schaffer identified a few such families in his service as oncologist at the Poriya Medical Centre, Tiberias. In collaboration with the Dangoor Centre for Personalized Medicine, we performed whole exome sequencing of eight individuals from two such high-risk families, to identify the gene(s) and variant(s) responsible for this association. Our research revealed three candidate KS-causing alleles, and we are continuing to use genomic sequencing and clinical trials to confirm these correlations.
“There is something very Jewish about implementing high-throughput technologies into medical management. Jews have always resorted to creativity over brute force. In the 1970s, population-based screens to detect carriers of Tay-Sachs disease and sickle cell disease identified couples who had a 25% chance of passing either disorder to their offspring, enabling them to make informed reproductive decisions. But this achievement was obtained by an enormous amount of research hours in the lab. Today, using genomic technology and next-generation sequencing, we can shed light on the mechanisms of inheritance with remarkably light effort.” Izhak Haviv, describing the link between the Dangoor family and personalized medicine.
Prof. Tzipora C. Falik Zaccai
The Azrieli Faculty of Medicine
Our team, led by Prof. Tzipora Falik-Zaccai, searches for genes responsible for rare genetic disorders and investigates the function and biological pathway of the related protein. We combine our expertise in medical genetics and the working environment of the unique populations of the Galilee with the power of advanced genetic tools to identify genes and variants causing rare disorders. Our goal is to address and achieve a major impact on personalized medicine for individuals and communities belonging to a founder ancestor. Novel genes we discover and their related phenotype shed light on novel proteins and pathways which are crucial for healthy life. These patient-based discoveries broaden our understanding of proteins that become the target of personalized drug development for rare but also common disorders. Of particular interest are phenotypes of seizures, early onset dementia, N-glycanase deficiency, DNA repair disorders and cardiomyopathies. Our group efforts led to the recent identification of two novel genes, one involved in a novel cardio-cutaneous syndrome and another that causes a unique type of progressive leukoencephalopathy. Our work provides the option for personalized medicine to individuals from different ethnic groups in Israel. Patients benefit immediately from our group's research, which is used to develop new diagnostic tools for their families and communities, together with new biological and/or pharmaceutical insights.
Prof. Tzipora Falik-Zaccai received her MD cum laude from the Technion and is board certified in pediatrics (Israel) and medical genetics (Israel, USA). She is currently the director of the Institute of Human Genetics, Galilee Medical Center in Nahariya, and head of the Department of Genetics and the MD PhD program in the Azrieli School of Medicine, Bar Ilan University, Safed. The partnership of Prof. Falik-Zaccai’s institute with the laboratories at the Azrieli faculty of Medicine offers a unique translational medicine environment for addressing personalized medicine in a range of genetic disorders.
Dr. Orly Avni
Regulation of gene expression in the immune system in health and disease.
Dr. Orly Avni joined Bar-Ilan University in 2012 from the Technion Institute of Technology. Prior to the Technion, she was a postdoctoral fellow at Harvard Medical School where she became an expert in the regulation of gene expression, especially in the immune system.
While the healthy function of the immune system is critical for combating infectious diseases, it is also essential for maintaining normal homeostasis of organs such as heart and brain. Dysregulation of gene expression in the immune system is associated with many diseases, such as autoimmune disorders, allergies, chronic inflammation, neurodegenerative disorders, heart failure, and cancer.
Today at the Bar-Ilan University Faculty of Medicine in the Galilee, Dr. Avni and her team are developing ways to scrutinize abnormalities in immune system regulation at the genomic and epigenetic levels and use this information to tailor precision therapies. Two of the more significant studies Dr. Avni and her team are focusing on are:
(i) The effects of social stress on the increased risk for autoimmune disorders;
(ii) Genetically inherited fatal cardiomyopathy, which is the result of a failure to tune cardiac response to common inflammatory stressors. Their research aims to develop new strategies for novel tailored-treatment modalities.
Annual Activity Report, March 2017 - The effects of social stress on immune regulation are imprinted on gut microbiota, and the implication of this for autoimmunity
Dys-biotic gut microbiota and psychological/social stress were both found to be associated with increased occurrence of autoimmune disorders, and we asked whether there might be a correlation. In a recent study, our results suggest that stress produces changes in growth and virulent-associated transcriptional patterns in selected stress-responsive indigenous bacterial communities. Certain white blood cells began to recognize indigenous bacteria as intruders transformed into more aggressive lymphocytes in order to attack them. This may jeopardize the normal tolerance to healthy tissue and increase the risk in individuals with a genetic predisposition to develop autoimmune disorders.
Dr. Hava Gil-henn
Cancer Metastasis Analysis and Treatment
Prior to joining Bar-Ilan University’s School of Medicine in 2011, Dr. Hava Gil-Henn performed two postdoctoral fellowships at the Yale University School of Medicine. She served her first fellowship in the Pharmacology Department exploring signal transduction. For her second fellowship, Dr. Gil-Henn joined the Molecular Biophysics and Biochemistry Department where she focused on the molecular mechanisms of cancer metastasis. Dr. Gil-Henn also spent one year as a visiting scientist at the Albert Einstein College of Medicine, focusing on the in vivo mechanisms of cancer metastasis.
Dr. Gil-Henn and her team use a combination of molecular biology, cell biology, high-resolution imaging, proteomics, genomics, structural biology, and in vivo models of cancer metastasis to identify the proteins and signaling pathways that contribute to cancer’s ability to invade healthy tissue and the process of becoming metastatic. Her goal is to use this information to develop diagnostic, prognostic, and therapeutic approaches to cancer.
Primary tumors are responsible for only a small percentage of cancer deaths and can often be removed without further relapse. The complications associated with distant metastasis, however, are the primary cause of cancer mortality. Most cancer treatments attempt to shrink or slow tumor growth, but no treatment exists at present that permanently eradicates metastasis.
A better understanding of the molecular, cellular, and physiological conditions that initiate metastasis are valuable for identifying and improving outcomes of patients who suffer from metastatic cancer.
“Our work aims to develop a method for identifying the tumors that have increased likelihood to disseminate and to tailor anti-metastatic therapeutic intervention that is specific for the particular patient,” says Dr. Hava Gil-Henn. “We aim to use the information gained in our studies in order to develop both diagnostic and prognostic tools for assessing the metastatic potential of specific tumors, as well as new therapeutic tools to block cancer metastasis.”
Dr. Gil-Henn’s laboratory has identified several novel approaches, and her team is now testing these on patient tumor samples with the long-term vision of offering more effective diagnoses and therapies for cancer patients in Israel and worldwide.
Annual Activity Report, March 2017 - Development of diagnostic, prognostic, and therapeutic tools to block breast cancer metastasis
Our work aims to 1) develop a method for identifying cancer tumors that have an increased likelihood of spreading to other parts of the body, and 2) to tailor anti-metastatic therapeutic intervention based on unique genomic qualities in the patient’s DNA and tumor.
Research in our laboratory uses a combination of molecular biology, cell biology, high-resolution imaging, proteomics, genomics, structural biology, and in vivo models of cancer metastasis in order to elucidate the proteins and signaling pathways that contribute to the tissue invasiveness and metastatic potential of cancer cells. We are aiming to use the information gained in our studies in order to develop both diagnostic and prognostic tools for assessing the metastatic potential of specific tumors as well as new therapeutic tools to block cancer metastasis.
Dr. Evan Elliott
Molecular and Behavioral Neuroscience
Dr. Elliott is a founding faculty member of the Bar-Ilan School of Medicine, which opened its doors in 2012. Dr. Elliott and his team conduct genome-wide scans and behavioral studies with mice. His research is important to the Dangoor Centre for Personalized Medicine for its emphasis on genetic profiling and big data computation.
There are two major goals of the Molecular Neuroscience laboratory:
1) To determine molecular mechanisms that are involved in the development and etiology of Autism Spectrum Disorders.
2) To understand the roles of epigenetics in molecular processes in the brain.
These goals are being pursued using multiple tools and techniques, including postmortem studies and the behavioral and molecular analysis of multiple autism mouse models.
Dr. Elliott also delivers a course he developed, entitled “Brain and Mind”, to Bar-Ilan University medical students. The course focuses on the relationship between neuro-anatomy and behavior, including disease.
Dr. Elliot has won prestigious grants from the Israel Science Foundation, the German-Israeli Foundation for Scientific Research and Development, and the Israel Psychobiology Foundation. He has also published in the top journal Nature Neuroscience. Dr. Evan Elliot earned his MSc and PhD at Weitzman Institute. In an exciting new project, his lab is establishing a national autism patient registry, whose goal is to improve Israeli autism research through a registry which will gather information about the epidemiology of autism in Israel and the establishment of a tissue bank for autism research.
Annual Activity Report, March 2017 - Autism biobank and personalized medicine program
Within the past year, the autism biobank and registry program has made various strides towards our long term goal of biomarker identification and patient stratification. Our team has started the process of building a registry of individuals diagnosed with autism who are willing to take part in future autism research programs, and to collect their blood, stool, and saliva samples for our autism biobank. This biobank will be open for all autism researchers. Our laboratory will perform microbiome and immune system characterization of these samples to perform stratification and to understand the biological basis of autism.
We have begun recruiting families with individuals diagnosed with autism, and currently have recruited approximately 25 families, including the collection of biological samples, which have been placed in our biobank. We are now continuing our recruitment through Ziv hospital in Safed, and are now starting long-term collaborations with autism treatment centers in autism, with the goal of recruiting at least another 100 families within the next year.
In our laboratory, in collaboration with Dr. Omry Koren, preliminary analysis of the microbiome of individuals with genetic predisposition to autism has revealed changes in bacteria that play a very important aspect in human health. Therefore, within the next several years, we will work to verify these results in the samples which we are recruiting through our registry and biobank. Considering the real possibility of using probiotics in patients, it is not unlikely that our research will lead directly to new diet regimens or probiotic treatment in a subset of individuals diagnosed with autism.
Dr. Meital Gal-tanamy
Molecular Virology Laboratory
Dr. Meital Gal-Tanamy joined the BIU School of Medicine following two prestigious post-doctoral fellowships, the first in the Department of Virology and Immunology at the University of Texas and the second in the Felsenstein Medical Research Center at the Sackler School of Medicine in Tel-Aviv University. Her research at BIU focuses on developing a vaccine against the Hepatitis C virus (HCV).
Over 180 million people worldwide are infected with Hepatitis C virus (HCV), and this virus is a major cause of chronic liver disease and hepatocellular carcinoma (HCC). HCC represents the fifth most common cancer worldwide and the second cause of cancer mortality in males. Dr. Gal-Tanamy’s lab leads research that will contribute to a rational vaccine design against HCV through exploring the antibody response to this infectious agent. Meital’s lab also explores the changes that HCV causes to the structure of the genome, looking for those which are linked to the onset of liver cancer.
Additionally, Gal-Tanamy and her team evaluate the potential of epigenetic drugs to stop the progression to cancer by reversing the changes made by HCV to the genome. This work will attempt to harness knowledge of cancer origin to determine effective treatment. Her laboratory works in cooperation with Beilinson Medical Center and BIU affiliated hospitals in Nahariya and Tzefat.
The strategies employed by Dr. Gal-Tanamy and her researchers should prove helpful in preventing and treating HCV-related liver disease, a major milestone in the long battle against this virus and related diseases.
Annual Activity Report, March 2017 - The interplay between epigenetic and genomic signatures of Hepatitis C virus in hepatocellular carcinoma
Through epigenetic analysis, we have unraveled both known and novel pathways that are dysregulated by the Hepatitis C (HCV) and Hepatitis B (HBV) viruses. These epigenetic alternations leave a signature on the host chromatin that leads to the onset of Hepatocellular carcinoma (HCC).
We might be able to use the results of this study to predict an individual’s sensitivity to existing drugs, or to design prognostic assays for the early detection of HCC. Moreover, since epigenetic changes are potentially reversible, this research may open new avenues to revert the oncogenic effects of chronic hepatitis infections and to prevent HCC.
Dr. Marcela V. Karpuj
Director, Genome Technology Center
Dr. Marcela V. Karpuj received her PhD in Neuroimmunology at the Weizmann Institute of Science after concentrating in Chemistry and Biochemistry for her BSc and MSc at the Hebrew University.
She leveraged her scientific background with the addition of an MBA from Presidio Graduate School in San Francisco, CA, and has done post-doctorate work at Stanford University and the UC-San Francisco. Her research has led to a potential therapy for Huntington’s disease which is currently undergoing phase II-III clinical trials.
Dr. Karpuj brings to the Dangoor Centre great deal of collaborative, teaching, and research management experience in business and academic environments, including Buffalo University, University of California, and Hebrew University.
As Director of the Genome Technology Center, Dr. Marcela Karpuj works closely with the researchers of the Dangoor Centre for Personalized Medicine to develop the proper sequencing protocol for the data they require.
Annual Activity Report, March 2017 - Significant Developments at the Genome Technology Centre
1. We have developed a collection of genetic libraries that uniquely facilitate the optimization of QA/QC processes, which positions us to provide the highest yield and quality of data.
2. We are now working to upscale our capacity by automating the library preparation process, including training to modify the protocols of our new Bravo Option B robot.
3. We developed a new system that enables the simultaneous processing of 48 samples at a time using the Fluidigm Access array system.
4. We have developed the Nanostring technology, which enables us to validate Illumine sequencing data.
5. Additionally, we have developed a test to detect and eradicate mycoplasma bacteria in cell-lines. Once treated, researchers interested in genetic profiling can perform experiments without worrying about damage caused by mycoplasma.
Dr. Omry Koren
Microbiome Research Laboratory
Dr. Omry Koren is a former Research Associate at the Department of Microbiology at Cornell University in New York. He joined BIU's School of Medicine in the Galilee as a Senior Lecturer in 2014. At BIU, his research focuses on microbiology, microbiome and microbiotas.
Dr. Koren's main field of research is infectious diseases. He researches bacterial genome sequences to determine the relationship between human lifestyle, bacteriome repertoires, and human health problems such as obesity and diabetes.
He is also doing research to help patients suffering from multiple sclerosis. On. In the near future, Dr. Koren will being collaborating with doctors at Bar-Ilan’s affiliated hospitals in the Galilee who are treating MS patients.
“Our lab studies the microbiome in health and disease. We are interested in how changes in the microbiota affect the health of the host and how we can control these changes for our benefit.” Koren’s research is aimed at elucidating the mechanisms behind environment-by-host–by-microbiome interactions. This research lends itself to many potential applications and collaborations at the Dangoor Centre for Personalized Medicine.
Dr. Omry Koren has recently received the prestigious Minerva Award for Research Cooperation and High Excellence in Science (ARCHES),the Marie Curie Career Integration Grant, and grants from IHEL – The Londrina Hematology Institute, and Israel’s Ministry of Health. He earned his MSc and PhD in Molecular Microbiology and Biotechnology at Tel-Aviv University.
Annual Activity Report, March 2017 - Polycystic ovary syndrome, diet and the microbiome
The polycystic ovary syndrome (PCOS), consisting of anovulation, is the leading cause of infertility and affects up to 10% of reproductive age women.
Working hypothesis and aims: We hypothesize that women with polycystic ovary syndrome (PCOS) have an altered microbiota compared to normal ovulatory women and that a low-carbohydrate diet will positively alter their gut microbiota leading to improvement in their overall symptoms and fertility. Therefore, we aim to characterize the microbiome of normal and overweight healthy, PCOS untreated, and PCOS diet-treated women and to test whether the diet intervention affects symptoms and health. We further aim to perform fecal transplants from all study groups into germ-free mice in order to show a causal effect between the microbiome and health outcomes, as well as test the metabolomics profiles of each group. Outcomes of this research will likely lead to improvement of current treatments for PCOS in overweight as well as normal weight women, and to an understanding of the roles of gut microbiota composition in PCOS.
Results: While we are still in the process of recruitment and sample collection, we have to date tested and analyzed the microbiota of a sample group of control vs. PCOS subjects (PCOS subjects including a sample from before intervention and after the diet intervention), and found distinct differences between groups. With the analysis of the full study group we hope to show that these differences are statistically significant and perhaps detect additional differences between groups.
Dr. David Enshell-seijffers
Stem cells in personalized medicine
Stem cell therapy is considered to be the leading potential methodology to cure a variety of devastated diseases currently lacking treatment. However, while the intrinsic properties of stem cells are under intensive study, the comparatively rudimentary understanding of the role of the microenvironment in regulating stem cell behavior has been an impediment to effectively integrating in vivo and in vitro studies to exploit the therapeutic potential of adult stem cells. Furthermore, stem cell exhaustion is considered one of the key factors causing aging. Therefore, understanding the mechanisms that maintain stem cell number and function in adult tissues may also provide methodologies to slow the process of aging. However, the variation in the genetic make-up of different individuals will require to fine tune these novel methodologies to tailor the treatment to the patient. Our research uses the hair follicle as a model system to study the molecular interactions between the stem cells and their environment. We use sophisticated genetic screens in mice and exploit the accessibility of the hair follicle to reveal genetic networks that regulate stem cell activity. The identification of such networks will enable us to develop molecular modifiers that can be applied to test their effect on curing different diseases and slowing aging. This requires the development of animal models. Therefore, we will establish embryonic stem cell center with the aim to design and generate transgenic animal models for a variety of diseases such as neurodegenerative diseases, cancer, autoimmunity and diabetes.
Annual Activity Report, March 2017
Prof. Farid Nakhoul - Single-nucleotide polymorphism (SNPs) in the autophagy-related gene 5 (ATG5) in patients with Diabetic Nephropathy & Retinopathy
The current study's aim is to evaluate whether or not a specific polymorphism (functionally silent difference) in the ATG5 gene is associated with diabetic renal and retinal diseases. Any day now, we should be receiving the final certification from the Helsinki Committee (medical research ethics committee) for this study. We are also reviewing the various DNA extraction kits, to find the optimal kit for our needs, so we can start calibrating our experimental system.
Prof. Jamal Zidan - Comparison of expression of breast cancer biomarkers in primary biopsies and in surgically resected tumors following neoadjuvant chemotherapy
Breast cancer patients usually undergo a core-needle biopsy (CNB) to determine the course of treatment. If the biopsy reveals the expression of certain biomarkers (namely, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2), and Ki67), then neoadjuvant chemotherapy (NAC) is indicated prior to surgical removal of the tumor. According to the medical literature the expression levels of these detective factors can change after NAC. We set out to measure these changes in our study, and the results may affect the choice of chemotherapy regimen the patient is given after surgery.
Dr. Andrei Braester, MD - Structural and Functional Characterization of Complement Components in Chronic Lymphocytic Leukemia Patients undergoing Immunotherapy
Dr. Andrei Braester, MD, Director, Institute of Hematology, Galilee Medical Center
Co-Investigator: Regina Michelis, PhD.
Researcher, Institute of Hematology, Galilee Medical Center
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. For treatment, clones of genetically designed white blood cells are used to trigger the body’s complementary immune system to target the cancer. Such an approach is called “complement-mediated cytotoxicity” (CDC). We wanted to study the structure of circulating complementary immune complexes and document the importance of their structural integrity for triggering an immune system attack during immunotherapy in patients with CLL.
Preliminary results indicate differences in the structure of complement complexes C4 and C5 in more than 50% of CLL patients, as well higher basal activity levels (indicated by C5b-9) as compared to healthy control subjects (HC). We have also documented that patients treated with aggregated IgG showed lower CDC responses than those treated with Zymosan. This indicates a possible link between the activation potential of the complement system in CLL patients and structural alterations in the C5 complex. It also suggests that developing a marker to detect changes in the C5 complex may assist clinicians in refining and personalizing the immunotherapeutic approach, improving CDC and consequently the therapy results.
Dr. Armaly Zaher - Impact of Haptoglobin Genotype on Intravenous Iron Administration-induced Oxidative Stress and Inflammatory response in Patients with Chronic Kidney Disease (CKD)
Background: Anemia is a common problem in CKD patients. It is attributed to decreased erythropoietin (EPO) production, low iron stores, and accompanying chronic inflammation. Therapy includes infusions of recombinant EPO to help boost erythropoietin production and also iron replenishment. However, treatment produces side effects, namely oxidative stress and inflammation, which are especially high in certain patients. L-carnitine supplementation has been used to mitigate these side effects in long-term dialysis patients. We were interested in how such supplementation would benefit early stage CKD patients. Furthermore, some patients have a variant form of haptoglobin, which protects the body by binding to and neutralizing loose hemoglobin in the bloodstream, which can cause kidney damage. We wanted to document the effect of this genetic variant on oxidative stress in CKD treatment.
Results: We found that combined administration of IVIR and carnitine brought about increased hemoglobin (Hb) levels in those subjects relative to subjects who received IVIR alone. Also, IVIR alone induced oxidative and inflammatory responses, but patients who received carnitine did not exhibit these adverse effects. These results were most profound in patients with the Hp2-2 variant of haptoglobin.
Conclusion: Our findings indicate that co-administration of carnitine with IVIR preferentially attenuates the adverse consequences of IVIR and suggests a role for carnitine therapy in these patients. Moreover, this study demonstrates that Hp2-2 is a significant risk factor for IVIR-induced oxidative stress in CKD patients.
Dr. Khaled Khazim and Dr. Cohen Idan - Genome-wide transcriptome profiling of circulating neutrophils in patients with end stage renal disease
In this research proposal we aimed to try and understand the underlying mechanism(s) of circulating blood neutrophils activation in ESRD patients using a full transcriptome analysis profiling. Our major goal was to try and uncover cellular mechanisms that will potentially lead to a better understanding of this process and may discover novel therapeutic targets for treatment or intervention. Additionally, by doing so, we hoped to discover a single "factor" of these cells that may be later used as a "biomarker" for assessing and monitoring atherosclerosis initiation and progression. We are happy to report that the mutual efforts of Dr. Idan Cohen, Din Richtert (the MD project student from the Faculty of Medicine) and I have already yielded 2-3 strong factors that play a pivotal role in neutrophils biology and can be used as potential biomarkers, including Hypoxia-inducible factor 1-alpha (HIF-1a), and Sirtuin 1 (SIRT-1).
Dr. Maya Wolf, MD - Fetal and maternal hormonal and signaling molecule association with outcome of labor induction
This study is a comparative evaluation of the correlation of fetal and maternal labor-associated hormones and signaling molecules between two methods of induction of labor in women with previous cesarean section. Collaborators are: Maya Wolf, MD, Department of Obstetrics & Gynecology, Galilee Medical Center, and the Faculty of Medicine, Bar-Ilan University, Israel; Jacob Bornstein, MD, MPA, Professor (PI) Department of Obstetrics & Gynecology, Galilee Medical center, and the Faculty of Medicine, Bar-Ilan University, Israel; Dr. Eilam Palzur – Research lab, Galilee Medical Center, Nahariya, Israel; Dr. Mona Shehada – the biochemistry lab, Galilee Medical Center, Nahariya, Israel
To date, 42 women have joined the study. The study aims include 60 women. The women were randomly divided into two groups: those who undergo induction of labor by balloon catheter or those who undergo breast stimulation. Blood samples for the analysis of hormone and signaling molecule levels were drawn at time 0, 3 and 6 hours from commencement of labor induction. In addition, immediately after delivery, cord blood was tested for those hormone and signaling molecules levels, and for bilirubin and cord pH. All samples are marked and preserved for later testing. Enrollment is expected to reach completion in two months, at which time all the samples will be processed and analyzed together, to ensure uniform laboratory conditions.
Prof. Offer Amir - miRNA in Acute Coronary Event: pathogenesis and risk stratification
Below is a brief progress report on our study of miRNA and its role in acute coronary events. Our study is aimed at providing ways of using miRNA to predict the onset of cardiac arrest and to identify an individual’s risk level for experiencing such an event.
We have optimized and adjusted the protocol for isolating blood components to our experimental settings, and performed a small pilot study. More than 300 patients have been recruited to the study so far. Blood samples were collected and processed. miRNA from 72 platelets samples was isolated and prepared for NGS. miRNA were sequenced on the HiSeq Illumina machine by Genomic Unit in the Faculty of Medicine, Safed. Bioinformatics analysis following the NGS was performed. Several miRNA were identified as differentially expressed. We intend to validate our findings using larger patient cohorts and a different experimental technique. We have chosen to use quantitative Real Time PCR (qPCR). So far we have optimized all steps of this procedure and adjusted for our experimental settings. To identify stable molecules suitable for our study, a NormFinder program was applied, with our NGS data used as an initial input.
Dr. Hadassah Goldberg & Dr. Rona Fell - Isolation and characterization of potentially metastasizing tumor cells from primary breast cancer samples
This is an interim report concerning a study funded by the Dangoor Foundation, 2016-17. The study is aimed at isolating breast cancer cells that harbor the potential to form distant metastases from primary tumors.
Our study is based on fresh tumor samples, which must be processed immediately after the surgical removal of the tumor. Therefore the entire study platform must be operative prior to initiation of sample collection. Up to now, we have completed the following steps:
1) We have constructed the method for tissue separation into a single cell suspension. 2) We have acquired the means necessary for removing blood stem cells from the total cell mixture. 3) We have conducted a comprehensive survey of the literature and selected the antibodies for separating the cell suspensions into two groups: metastasizing tumor cells (identified by markers of the ‘epithelial to mesenchymal transition’ (EMT) process), and non-metastasizing cells. This will be done using the Beckman Coulter MoFlo Astrios located at the Faculty of Medicine, Bar-Ilan University. 4) We have ordered the antibodies for removing stem cells. Once they arrive, we will start collecting tumor samples and begin the study. 5) We are grateful for the cooperation of Breast surgeon Dr. Assi Drobot and Pathologist expert Dr. Liat Appel from the Galilee Medical Center. Dr. Drobot has also agreed to present the study to the patients and ask them to sign an informed consent prior to their surgery.
Prof. Eitan Okun
The Mina and Everard Goodman Faculty of Life-Sciences
Learning, memory and neurodegenerative disorders
Prof. Eitan Okun has conducted his Post-doctoral fellowship with Dr. Mark P. Mattson at the Neuroscience laboratory at the National Institute of Aging, National Institutes of Health. He then moved on 2012 to a senior lecturer position at Bar Ilan University, where as of 2017 he is an associate Professor.
Prof. Eitan Okun is heading the Paul Feder research laboratory on Alzheimer’s disease research at the Mina and Everard Goodman faculty of life sciences. He is also affiliated with the Gonda Multidisciplinary brain research center at Bar Ilan University.
Age-related neurodegenerative diseases, Alzheimer’s disease chief amongst them, are currently incurable due to several critical reasons, such as the lack of early diagnosis capabilities, or the apparent heterogeneity between patients. The latter in-fact calls for the development of personalized medicine tools and approaches. As a result of that, our laboratory is focused on the following research directions:
- Developing a biomarker for an earlier diagnosis of protein-aggregation diseases such as Alzheimer’s and Parkinson’s disease using magnetic resonance imaging (MRI). As different patients exhibit different pathology severities, that are differentially spread throughout the brain, It is critical to develop a biomarker that will provide information on both aspects of this pathology to devise appropriate treatment.
- Developing vaccination strategies that target Amyloid beta. This is done in both Alzheimer’s disease models as well as in Down-syndrome models which exhibit Amyloid-beta related pathology.
- Assessing causal and correlational links between Down-syndrome and Alzheimer’s disease.
Another line of research in our laboratory aims to understand the mechanism(s) behind the beneficial effect of aerobic exercise on cognitive learning and neurogenesis. We use various cognitive tasks and precise measurements of the formation of new neurons in the brain to understand what is the mechanism behind aerobic exercise, in an effort to translate findings to cognitive enhancement.
Prof. Cyrille J. Cohen
The Mina and Everard Goodman Faculty of Life-Sciences
(Bridging between personalized medicine and Immunotherapy)
The recent progress in genomics and other diagnostic technologies have contributed to the emergence of personalized medicine. Concomitantly, we are witnessing the rise of immunotherapy, a kind of biological therapy, now applied to treat a variety of diseases and especially cancer. It is designed to generate, promote and or enhance the action of the body's natural defenses/immune system to fight pathogens or cancerous tumors. Nevertheless, cancer cells may escape from immunotherapy using a broad spectrum of mechanisms and as for every treatment, we come to realize that the patient genetic and physiological backgrounds can greatly influence prognosis and treatment outcome.
With this in mind, Prof. Cohen’s group at Bar-Ilan University specializes in the study and the engineering of the immune response of T and NK lymphocytes against cancer while taking into account patient features such as immunological genetic background and specific antigen expression. Prof Cyrille Cohen has been involved in immunology research for the past 20 years and trained at the National Cancer Institute, NIH, US for 4 years before establishing the laboratory of tumor immunology and immunotherapy at Bar-Ilan University in 2007.
He and his group developed a robust research expertise that encompasses molecular biology, computerized predictions and analysis, immune and cancer cell techniques including studies animal models and collaborations with medical centers in Israel and abroad. They recently demonstrated for the first time the presence of neo-antigen specific T-cells in the blood of several advanced melanoma patients and developed a strategy to isolate these cells. Interestingly, while these patients displayed similar disease progression and symptoms, they showed that the anti-tumor immune reaction was unique to each patient/tumor studied.
Moreover, they are interested in developing approaches that would more accurately predict immune cell reactivity based on cancer patient genetic background. Additionally, they focus on elaborating strategies to generate sets of targeting molecules that will fit, in a personalized way, tumors from individual patient using recent gene transfer and receptor strategies they developed. Also, they are studying the role of individual mutations in tumor antigens and their influence on the anti-tumor response in several kinds of cancer. In collaboration with Prof. Rachela Popovtzer (Fac. of Engineering, BIU), they have been developing theranostic approaches based on gold nano-particles coated with immune activators and checkpoint inhibitors to rapidly (within 48 hours) stratify treated subjects into responders or non-responders, which could further help in custom-tailoring future patient treatment.
Overall, bridging between personalized medicine and immunotherapy, now more than ever before, will lead to more precise and efficient cancer therapy.
Prof. Ilanit Hasson-ohayon
Department of Psychology
Psychological aspects of personalized medicine and personalized psychological services
Prof. Hasson-Ohayon from the department of psychology in BIU, conduct studies in the field of rehabilitation psychology, mostly in the topic of psychiatric rehabilitation, psychooncology and grief. She completed her PhD at BIU on the topic of psychiatric rehabilitation and did a post-doc in Hadassah medical center in the psychooncology unit. She works both as a researcher and as a clinician in the field of rehabilitation psychology.
Her studies address the coping processes of people and families with illnesses and the possible benefits of psychological treatments. The idea of personal tailored treatment is of major relevant in her studies and highlighted in the publications of studies from her lab. Specifically, in interventional studies she examines the personal characteristics that serve as mediator or moderator for outcome. She also studies communication patterns between patients and medical staff )in psychiatry and oncology) and the need to tailor interventions according to personal characteristics and shared decision making processes.
Dr. Ron Piran
The Azriely Faculty of Medicine
Pancreatic β-cell regeneration, stabilization and protection in pre-diabetic and diabetic patients
Ron Piran earned his Ph.D. from the Technion in Israel. His decision to devote himself to efforts to find a cure for diabetes evolved out of experiences during his Ph.D. training, which focused primarily on theoretical computer science and formal logic. Using an algebraic modeling method of embryonic development, Dr. Piran predicted and proved the existence of a new biochemical pathway. Dr. Piran took his approach to the Levine lab at SBP, La Jolla CA, where he successfully obtained the prestigious CIRM Fellowship. He studied β-cell regeneration following pancreatic damage. He used his algebraic model to develop new β-cells from α-cell conversion – an important new pathway for β-cell neogenesis. Dr. Piran made major progress in understanding the molecular mechanism by which that process occurred, and isolated a druggable cell receptor, which holds promise for clinical application.
All type I and some type II diabetes patients are suffering from the loss of the insulin expressing b-cells. Therefore, b-cell regeneration has garnered great interest as an approach to personalized diabetes therapy. We developed a model of pancreatic damage, combining pancreatic duct ligation with b-cell ablation, which led to the induction of a novel pathway for b-cell neogenesis in which a-cells from preexisting islets transdifferentiated into neogenic b-cells. Using a candidate approach, we identified the PAR2 receptor as having properties that could play a role in the transdifferentiation process. To test that idea, mice had their β-cells ablated and were injected with PAR2 agonist. A similar experiment preformed in PAR2 knockout (PAR2KO) mice has shown no regeneration of b-cells. The finding of efficient a- to b-cell conversion raises the prospect that b-cell regeneration may be feasible. Caerulein injected to PAR2KO mice led to specific b-cell death. Selective b-cell loss is a cardinal feature of T1, and also occurs in T2. This supported the hypothesis that PAR2 is a key mediator of b-cell death in diabetes. The mechanism by which b-cells are destroyed without affecting a- or δ-cells, which are related in terms of location, development, and gene expression, is not understood. To our knowledge, this is the first example of a single gene capable to mediate selective b-cell death in response to an external trigger. Using a commercial C-peptide assay, we will recognize the diabetic and pre-diabetic patient individuals that suffers from β-cell loss. Then, we will stabilize β-cells in these patients and by using PAR2 modulation to regenerate them in β-deficient patients that already developed diabetes.
Prof. Shimon Weiss
Department of Physics
Nanovoltage sensors for brain research
Shimon Weiss received his PhD from the Technion in Electrical Engineering in 1989. After a one year post doctorate at AT&T Bell Laboratories, he joined Lawrence Berkeley National Laboratory as a staff scientist in 1990 where he re-directed his interest to single molecule biophysics. In 2001 he joined the UCLA Chemistry & Biochemistry and the Physiology departments. In 2016 he also joined the Physics department at Bar Ilan University, Israel (part time). The Weiss lab has been working on ultrasensitive single molecule spectroscopy methods. They were the first to introduce the single molecule FRET method and quantum dots to biological imaging. They have also developed a variety of single molecule spectroscopy methods and the SOFI superresolution imaging. Currently they are developing single inorganic nanoparticle voltage sensors for probing neural networks. They have been interested in regulation of transcription initiation (bacterial RNAP and human pol-II). Dr. Weiss has published 166 peer-reviewed papers, and holds 32 issued and 35 published patents. He was awarded the Humboldt Research Award, the Rank Prize in opto-electronics, and the Michael and Kate Barany Biophysical Society Award. He holds the Dean Willard Chair in Chemistry and Biochemistry and he is a Fellow of the Optical Society of America.
Personalized Medicine Activity:
Voltage sensing nanoparticles (vsNPs) that self-insert into the cell membrane could optically record, non-invasively, membrane potential at the single-particle and nanoscale level, at multiple sites, in a large field-of-view. vsNPs could be applied for neurodegenerative disorders in the CNS (e.g. PD, spinal cord injury, psychiatric disorders), PNS Diseases (e.g. ALS, MS, MD, IBS, AMD, Huntington, Chorea, Neuropathy, etc.), Retinal neurons (ophthalmology, diabetic neuropathy) and Vagal Afferent/ Efferent AP detection and stimulation. In addition to neuronal cells, a distinct voltage sensitivity and voltage-dependent activity is known for cardiomyocytes, cancer cells, and β cells islets. The putative voltage disturbance in pathological states may be translated into precise characteristics and personal diagnosis in order to match personalized treatment per disease stage for cardiovascular diseases, cancer and diabetes.
Prof. Bilha Fischer
Department of Chemistry
Medicinal Chemistry Laboratory
With 110 peer-reviewed articles and 12 patents to her name, Prof. Fischer leads a medicinal chemistry laboratory at the department of Chemistry, BIU. She is an alumnus of Bar-Ilan and has served in a variety of leadership positions within the university as well as national and international positions. She has won several prizes including the Teva Prize for excellent young scientists, the Juludan Prize for the Application of Exact Sciences to Medicine, and was selected as one of 50 most influential women for the year 2014 (Globes magazine).
Prof. Fischer believes that nature is economic, efficient, and elegant. Indeed, a limited number of small molecules play numerous functions in life. Therefore, in her research she has selected natural mononucleotides, di-nucleotides, nucleoside-bisphosphates, and oligonucleotides as scaffolds for the development of innovative building blocks and novel drug candidates. Those new molecules were applied for diagnosis and drug development (treatment of type 2 diabetes, glaucoma, Alzheimer’s disease, inflammatory bowel diseases, osteoarthritis, and innovative siRNAs for silencing gene expression).
Together with Prof. Yaron Shav-Tal (Life Science Faculty), Prof. Fischer develops probes for diagnosis of subtypes of breast cancer towards personalized medicine. Since current methods of molecular-level breast cancer diagnosis toward personalized medicine are less than optimal, they target the development of innovative oligonucleotide (ON) and peptide nucleic acids (PNA) probes to detect breast cancer mRNA markers for the identification of breast cancer subtype.
The probes incorporate fluorescent intercalators, inspired by naturally occurring fluorescent molecules. To obtain a useful fluorescent probe that has an excellent signal/ background ratio and also excellent brightness, the Fischer group synthesizes various chromophores covalently bound to a nucleoside or PNA via a flexible spacer. These nucleosides are incorporated into ss-ON/PNA probes targeting specific mRNA markers. Targets include HER2, BRCA1/2, ER, and PR mRNA breast cancer markers, tested in live cells by the Shav-Tal group. Ultimately, they target the application of these probes to patients’ biopsies. This project serves as a stepping stone toward the diagnosis of breast cancer sub-type in patients and toward personalized medicine.
Prof. Orit Shefi
The Alexander Kofkin Faculty of Engineering
Nanoengineered personalized platforms for neuronal regeneration
Orit Shefi is an Associate Professor in the Faculty of Engineering, head of Neuro-engineering and Regeneration laboratory and a member of the Institute of Nanotechnologies and Advanced Materials. She has joined Bar Ilan after completing her Ph.D. in Physics from Tel-Aviv University, and after postdoctoral studies in Neurobiology at University of California, San Diego.
Prof. Shefi’s team is developing holistic solutions to nerve injuries with specific personalized design. These include engineered platforms to be implemented in the injured site and delivery methods of therapeutic agents to specific target sites following pathologies mapping.
Nerve injuries, often as a result of blunt trauma or neuroma, cause loss of motor and/or sensory functions and degenerative effects, arising the need for effective clinical treatments. Damage is not just to patients but also to community. Many efforts are devoted to advance solutions. In the lab we develop personalized platforms for peripheral nerve injuries. In nerve injuries, axon continuity is disrupted or completely loss, and in many cases surgical intervention becomes necessary. Current solutions include direct repair and graft repair techniques. We have developed a promising strategy of using artificial nerve guidance conduits (NGC) which aims to guide the regenerating nerves to their intended target implanting new materials, synthetic or natural based, to provide support for optimal regrowth. Our NGCs mimic the natural composition and structure of specific nerve tissue. We develop ways to implant a conduit by injection of a solution, than controlling its shape and internal structure according to the specific needs. Our approach allows in-site treatment to be integrated with the unique characteristics and needs of the patient. Currently we extend the platform by examining the incorporation of stem cells into the engineered platforms (autologous or allogeneic).
To improve repair efficiency we study novel strategies for targeted drug delivery. With a method we recently have developed we can inject drugs systemically and treat pathologies locally. We functionalize NPs, having a ‘smart’ delivery system of biomolecules, together with integral guidance cues. We have shown accumulation of drugs in specific areas in the central and peripheral nervous system.
We aim to enhance the therapeutic potential of the platforms and to translate them into practice to allow better personalized solutions for neuronal repair.
Dr. Nissan Yissachar
Intestinal neuro-immune-microbiome cross-talks, in health and disease
The Mina and Everard Goodman Faculty of Life Sciences
Dr. Nissan Yissachar joined the Faculty of Life Sciences at Bar-Ilan University in 2017 following two post-doctoral fellowships, the first at the Weizmann Institute of Science and the second at Harvard Medical School. His lab at BIU investigate the interactions between the intestinal immune system, the enteric nervous system and the gut microbiota, in health and disease, aiming to develop a microbiome-based, personalized therapy for human inflammatory diseases.
To study these complex neuro-immune-microbiome interactions in the lab, Dr. Yissachar developed a novel organ culture system for the mouse intestine. This unique approach led him to discover that enteric neurons mediate specific immunological effects of the human gut microbiome. In the future, these investigations may result in new therapeutic approaches to autoimmune diseases (such as type-1 diabetes and rheumatoid arthritis), chronic inflammatory diseases (such as crohn’s disease and ulcerative colitis) and cancer.
Dr. Ayal Hendel
A CRISPR Approach to Precision Medicine
The Mina and Everard Goodman Faculty of Life Sciences
Ayal Hendel is a Principal investigator and a Senior Lecturer in the Mina and Everard Goodman Faculty of Life Sciencesin at Bar-Ilan University. Ayal’s research focuses on developing Genome Editing and the CRISPR technology as a method of gene therapy for genetic diseases of the blood and the immune system such as severe combined immunodeficiency. In addition, Ayal's lab develops novel genome editing approaches for cancer immunotherapy. Ayal received his B.A. with high honor from the Hebrew University of Jerusalem in Biology and his M.Sc. and Ph.D. from the Weizmann Institute of science. Ayal carried out post-doctoral research at Stanford University School of Medicine with Prof. Matthew Porteus, where he demonstrated that chemical alterations to synthesized CRISPR-single guide RNAs enhance genome editing efficiency in human primary T cells and hematopoietic stem and progenitor cells. In addition, in a recent study he was part of a team that achieved therapeutically relevant genome editing frequencies in human hematopoietic stem and progenitor cells.
We are in the midst of a revolution in genome editing and CRISPR-Cas9 technology was the spark. With unprecedented rapidity, the discovery of clustered, regularly interspaced, short palindromic repeats (CRISPR), and the CRISPR-associated protein 9 (Cas9) has provided a straightforward, robust, and specific method for genome editing. Our lab is particularly interested in applying genome editing for personalized medicine and gene therapy of genetic diseases of the blood and the immune system such as primary immunodeficiencies and cancer. We believe that the ultimate cure for these diseases will be application of a genome editing approach where we precisely correct mutated genes while leaving the remainder of the genome with minimal perturbation. Therefore, our research focuses on developing genome editing as curative therapy for genetic diseases and improving genome-editing efficiency, specificity and safety in order to advance this technology towards treatment in patient.
Prof. David Karasik
Genetics of Age-Related Musculoskeletal Diseases
The Azrieli Faculty of Medicine
Prof. Karasik is a graduate of Tel Aviv University (Medical Sciences, 2000). He spent several years as a postdoctoral scientist in Harvard Medical School (Boston, MA). The primary objective of our research is to decipher the genetic variation of complex traits, including bone mass, muscle function, fatty liver, and biological aging. Our search for biological connections between the muscles and bones is aimed to inspire novel molecular strategies for the treatment and prevention of osteoporotic fractures, metabolic syndrome, sarcopenia (muscle wasting) and other devastating diseases.
Prof. Karasik was a senior author on the first genome-wide association study (GWAS) for fracture risk and contributed to multiple GWAS analyses of musculoskeletal aging-related traits. We actively participate in international consortia such as CHARGE, GEFOS, SUNLIGHT, and ReproGen. Our studies were published in leading journals such as JAMA, Nature, Nature Genetics, Nature Communications, Lancet etc.
Our recent efforts have focused on fine-mapping (by targeted sequencing) and functional follow-ups of the GWAS-identified loci. We are an integral part of the TransOmics for Personalized Medicine (TopMed, USA) and musculoskeletal working group of UK Biobank 500K analytics. We use molecular biology techniques in vitro and the zebrafish (Danio rerio, ZF) as an in vivo model for functional follow-up of the human associations. In parallel, we work on incorporating genetic risk scores for prediction of stress fractures in IDF soldiers and on exome resequencing in Druze sample from the Galilee (affected with metabolic syndrome).
Prof. Ronit Sarid
The Mina and Everard Goodman Faculty of Life Sciences
Ronit Sarid is a member of the faculty of Life Sciences. Her main research field is viruses and her training includes MSc and PhD studies at Tel Aviv University on lentiviruses and retroviruses, and two post-doctoral fellowships on different human herpesviruses. Her current research focuses on human herpesvirus 8, also termed Kaposi’s sarcoma-associated herpesvirus (KSHV), and on the development of novel nanoparticle-based antiviral therapies.
KSHV is etiologically linked to all types of Kaposi's sarcoma (KS), which is known as angiogenic and inflammatory cancer. KSHV is a prerequisite for KS, yet most KSHV-infected individuals never develop KS suggesting that additional factors affect the risk of KS development. Risk factors for the disease are not yet clear, though it has been established that active virus replication and high viral loads are required for the onset of KS. Of note, few cases of familial clustering of KS were documented suggesting that genetic susceptibility to KS, together with KSHV infection, might explain the development of the disease.
The Sarid lab studies different aspects of KSHV infection, including functional characterization of selected viral genes, host-virus interactions, depiction of cellular alterations that take place during virus infection and identification of signaling pathways that participate in the control of the infectious cycle. These studies are expected to identify host factors and gene variants that potentially promote the development of KS. Her studies are expected to reveal new regulators and mechanisms which govern KSHV infection and disease development. A similar strategy can be applied to screen for host genes that regulate other viral infections.
Dr. Milana Frenkel-Morgenstern
Liquid Biopsy Platform for Early Diagnostics of Brain Tumors
The Azrieli Faculty of Medicine
Dr. Frenkel-Morgenstern is a systems biologist with a coherent career leading to excellence in extracting the maximal capabilities in a wide variety of molecular & computational tools. She remained focus on creative improvements in the interphase of large scale data and personalized diagnostics. Her background knowledge is in computational and molecular biology, cancer genomics and transcriptomics. Currently, she has integrated two labs under her supervision: Computational Biology lab (equipped with 4 Dell ultra-large memory servers and 1PetaByte storage) and a wet Molecular Biology & Cancer Genomics laboratory. Her team has the skills to bridge the gap between hundreds of thousands of parameters studied in the laboratory or by computational biology and deliver reliable platforms answering specific clinical questions that remain unmet. Her labs are utilizing various sequencing methods to uncover unique genomics, epigenetics and metagenomics characteristics in vitro as well as analysing tissue and blood samples from cancer patients for Personalized Medicine approaches. During her first postdoctoral study at Prof. Uri Alon's lab, Weizmann Institute of Science, she gained a substantial expertise in Systems Biology. During her second postdoc at Prof. Alfonso Valencia's lab, Spanish National Cancer Research Centre (CNIO), she studied Cancer Genomics and chimeric transcripts in different cancer types. She solved the problems in genomics and cancer biology using theoretical models matched with empirical experimentation. She is particularly interested to study such naturally occurring phenomenon as trans-splicing and fusion proteins in cancers, as well as regulation of protein translation by transfer-RNAs during the cell-cycle, chimeric RNA transcripts and proteins, changes in protein-protein interaction networks by fusion proteins, single cell sequencing and cell-to-cell variability, personalized medicine and identification of novel diagnostic and prognostic biomarkers in cancers using circulating tumour DNA in plasma and by means of Liquid Biopsy. She generated data sets in vitro with high-throughput sequencing, proteomics, and single cell analysis, while in silico she has specialized in mathematical modelling and data mining to generate testable hypotheses using high-throughput datasets. During her academic career, she won several prestigious fellowships, the last one in 2011, the Miguel Servet (FIS) fellowship given for one only young scientists in the Hospital Carlos III (Madrid, Spain) by the FIS Foundation. She joined the BIU Faculty of Medicine in Galilee as an independent PI (tenure-track Assistant Professor/Senior Lecturer) in October 2014.
Dr. Amir Bashan
Diagnosis and personal treatments based on microbial ecology
Department of Physics
Dr. Amir Bashan is a Senior Lecturer at the physics department of Bar-Ilan University. He received his PhD in physics of complex systems from BIU under the supervision of Prof. Shlomo Havlin. He completed a post-doctoral fellowship in the Channing Division of Network Medicine at Harvard Medical School. In 2013, Dr. Bashan won the Israel Physical Society Prize for Best PhD in theoretical physics. In 2017, Dr. Bashan received the Faculty Fellowship of Azrieli Foundation for Outstanding Young Scientists.
The human gut microbiome is a home for trillions of microorganisms from hundreds of different types, which play a crucial role in determining our health and well-being. Unbalanced microbial communities are linked to diverse physiological disorders, such as inflammatory bowel disease (IBD), obesity, allergy and autoimmune diseases. Yet, restoration or even diagnosis of an unbalanced microbial community is challenging, mainly because these microbes live in a very complex dynamic ecological system, shaped by intense species-species and host-species interactions.
Recently, D. Bashan found that the gut microbial communities of healthy subjects follow consistent ecological rules (e.g. inter-species interactions) with a typical assemblage-to-abundance pattern. This new findings improve our understanding of the complex dynamics of microbial ecosystems and pave the way towards developing novel diagnosis and therapy methods.
We develop novel personalized therapeutic strategies based on microbial species interactions, that will steer an unhealthy microbiome of a patient to a new healthy state.
Our mission is to create a direct interface between theoretical ecology and medical practices. Considering the great concern due to the rising in antimicrobial resistance, ecological design of the human microbiome may be used as an alternative treatment for suppressing pathogenic infections in order to reduce unnecessary antibiotic administration.
Prof. Uri Nir
Stratifying cancer patients according to their potential response to anti-metabolic drugs
The Mina and Everard Goodman Faculty of Life-Sciences
Prof. Uri Nir leads the "Cancer and Inflammatory diseases" research lab in the Faculty of Life-Sciences at Bar-Ilan University, Israel. Between the years 2010-2014 Prof. Nir served as the dean of the Faculty. Nir gained his PhD degree from the Weizmann Institute of Sciences in Israel. He then went for a post-doctoral training in the "Hormone-Research Institute" at the University of California San-Francisco, CA., USA. Since 1988 Prof. Nir is a faculty member in the Faculty of Life-Sciences at Bar-Ilan University. The main research interest of the Nir's group is: Molecular biology of malignant processes and diseases and development of new anti-cancer compounds. These two disciplines are combined by us in order to identify tumor associated genetic susceptibility markers and factors which would stratify cancer patients according to their potential responsiveness to new anti-cancer drugs which selectively target the energy generation systems of cancer cells. This personalized-medicine approach should enable the rational selection of cancer patients for being treated with our newly developed anti-cancer compound-E260. This compound selectively targets the reprogrammed energy-generation power stations (mitochondria) of cancer cells, thereby leading to an energy crisis and necrotic death of the treated tumors.
Dr. Tomer Kalisky
Single-cell genomics of kidney development, regeneration, and cancer
The Alexander Kofkin Faculty of Engineering
Tomer Kalisky completed his Ph.D. in physics of complex networks with Prof. Shlomo Havlin from Bar-Ilan University. After a postdoc in systems biology with Prof. Uri Alon at the Weizmann Institute and in bioengineering with Prof. Stephen Quake at Stanford, Tomer established his lab for single-cell genomics in the Faculty of Engineering in Bar-Ilan University.
Annual Activity Report, March 2018 – characterizing cancer stem cells in Wilms’ tumor at the single-cell level
The mission of our lab is to understand how tissues and organs are formed in the human body, how they are maintained and regenerated throughout our lifetime, and what causes them to behave badly and create cancer. Two specific aims are: (i) to find markers for tissue-specific and cancer stem cells for regenerative medicine, targeted therapeutics, and early detection, and (ii) to understand tumor heterogeneity, that is, how tumors differ from patient to patient, in order to design personalized treatment strategies.
To this end, we use single-cell technologies and next-generation sequencing. We dissociate a tissue or tumor into single cells and measure gene expression and sequence information from each individual cell. Then, we use computational algorithms to identify and characterize the different cells types and to understand their roles, fate trajectories, and network of interactions, thereby creating a “Cell Atlas”. Our overall goal is to comprehensively profile embryonic, adult, and diseased tissues at the single-cell level in order to reveal the cellular and molecular mechanism underlying development, regeneration, and disease.
We are mainly focusing on the kidney - a complex organ composed of many cell types that is responsible for removing waste products from the blood, secreting hormones, regulating electrolyte concentrations, and controlling blood pressure. In a recent study that was done in collaboration with Prof. Benny Dekel from the Sheba Medical Center, we compared the single-cell expression profiles of human fetal kidney cells and Wilms’ tumor patient-derived xenografts, and found that not one – but two cell two populations are required for Wilms’ tumor regeneration. We are now performing single-cell RNA sequencing in order to understand the cross-interactions between these two cell populations in order to find a way to distort them.
Dr. Noa Vilchinsky
The Psycho-Cardiology Research Lab
Department of Psychology
Dr. Noa Vilchinsky is the Director of the Psycho-Cardiology Research Lab, Department of Psychology, Bar-Ilan University. Dr. Vilchinsky is a certified rehabilitation psychologist, who has worked for many years with individuals and families coping with cardiac illnesses. She has completed her B.A. IN Tel Aviv University and her Master degree and PhD at Bar-Ilan University. Her main fields of research are psycho-cardiology, dyadic coping with chronic illness, illness-related PTSD, caregiving in challenging health situations, and the importance of being treated with dignity in the medical setting.
Our overall mission in the Psycho-Cardiology lab is to trace the individual and social differences that make the greatest contribution to patients' and caregivers' adjustment.
In the studies we conduct in our lab, we focus on the contribution of dyadic support transactions among cardiac patients and their partners to patients' psychological, behavioral, and physiological outcomes, in longitudinal and prospective studies. A few examples:
We have shown that support provided by the partners has a positive effect on cardiac patients’ psychological (depression); behavioral (smoking cessation, medication taking) and physiological (LDL blood levels) outcomes only insofar as the patients’ own perceptions of the support allow (Vilchinsky et al., 2010; Vilchinsky et al., 2011; George-Levi, Vilchinsky et al., 2016). Thus, we have been able to establish the necessity and importance of applying a dyadic perspective to the investigation of cardiac patients' psychological and physical health. Recently we initiated a prospective, longitudinal dyadic study in which we apply a novel methodology of daily diary assessments. In this way, we hope to be able to trace, on a daily basis, those caregiver support acts that predict changes in patients' health-promoting behaviors.
We are currently focusing on the subject of PTSD among cardiac patients and caregivers. We are currently collecting data with the aim of tracing how partners' support may moderate patients' CDI-PTSD, as well as the association between CDI-PTSD and health-promoting behaviors.
Dr. Ronit Ilouz
Molecular and Cellular Mechanisms of Protein Kinasese in Neurodegenerative diseases
The Azrieli Faculty of Medicine
Dr. Ronit Ilouz was recruited to Bar Ilan University, the School of Medicine as a Senior Lecturer in 2018. She performed her postdoctoral studies at Howard Hughes Medical Institute (HHMI) following a project scientist appointment at the Pharmacology Department, University of California San Diego (UCSD). During the years abroad Dr. Ilouz led and developed the San Diego Center for ScienceAbroad, a non-profit organization that aims to create a dynamic network for Israeli Scientists abroad (currently over 3000 members).
Dr. Ilouz is an expert in the protein kinase field. She provided a significant contribution to the understanding of the molecular structure of Protein Kinase A (PKA). She earned her MSc and PhD in Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine at Tel Aviv University where she focused on Glycogen Synthase Kinase 3 (GSK3) inhibition.
Moving from molecular structure to in vivo morphology and ultrastructure levels of the cell Dr. Ilouz was able to map the subcellular location of PKA regulatory isoforms in mouse brain sections. “ The mosaic maps are akin to a Google map, where one is able to locate a building without losing the context of the city” says Dr.Ilouz. Analysis of multiple regions demonstrates that PKA regulatory subunits are concentrated within discrete brain regions and express unique and consistent patterns of subcellular localization. “This work lay the foundation for analyzing different macromolecular signaling components, that are localized within specific brain regions, in health and disease state” says Dr. Ilouz.
The idea is to translate the genomic data into a three dimensional structure to enable a better understanding of the molecular and cellular mechanisms, and then to control it with a specific and precise drug targeting therapy based on the SNP mutation. Aberrant Protein Kinase A (PKA) localization has been linked to a Parkinson disease. The diagnosed patients have Single Nucleotide Polymorphisms (SNPs) in the PKA_ RIβ gene. The lab is integrating various methods including X-ray crystallography and advanced microscopy techniques as well as molecular biology, biochemistry and signal transduction. Elucidating the cellular and the molecular interactions that are properly controlled by PKA signaling and are dysregulated in the neurodegenerative disease will help discover opportunities and challenges toward personalized medicine.
Prof. Nirit Bauminger-Zviely
Autism Spectrum Disorder (ASD) Research and Intervention Laboratory
School of Education
Prof. Nirit Bauminger-Zviely is a Full Prof at the School of Education. She joined the School of Education in 1997, after graduating with honors from UCLA receiving a PhD in Educational Psychology with specializing on understanding the social – emotional functioning and related intervention of individuals affected by Autism Spectrum Disorders (ASD). During the last three years, Prof. Bauminger-Zviely served as the head of the School of Education in where she has her ASD research and intervention laboratory.
Prof. Bauminger-Zviley's laboratory at the Bar-Ilan University School of Education is at the forefront of basic and applied research on the social-emotional development of children affected by ASD, exploring possible precursors, correlates, and characteristics of peer relations as well as developing innovative manualized evidence-based social interventions, within a holistic model integrating cognitive-behavioral therapy with developmental and ecological orientations. Over the past two decades, Prof. Bauminger-Zviely have examined children’s quality of interactions and relationships using detailed observation scales that were developed in her laboratory specifically for individuals with ASD. Moreover, Prof. Bauminger-Zviely developed paradigms for assessing socio-cognition and socio-communication capabilities, with the aim of examining affective, linguistic, and cognitive correlates of these children’s ability to form social interactions in order to be able to develop tailor-made interventions with regards to the individual differences within ASD.
Prof. Bauminger-Zviley's laboratory may contribute substantially to the Dangoor Center for Personalized Medicine by helping to assess phenotypical characteristics of ASD and other neurobiological disorders as well as by providing guidance and support for the development and evaluation of appropriately personalized interventions, it is also opens-up numerous ways of collaborative efforts to bio-behavioral understanding of the phenotypical characteristics and related interventions for various neurobiological disorders.
Annual report: Tailoring Interventions to ASD Phenotypical Characteristics
Two innovative RCT-social intervention programs were tested recently in Prof. Bauminger-Zviely's ASD laboratory: The S-PSI- a School-Based RCT Peer Social Intervention for Minimally Verbal Children with ASD; and the the PPSI-Preschool Peer Social Intervention to promote Peer Play, Conversation and Interaction for preschoolers with ASD. Both novel evidenced-based intervention models show very promising results in terms of improving the social phenotypical core deficit of individuals with ASD in peer engagement.
Prof. Erez Levanon
The Mina and Everard Goodman Faculty of Life Sciences
RNA editing - Common, Hidden Mutations
Erez Levanon is an associate professor at the faculty of life sciences of Bar-Ilan University in Israel. He received his PhD from Tel-Aviv University after graduating the Adi Lautman Interdisciplinary Program for Outstanding Students and was a postdoctoral research follow at the genetics department of Harvard Medical School. Prior to that, he was a senior scientist in Compugen LTD. He has published over 70 manuscripts and won several awards and fellowships including the Clore, Fulbright, Rothschild, Alon and Krill.
It is widely accepted that, with the possible exception of rare and random somatic mutations, a genome remains unaltered throughout an organism’s life and serves as a template for exact RNA copies. However, endogenous and powerful means of creating inner genomic diversity is now known to exist: RNA editing, where ADAR proteins alter A-to-I leading to genomically encoded adenosines (A) to be read as guanosines (G). Its magnitude is unprecedented, with millions of RNA editing sites already identified in human. However, difficulties in detecting and measuring such events reliably, mean that the implications of this massive rewriting have hardly been studied at all.
Just as RNA editing events might drive adaptation in a way similar to genomic mutations, deregulated RNA editing might have an effect similar to that of disease-related genomic mutations. Altered editing could manifest as: changes in the level of recoding at known sites; creation of novel disease-specific recoding events; creation of novel editing-assisted splicing events; or modified editing patterns of circRNAs, miRNAs and their targets. These aberrant editing events could be viewed as a new class of non-heritable ‘RNA mutation’, which is not detectable by DNA sequencing. In our lab we developed a unique computational approach to detect RNA editing events and apply it across many biological conditions. As is the case with somatic genomic mutations, most newly introduced RNA mutations are likely to be passenger mutations, but a few may serve as driver mutations and represent novel candidates for therapeutic and diagnostic purposes. In our lab we found cases of altered editing in various cancer types, neurodegenerative and autoimmune diseases. Moreover, we have shown that that response for treatment, in several of the diseases, can be predicated from the editing landscape.
Dr. Gur Yaari
Computational Systems Immunology Laboratory
The Alexander Kofkin Faculty of Engineering
Dr. Gur Yaari joined the BIU Department of Bio-Engineering as a Senior Lecturer in 2013, after a post-doctoral fellowship at Yale University. His Research at BIU focuses on adaptive immunity, from a systems perspective.
Behind the phenomenal success of the immune system in fighting countless threats lies its ability to diversify, adapt and form long term memory. Specificity of the adaptive immune system is achieved by the dynamics of lymphocytes repertoires: T and B cells that following exposure to a threat undergo clonal expansion and selection. B cells in particular go through cycles of somatic hypermutation and affinity driven selection, generating a repertoire of highly specific dedicated antibodies. Thus, the antibody repertoire stores information about specific threats that each individual has encountered, making it a potent candidate to revolutionize the field of personalized medicine.
Dr. Yaari and his team combine experimental and computational expertise to mine biological knowledge from these diverse immune repertoires. They use high throughout sequencing of the variable region of the antibodies, along with dedicated computational algorithms for this task.
Annual Activity Report, March 2017
To date we applied antibody repertoire analysis to a wide range of diseases ranging from cancer to autoimmune diseases. Examples include colon and liver cancer, influenza, multiple sclerosis, celiac, and Hepatitis C virus (HCV) infection. In one study for example, we compared B cell responses between HCV spontaneous clearers and chronic patients, and were able to design broadly neutralizing antibodies based on the sequenced repertoires, as well as to identify an immune signature that differentiates between these responses. This signature can be used to fit a treatment to each patient based on their repertoires. In another ongoing study, we characterize the naïve antibody repertoire of celiac patients, to discover signatures that might enable prediction of the risk for this autoimmune disease in healthy individuals, including disease severity and personalized treatments.
Prof. Aron Weller
Developmental Psychobiology Laboratory
Department of Psychology
Aron Weller received a PhD in Psychology from the Johns Hopkins University, Baltimore, MD, USA. His postdoctoral training was at the Psychiatry Dept., Cornell University Medical College, and (during a sabbatical year) at the Psychiatry Dept., Columbia University College of Physicians and Surgeons.
Since October 1989, he is at the Psychology Department, Bar Ilan University, starting as Lecturer and from 2001 onward as Professor. He co-established undergraduate and graduate interdisciplinary programs in the Brain Sciences at Bar Ilan, and served as head of this program and as head of the University’s Interdisciplinary Studies Unit. His lab is in the Gonda Brain Research Center.
His research team’s theme is epigenetic: searching for neurochemical mechanisms at sensitive developmental periods that may "program" and underlie the risk for unhealthy development.
Current research examines, separately: a) emotion regulation, using animal models of depression and anxiety, and b) intake and body-weight regulation, using animal models of binge eating, overeating, dieting and obesity in individuals. Recent focus: Epigenetic mechanisms of trans-generational obesity and “resistance” versus “susceptibility” to obesity and to binge eating.
Annual Activity Report, March 2018
In collaboration with Dr. Noam Meiri of the Vulcani Institute we have found a number of epigenetic mechanisms/markers that are candidates for underlying overeating and obesity. We have been using a rat model of high-fat-diet (HFD)-induced obesity. Specifically, we found DNA hypermethylation and post-translational histone modifications and the cross talk between them, on regulatory segments of the genes for Pro-opiomelanocortin (POMC) and the melanocortin 4 receptor to be associated with overweight and dieting. Furthermore, we have found that epigenetic markers on the POMC promotor can be transferred from parents to their offspring.
Currently we are searching for epigenetic mechanisms/ markers underlying resistance vs. susceptibility to diet-restriction-induced weight loss in individuals. In order to explain epigenetic heritability we are studying the possible transfer of the epigenetic markers through germ cells.
These studies have the potential to produce biological markers for susceptibility/resistance to disease, and for individual potential to respond to treatment, which can then be examined for relevance as biomarkers in rat, then in human, blood tests. These markers are tied closely to underlying neurobiological mechanisms, directing the efforts for individual-tailored treatment.
Prof. Sol Efroni
The Systems Biomedicine Laboratory
The Mina and Everard Goodman Faculty of Life Sciences
Prof. Sol Efroni is a former research fellow at the National Institutes of Health (Bethesda, MD). He joined the Mina & Everard Goodman Faculty of Life Sciences as a Senior Lecturer in 2009. Since then, the Efroni Systems Biomedicine Lab focuses on the genomics of tumors and the genomics of the immune system, using high-throughput methods, network biology and machine learning.
Since T cells and B cells have the unique ability to change their own genome to get better at what they do, T cells are often different from one another in their ability to “see”. Their combined perspective makes up the Immunological Repertoire, which is fundamentally different between individuals. Recent progress in the ability to sequence genomes, and progress with computational tools, now allows us to observe the T-cell repertoire in different patients. We build on these tools to associate diseases, their treatments, and their detection, with the T cell repertoire.
Building on the recent, and ever-growing, flood in genomics data, we in the Systems Biomedicine lab also develop tools to use pathway and network knowledge to discover hidden properties of cell regulation out of high-throughput data. We have been using pathway knowledge on top of gene and protein information to perform diagnosis and prognosis of samples from cancer patients and have shown the advantage in using such approach in multiple papers (all of them appear in the “Publications” section in this website). Often, we are able to highlight the pathways most critical to make diagnosis (or prognosis). We follow up on these findings in wet-lab experimentation to learn more about the mechanisms of these critical pathways.
Prof. Efroni received his B.Sc. in Physics from Tel-Aviv University, his M.A. in Cognitive Sciences from The Hebrew University and his Ph.D. in Immunology and in Computer Science from The Weizmann Institute.
Dr. Dana Atzil-Slonim
Clinical Research meets Analytic and Feedback Technologies (CRAFT)
Department of Psychology
Dana Atzil-Slonim received her PhD from the Hebrew University and joined Bar-Ilan University at 2015. She is currently the head of the clinical track at BIU's Psychology Department. Dana has a lengthy practical experience as a clinician and supervisor in clinical psychology. Her main research goal is to shed more light on the process and mechanisms of change that underlie gains in psychotherapy. This has important implications for improving the effectiveness of treatments to those suffering from emotional pain as well as for developing training and supervision strategies that foster successful psychotherapy interventions. The research conducted in her lab aims to advance the ideal of greater integration between research and practice in the field of clinical psychology in which information flows reciprocally between researchers and clinicians. To do so, she and a team of researchers from the Psychology Department at Bar-Ilan University implement a model in which all clinical activities within the research clinic are available for scientific inquiry. This includes a clinical research protocol enabling session-by-session monitoring, within-session recording, and therapist feedback for more than 150 treatments each year.
The importance of tailoring therapeutic interventions to the specific needs and characteristics of the individual patient has long been recognized by clinicians. However, traditional approaches to clinical diagnostics and psychotherapy have not been contributing to such personalization. Contrary to traditional nomothetic methods, idiographic assessment and modeling of intraindividual dynamic processes, as well as the use of machine learning techniques to analyze massive amount of multi-modal data, hold tremendous promise for tailoring psychodiagnosis and psychotherapy to the individual patient who suffers from mental health disorder. In a current collaboration between psychology experts and leading computer scientists, Dana and her colleagues are conducting a multidisciplinary project that integrate moment-by-moment linguistic, vocal, facial, kinesthetic, and physiological data, with the aim of developing person-specific assessments of treatment response and predictions of relapse or recovery in clients who suffer from mental health disorders and especially from depression. This approach is expected to yield unique insights regarding the processes that underlie psychopathology and therapy gains.
Dr. Itay Onn
Chromosome Instability and Dynamics Laboratory
The Azrieli Faculty of Medicine
Dr. Onn is a former Research Associate at the Department of Embryology, Carnegie Institute for Science, Baltimore, USA. He joined BIU's Azrieli Faculty of Medicine in 2014, being one of the founder researchers. In his lab at BIU he studies mechanisms that control the spatial organization of the chromatin in the nucleus of eukaryotic cells.
The DNA in eukaryotic cells is packed by proteins into chromatin fibers. Structural Maintenance of Chromosome (SMC) is a family of protein complexes that mediate long range interactions between remote chromatin regions on the same molecule and between separate chromatin fibers. The organization of the chromatin by SMCs plays a central role in the structural stability of the chromatin, they are essential for accurate segregation of the genetic material when cells divide and they controls the timely expression of genes in respond to cellular and environmental cues.
In recent years the impact of SMCs on human health has been recognized. Mutations in genes encoding for SMCs are associated with genetic disorders of intellectual disability and cancer. “Our knowledge of the mechanism by which SMCs cause human disorders in poor” says Dr. Onn. “If we’ll dissect SMCs mechanism of action we will be able to understand their pathogeny and develop means to control their activity. SMCs are new and exciting targets for personal medicine”.
Dr. Onn and his team at BIU are using a multidisciplinary approach to decipher the molecular basis of SMCs activity and to develop new small molecules to manipulate their activities. “Our long term goal is to improve diagnosis in patients carrying mutations in SMCs encoding genes. Furthermore, we aim to harness SMCs to personal medicine in order to develop new therapeutic strategies and improve human health”.
Prof. Mira Barda-Saad
The Mina and Everard Goodman Faculty of Life Sciences
Mira Barda-Saad obtained her PhD degree in Molecular Immunology summa cum laude in 1999, following a collaborative research at Bar-Ilan University (BIU) and the Weizmann Institute of Science (WIS). She performed her initial postdoctoral studies at the WIS (1999-2001) and later at the NCI/NIH, Bethesda, MD, USA (2001-2006). She received the Fellows Award for Research Excellence (FARE) from the NIH (2005) for identifying the dynamics and molecular linkage between T-cell antigen receptor (TCR) signaling to the actin machinery, and specifically to the Wiskott-Aldrich Syndrome protein (WASp). In October 2006, she joined the Faculty of Life Sciences at BIU. She was awarded the Taubenblatt Award for Research Excellence in Biomedicine in 2009. Since November 2016, Prof. Barda-Saad serves as president of the Israeli Immunological Society (IIS). Mira Barda-Saad’s research focuses on signal transduction mechanisms in immune cells, and specifically, on cytoskeletal networks regulating leukocyte behavior in health and disease e.g. cancer and primary immunodeficiencies.
Annual Activity Report, March 2017 – Novel Personalized Immunotherapeutic Approaches For Treating Cancer. Immunotherapy aims to strengthen the body’s immune system in order to treat pathologies e.g. cancer. In order to escape the immune system, cancer cells often disturb the balance between activating and inhibitory signals within lymphocytes that play a key role in the elimination of cancer cells. A major escape mechanism of tumors involves the downregulation of activating ligands, which prevents recognition by the immune cells, or upregulation of inhibitory ligands that suppress the immune response. As such, a major immunotherapy that evolved in the recent years, known as the immune checkpoint blockade, aims at masking inhibitory receptors e.g. PD-1, CTLA4 etc. expressed over the surface of immune cells or their ligands expressed by cancer cells. This immunotherapy has resulted in remarkable immune-mediated clearance of incurable tumors and metastases. However, many patients do not respond to treatment with the currently available inhibitors due to genetic incompatibility of the patient's immune system or of the tumor cells, or otherwise demonstrated severe autoimmune reaction, resulting in life-threatening complications or even death. These data emphasize the need for the development of novel protocols for designing genetically compatible, tailor-made i.e. personalized treatments to regulate the immune response in a robust and safe manner. Prof. Mira Barda-Saad's (MBS) laboratory focuses on the inhibitory signals. The group recently identified novel, intracellular immune checkpoints and harnesses them in order to boost the immune response (Science Signaling, 2016 and EMBO J., 2018). Several limitations exist concerning this methodology as an efficient and safe therapeutic approach for the majority of cancer patients. By using personalized medicine approach, the many variables encompassed in the different layers of regulation of the immune system can be mapped to enable designing the appropriate treatment for a specific patient. Screening a given patient’s profile from the perspective of immune cell polymorphisms and heterogeneous tumor microenvironments, can give critical insights into which treatments may exhibit the best therapeutic potential, yet not induce autoimmune pathologies.
Dr. Achia Urbach
Stem Cells and development Laboratory
The Mina and Everard Goodman Faculty of Life Sciences
Dr. Achia Urbach joined the Faculty of Life Sciences at the Bar Ilan University in 2014. During his PhD studies at the Hebrew University, Jerusalem, Achia was one of the pioneers to model human genetic disorders by human embryonic stem cells (hESCs). Then, during his post-doc in Boston Children’s Hospital and Harvard Stem Cell Institute, he compared between hESCs and induced pluripotent stem cells (iPSCs) based models. In addition, he studied the effect of the pluripotency marker Lin28 on the kidneys. Using transgenic mice that enable conditional Lin28 over-expression he showed that Lin28 over-expression during kidney embryogenesis sustains the proliferation of the renal progenitor cells (which normally exist only until the first few postnatal days). He further showed that the abnormal proliferation of these progenitor cells leads to the formation of a tumor similar to human Wilms tumor, which is the most common pediatric renal cancer.
The overall goal of Achia’s Lab in BIU is to combine in-vivo mouse models, ex-vivo organoid models and in-vitro hPSC based models in order to advance our understanding regarding the development of the kidneys and the lungs and regarding kidney and lung disorders.
Specifically, the current two major interests in the lab are:
- To study the effect of Lin28 over-expression on developmental and cellular processessuch as embryonic lung development, cystic kidney formation and primary cilia biogenesis.
- To model renal disorders by hPSCs both by using hiPSCs derived from patients’ somatic cells and by mutated hESCs (derived from PGD embryos or by genetic manipulations).
Prof. Dror Fixler
Nano photonics, Fluorescence Imaging and Microscopy Research for Personalized Medicine
The Alexander Kofkin Faculty of Engineering
Prof. Dror Fixler is the Director of the Institute of Nanotechnology and Advanced Materials (BINA), and a Lecturer at the Faculty of Engineering.
Fixler is a BIU-educated expert in electro-optics and photonics research including the emission, transmission, detection and sensing of light for biomedical properties. His primary foci are developing new technologies for super resolution microscopy, medical testing, and communications networks.
Fixler's research deals with theoretical and practical models for reconstructing the optical properties of participating media by nano photonic tools. His theory is based on a robust generalization of the diffusion theory; Gerchberg-Saxton algorithm; dipole-dipole approximation and other methods. On the practical side he uses lasers, LEDs and microscopes.
Human tissue is one of the most complex optical mediums since it is nonhomogeneous. Its optical properties are unknown and vary in different tissue areas and physiological states. Because of all of the above, in vivo imaging is a difficult task. In Dror Fixler’s lab we deal with this difficulty by focusing on detection rather than imaging. We use methods which probe the tissue properties by means of the diffusion reflection profile, adding nano particles as contrast agent, the full scattering profile and its isobaric point or iterative phase multiple measurement reconstruction techniques. Furthermore, we use changes in optical parameters, such as fluorescence life time and fluorescence anisotropy to probe the biological surroundings. In Dror’s lab we are able to fabricate Gold nano particles (spheres and rods), organic nano particles (Vitamin B12, Penicillin and Methylene Blue) as well as tissue like phantoms. The applications for these methods include diagnosis of diseases such as cancer and atherosclerosis, examination of different physiological parameters, visualizing enzyme activity and early stage cell mutation detection.
Prof. Ron Unger
Computational Biology, Data Mining and Personalized Medicine
The Mina and Everard Goodman Faculty of Life-Sciences
Ron Unger is a professor in the Mina & Everard Goodman Faculty of Life Sciences in Bar-Ilan University, Israel. He earned his Ph.D. at the department of Computer Science in the Weizmann Institute of Science in 1990, and spent a post-doctoral period at the University of Maryland. His research interests are in the interface between computer science and biology, using bioinformatics and computational biology techniques. Many of his works are in the field of Personalized Medicine. Prof. Unger is the founder and the head of the Computational Biology program in Bar-Ilan University, as well as the founder and head of the unique program “Genomics and Biomedical Informatics for Physicians”. Prof. Unger was the president of the Israel Society of Bioinformatics and Computational Biology (ISBCB). His publication list contains more than 85 scientific papers and two textbooks on computational biology and bioinformatics.
Among our current main research projects are: Computational studies of protein folding where we examine the role of chaperones in the folding process and analysis of non-coding RNA molecules in parasites and RNA editing.
In the field of personalized medicine, we study the clinical implications of individual genomic variations in condition such as high blood pressure, Crohn or type2 diabetes. We also run several studies in medical data mining including analysis of data of patients that undergo bone marrow transplantation to predict their survival rates, analysis of medical records to predict onset of T2D, and analysis of risk factors for cesarean section deliveries.
Dr. Nir Qvit
The Azrieli Faculty of Medicine
Protein-Protein Interactions in the Field of Personalized Medicine;
A Precision Medicine Approach for Mitochondrial Dysfunction
Dr. Nir Qvit completed his doctorate in organic chemistry, at the Hebrew University in 2008. His work focused on developing different strategies for synthesis of small molecules, and peptides for various therapeutic applications. Later that year he joined the department of Chemical and Systems Biology, at the Stanford School of Medicine as a postdoctoral fellow. During his postdoctoral training Dr. Qvit gained expertise in a variety of biochemical and cell-based assays, as well as various animal disease models. In 2012 Dr. Qvit received the SPARK Grant, a transitional research grant that facilitates translating academic discoveries into drugs that address unmet medical needs. He also received the prestigious Kaye Innovation Award for demonstrating extraordinary creativity as a medicinal chemist, the Burroughs Wellcome Fund Collaborative Research Grant and the European Molecular Biology Organization (EMBO) Fellowship. He holds an M.B.A. and has been fortunate to have several collaborations with industry. In 2017 he joined Bar-Ilan University’s (BIU) Azrieli School of Medicine as a Senior Lecturer. At BIU his research focuses on development of novel tools to regulate protein-protein interactions (PPIs) in a highly specific manner.
PPIs are central to most biological processes and are often dysregulated in many diseases. Targeting PPI-sites offers the potential of differentiating between many proteins and even homologues, since the sequence and/or structure of these PPI-sites are usually unique. Targeting PPIs offers the potential of differentiating between many and even similar proteins, therefore increasing the specificity and lowering the toxicity. Mitochondria are vital organelles that regulate cellular energy and cell death, and their correct function is also dependent on PPIs. They possess several vital mechanisms that regulate their homeostasis, including fusion and fission (division). The Qvit lab work on developing regulators that mediate the interaction between proteins involved in mitochondrial regulation and mitochondrial proteins, for therapeutic purposes.
Prof. Gal Yadid
A proactive and personalized platform for treating psychiatric diseases
The Mina and Everard Goodman Faculty of Life Sciences
Professor Gal Yadid received his DSc in Neuropharmacology, Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel and was honored to be among the direct post-doctorate student of the luminary and role model Irve Kopin at the Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke. Since 1994 he is the Head of the Laboratory of Neuropsychopharmacology at the Mina & Everard Goodman Faculty of Life Sciences and the Gonda Brain Research Center of Bar-Ilan University.
His research group focuses on developing pharmacological and non-pharmacological treatment modalities for psychiatric diseases – specifically drug addiction, depression, and post-traumatic stress disorder (PTSD)– using behavioral models in combination with neurochemical, molecular, and computational methods, as well as nanotechnology, in a bi-directional approach. Over the last eight years, Prof. Yadid has recruited personnel with expertise in state-of-the-art epigenetic techniques, and thus established ongoing collaborations with leading scientists in the field. Several major findings credited to the Yadid lab have been translated into practice in clinics. One main, recent project is the following:
Epigenetic and genetic landscapes for discovering novel therapeutic targets for the treatment of drug abuse, PTSD, and depression. Prof. Yadid has shown that unbiased, broad epigenetic screening points to important networks of genes involved in effective ways to develop new therapeutics for the treatment of psychiatric diseases. First, he demonstrated the role of accumbal DNA methylation and downstream targets of DNA demethylation in the incubation of cocaine craving. He also found that the targeting of specific proteins whose genes were demethylated by a DNA methyltransferase inhibitor, decreases cue-induced cocaine seeking. These findings have important implications for understanding drug-related behavior, and suggest possible future therapeutic targets for dealing with drug abuse.
Prof. Yadid also uses a high construct validity PTSD animal model in combination with capture sequencing and pyrosequencing to delineate DNA methylation 'predictors' of individual PTSD behavior in peripheral blood mononuclear cells from live rats prior to exposure to trauma, immediately after exposure to trauma, and at the termination of the experiment, thus defining their evolution during PTSD progression. He recently discovered that PTSD susceptibility and resilience are associated with distinct and broad DNA methylation changes. Whole-genome screening and molecular analysis also suggested a combination of two approved natural products as an effective, novel ‘cocktail’ that could be adapted for use in treating PTSD patients.
Yadid’s scope suggests a shift in mental health care from a reactive to a proactive and personalized discipline. An interactive and dynamic biological-psychological approach (including neurochemical, epigenetic, microbiome, and cognitive-behavioral parameters) may lead to a significant personalized rehabilitation.
Prof. Arnon Blum
Vascular Medicine and Endothelial Stem Cell Regulation
Prof. Arnon Blum received his MD at the Technion, specialized in Internal Medicine at Hebrew University, and then in Cardiology at Tel-Aviv University. He served in the IDF as a Flight Surgeon (Lieutenant Colonel). Since 1999 Prof. Arnon Blum has been the Director of the Internal Medicine Ward at Baruch Padeh Medical Center-Poriya, Tiberias. Prof. Blum research focused on Vascular Biology and Vascular Stem Cell research, receiving his training at the National Institutes of Health (Bethesda, MD, USA; 1997-1999 and 2006-2008) exploring means for cardio-vascular regeneration. In 2011-2012, he was invited as a visiting Professor to lead a clinical trial at the University of Miami for adult (mesenchymal) stem cell transplants to patients with severe heart failure. There, he discovered a key mechanism that explains the beneficial effects of cell transplantation to the failing heart. Prof. Blum has published more than 170 papers in peer-reviewed journals and chapters in Cardiology Textbooks - the most recent one addressing techniques for stem cell transplantation to the heart (Grossman 8th edition, 2014). He serves on the editorial board of 25 journals in Cardiology, Internal Medicine and Translational Medicine, and is the Editor in Chief of one of these. Prof. Blum was head of the department of medicine in Azrieli Faculty of Medicine, and is a member of 5 steering committees at Bar-Ilan University's. Prof. Blum serves now as Head of the Academic and Scientific Affairs of the Baruch Padeh Medical Center.
Personalized cardiovascular medicine: Prof. Blum was part of a team that developed a personalized approach to diagnose and treat patients with cardiovascular disease.
- Advanced ultrasound (US) imaging. Over the past 25 years, Prof. Blum has developed advanced techniques for predicting a patient's potential for serious cardiovascular events (heart attack). Using non-invasive ultrasound imaging can measure endothelial function, estimate individual's cardiovascular risk. It is considered one of the most advanced techniques of personalized medicine in cardiology.
- Endothelial Stem Cells. The development of atherosclerosis is dependent on endothelial stem cells (EPCs) activity. Endothelial stem cells are responsible for the maintenance of the endothelium. Prof. Blum has discovered a stem cells' bioassay that can characterize patient's ability to regenerate damaged blood vessels.
The advanced vascular imaging technique and the ability of a subject to build its own stem cells are considered "personalized medicine", both serve as an imprint, they can be improved following intervention, and are used as a follow up objective method to measure the success of interventions of individual subjects.
Prof. Rachela Popovtzer
Nanotheranostics for Personalized Medicine
The Alexander Kofkin Faculty of Engineering
Rachela Popovtzer is an Associate Professor, head of the Bioengineering track and head of the Nanomedicine lab in the Faculty of Engineering at Bar Ilan University, which she joined in 2008. She is also a member of the Bar-Ilan Institute of Nanotechnology and Advanced Materials (BINA).
The Popovtzer lab strives to develop innovative nanotechnology-based solutions for broad applications, including early diagnosis of disease, targeted drug delivery with reduced side effects, and novel therapeutic approaches. The lab's vision is to have a major impact on the future of medicine. The lab has a multidisciplinary research approach, integrating researchers from the fields of engineering, chemistry, biology and medicine.
Novel nanotechnology-based solutions are crucial for early diagnosis of disease, targeted drug delivery with reduced side effects, and novel therapeutic approaches. Nanoparticles that combine diagnostic and therapeutic ('theranostic') applications have great potential to enhance personalized medicine for currently incurable diseases, such as cancer and brain disorders. Our ongoing research aims to develop intelligent nanotechnologies that are optimally sensitive, targeted to the individual tumor composition or pathological region, and allow early stratification of responders and non-responders. Our technique also enables longitudinal tracking of therapeutic stem cells and exosomes in deep tissue. We use non-invasive CT to image nanoparticles over time, expanding the role of this imaging modality beyond its present structural imaging capability, and endowing it with functional and molecular-based capabilities. These nanotechnologies can serve as powerful tools with personalized therapeutic abilities, and high predictive value of immunotherapy and cell therapy success.
Prof. Yanay Ofran
Studying the effects of genomic variations on protein function and interactions
The Mina and Everard Goodman Faculty of Life-Sciences
Yanay Ofran completed his PhD (with distinction) at Columbia University, NY, where he worked at the dept. of Biomedical Informatics and at the dept of Molecular Biophysics and Biochemistry. At Bar Ilan University, Prof. Ofran heads the lab of functional genomics and systems biology and teaches at the program for Genomics and computational medicine for physicians, the only program in Israel that trains physicians in medical informatics in genomics.
Ofran lab studies molecular interaction in health and disease. The research project in the include:
Developing methods for predicting phenotypes from genome
The vast majority of genomic variations that are found in the genome of any person are not known to be associated with any of that person’s phenotypes. Many of them are variations that have rarely, or even never, been observed in other people and hence cannot be associated statistically with a phenotype. Others may have been observed before but have not been associated with a phenotype. The variation-phenotype associations that have been identified are typically weak and do not allow for sensitive and specific prediction of phenotypes. In a series of studies Ofran lab uses data from GWAS, biological networks and pathway analysis to map phenotypes to pathways and devise new methods for predicting phenotypes from newly sequenced genomes.
Studying antibody-antigen interaction in health and disease
The immune system is involved plays a role in almost all diseased. At the heart of the immune system is a mechanism for molecular recognition – the specific binding of antigens by antibodies. Ofran lab is studying the mechanisms that allow antibodies to recognize antigens. By predicting what a given antibody binds, and analyzing the antibody repertoire of specifc patients Ofran lab is searching for antibody based biomarkers. Using computational tools for antibody design the lab is also collaborating with pharma and biotech companies to design and engineer new antibody-based tehrapies.
Using computational and molecular methods to study drug-protein interactions
Drugs are molecules that bind to proteins and affect their function. Another focus on the research of Ofran lab is to charaterize the interfaces between proteins and drugs and to develop tools to predict whether and how a given drug will interact with a given protein. These tools can help screening of drug candidates that are custom-tailored to the vartions in sequence of sepecific people.