The Team

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.

OUR RESEARCHERS

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:

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.

Professor Karl Skorecki is the current Dean of Azrieli Faculty of Medicine, the Bar-Ilan University’s School of Medicine in the Galilee, in Safed.

A specialist in internal medicine and kidney disease, Prof. Skorecki has many years of experience as a clinician, medical educator and research scientist. He is gold-medal MD graduate of the University of Toronto, who then pursued clinical and research training in internal medicine, nephrology and advanced research training in cell and molecular biology, at Harvard Medical School. After his postgraduate studies in Boston, followed by Faculty positions at the University of Toronto and affiliated medical centers, Prof. Skorecki and his family made Aliyah in 1995.

Karl has held several academic and medical leadership positions in Medicine, Nephrology, Genetics and Biomedical research at Rambam Medical Center and the Technion. From 1995 to 2005, he served as Director of Nephrology, at Rambam Health Care Campus in Haifa, and Professor and Director of and Molecular Medicine at the Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology. Between the years 2000-2015 Prof. Skorecki served as Director of the Rappaport Research Institute at the Technion, and from 2005 served as Director of Medical and Research Development, at Rambam Health Care Campus, Haifa.

Prof. Skorecki’s major research interests are in the genetics of kidney disease, and the genetic history of Jewish and Near East communities. His activity in population genetics began with a series of research studies, tracing founding patrilineal and matrilineal lineages in Near East and Jewish populations, and has extended to genome-wide studies including many global populations. Combining population genetics and evolutionary medicine, Prof. Skorecki and his team identified high allele frequency variants at a genetic locus, termed APOL1 which accounts for fully 70% of the 5-fold increased burden of progressive kidney disease in Sub-Saharan African ancestry and African diaspora populations, with 80 million people worldwide at genetic risk.

The prolific research activity of Prof. Skorecki has led to more than 250 papers, book chapters and a number of patents.

Prof. Skorecki has been awarded prestigious prizes, including William Goldie Prize, Dept. of Medicine, University of Toronto, Elkeles Prize for Excellence in Scientific Research, Jewish National Fund, the Undergraduate Teaching Excellence Award, Rappaport Faculty of Medicine - every consecutive year from 1996 – to 2018.

Prof. Skorecki has won prestigious grants from NIH, ISF, BSF, and others, and has trained scores of MSc and MD students.

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. Hava Gil-Henn Website >>

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. Evan Elliot Website >>

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. Meiytal Gal-Tanami Website >>

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. Omry Koren Website >>

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.

The Mina and Everard Goodman Faculty of Life-Sciences

Tumor Immunotherapy

(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.

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.

Abstract

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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 8^th 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.

Innovative Solution for Reducing Health Inequities: Attaining the Potential of Precision Medicine

Dr. Sivan Spitzer-Shohat, an organizational sociologist, is the principal investigator of ‘HEAL’ – Health Equity Advancement Lab and Head of Population Health Education at the Azrieli Faculty of Medicine, BIU.

Dr. Spitzer-Shohat received her masters in theoretical sociology and her doctoral degree in the interdisciplinary track, both from the University of Haifa, Israel. She completed her post-doctoral training at the Center for Health and the Social Sciences, University of Chicago as well as two prestigious fellowships at the National Institute of Health.

Dr. Spitzer-Shohat’s interests lie in the study of health inequities, and more specifically, in identifying, designing, and evaluating organizational strategies aimed at reducing health care inequities through the prism of organizational change and implementation science. The aim of personalized medicine conveys the definition of equity, aiming to provide care to each person’s needs. Yet it is not enough to focus on the disease (bio-markers) or social circumstances (social-markers). An important player in health inequities research is the organization. Current research is lacking in terms of understanding the facilitators and barriers to implementation of organization-wide equity initiatives and how organizational mechanisms may help reduce inequities in care.

Using implementation science and organizational change frameworks and theories, research projects carried out in HEAL by Dr. Spitzer-Shohat and her team focus on translating equity from value to action through complex organization-wide change efforts in both community and hospital settings in a wide range of health and healthcare topics including chronic disease management and integration of care.

Spitzer-Shohat leads the ETGAR program in which students assist vulnerable patients following discharge in their transition from hospital back home. ETGAR has been chosen by Bar-Ilan University as its Flagship project five years in a row receiving funding from the competitive Vatat-Malag program. Spitzer-Shohat also led the Azrieli Faculty of Medicine’s COVID-19 bio-psycho-social health response platform in which over 80 students either assisted primary care clinic teams across the Galilee to address the knock-on-effects of COVID-19 on the care of chronic patients or assisted Arab municipalities to raise awareness to COVID-19 preventive behavior among elderly residents.

Computational Immunology and Network machine learning

Prof. Yoram Louzoun has studied mathematics and physics at Hebrew University, then continued to brain research in his Ph.D. and from there to immunology in his post doc in Princeton. He now heads a laboratory composed of mathematicians, Life scientists, Computer scientists and physicists involved in multiple domains of computational biology, machine learning, stochastic processes and graph theory.

Research domains.

Network dynamics. We investigate the evolution of networks over time and the mechanisms generating this evolution. The methods developed are applied to neural networks as well as networks in all domains of biology and human sciences. In recent years, we have contributed multiple models and measures allowing the extraction of network content from the observed structure. This includes for example: hierarchy in network, transfer of information, and even the biological function of a neuron or a protein, based on the structure of the network surrounding it. This has led to a new approach in Machine Learning, where the properties of each nodes are learned from the structural aspects of a network surrounding each node. These methods combine novel graph theory methods with advanced deep learning.
We collaborate with Ezer Miztion, the National Marrow Donor Program in the US, as well as parallel organizations in Europe to study all aspects of bone-marrow transplants and their relation to the host HLA, including among others, the analysis of the MHC binding peptide in the host and in pathogens, the distribution of HLA alleles and haplotypes in the population and the dynamics producing those, the development of optimal matching algorithms. This translational research is done in close collaboration with the organization directly in charge of bone marrow transplants in Israel and in the world.
Repertoire analysis. We study the development of the B and T cell receptor repertoire. This analysis is performed both from the theoretical point of view and from a data analysis standpoint. We study the selection mechanisms affecting the B cell receptor, including a strong selection on the D segment D gene that is not induced by stimulation by antigens, but is rather at the rearrangement level, a bias for VJ pairing in H and L chain, and the properties of TCR selection in the bone marrow and periphery. We are currently developing methods to predict history of infections using a combination of machine learning and sequence analysis.
Microbiome analysis. We study in collaboration with Omry Koren from the medical school the properties of microbiome in different hosts, and develop methods to estimate future development of medical conditions based on current microbiome. Our main interest is in microbiome time-series analysis and the possibility to predict future development of microbiome and related conditions.

The research performed in the group of Yaron Shav-Tal is focused on dissecting the kinetics of the gene expression pathway in single living cells using fluorescence live-cell microscopy and tagging of DNA and mRNA molecules. Yaron Shav-Tal received his MSc and PhD degrees from the Weizmann Institute of Science. During the years 2002 to 2005 he was a post-doc at Albert Einstein College of Medicine in New York. In the laboratory of Robert Singer he unraveled the dynamics of mRNA travels in the nucleus. Since 2005 he is at the Mina & Goodman Faculty of Life Sciences and the Institute of Nanotechnology at Bar-Ilan University in Israel. He is a Full Professor and Vice Dean at the Faculty of Life Sciences.

The studies in Shav-Tal group have specifically focused on fundamental regulatory points in the gene expression pathway and have been motivated to the study of the mRNA molecule. Fundamental questions that have been explored relate to the unraveling of the coupling and interplay between transcription and co-transcriptional mRNA processing events, quantifying the dynamic pathway of the mRNA in the nucleoplasm and export through the nuclear pore on the single-molecule level, and examining the fate of mRNAs when they reach the cytoplasm and localize to cytoplasmic granules.

The Shav-Tal group has been interested in the coupling between the different processes of gene expression and how they regulate and affect each other; for instance, how does the nucleoplasmic phase of an mRNA affect its cytoplasmic fate. To this end they have focused on visualizing and analyzing the kinetic aspects of the gene expression pathway. In addition to the specific biological questions, they have expanded technical capabilities by devising new approaches for studying genes at the utmost endogenous level possible (single-gene level), as well as performing single-molecule analysis.

Live-cell measurements are performed on fluorescence microscopes and include quantifications of the measured processes using single-molecule analysis and mathematical modeling. While many of the studies have specifically focused on fundamental regulatory points in the gene expression pathway, collaborations with other groups have led to new directions such as examining the fate of mRNAs and their binding proteins in virus infected cells in collaboration with Prof. Ronit Sarid, and the testing of new types of fluorescent probes that bind RNAs, in collaboration with Prof. Bilha Fischer (Chemistry Department) in order to devise new strategies for detecting RNAs in cells, tissues and biopsies from patients.

Prof. Ramit Mehr – brief biography and research summary

Prof. Ramit Mehr heads the computational immunology lab in Bar-Ilan University since 1999, and was among the first to apply systems biology tools to study lymphocyte development and repertoire diversification. She has served in the boards of the Society for Mathematical Biology (SMB), the Society of Industrial and Applied Mathematics (SIAM)'s special interest group in Life Sciences (SIAG-LS), the Israeli Society for Theoretical and Mathematical Biology, the Israeli Immunology Society, and the Israeli Society for Bioinformatics and Computational Biology. She has recently been Elected as a Fellow of the Society for Mathematical Biology (SMB); The SMB’s Fellows Program honors members of the Society who are recognized by the scientific and scholarly community as distinguished for their contributions to the discipline.

The Mehr group performs research in computational and mathematical immunology. We use mathematical models, computer simulations and bioinformatical analyses, in order to understand the dynamics of lymphocyte repertoires – those of B and T cell receptors (BCRs and TCRs). The work performed in the Mehr group has led to several discoveries, which have significantly advanced the field beyond the state of the art, such as those of feedback effects in T cell development, phenotypic reflux in B cell development, DNA biases in T and B cell receptor gene rearrangement and in class switch recombination, explanation of repertoire shift in antibody responses, and the role of lipid rafts in immunological synapses. Furthermore, the group has developed software tools for analyzing mutations in immunoglobulin (Ig) genes via the construction and quantification of mutational lineage trees. These tools have been shared with over 50 research groups worldwide, and the lab is currently one of the few which specialize in the study of lymphocyte development and repertoire dynamics using systems biology tools. BCR/antibody, a.k.a. immunoglobulin, and TCR genes are created through somatic gene rearrangement from gene segment libraries. Immunoglobulin genes are further diversified by somatic hypermutation and selection during the immune response. Studying the repertoires of these genes yields valuable insights into immune system function in infections, aging, autoimmune diseases and cancers. The introduction of high throughput sequencing has generated unprecedented amounts of repertoire and mutation data from immunoglobulin genes. However, common bioinformatics analysis programs are not appropriate for pre-processing and analyzing these data due to the lack of a template or reference for the whole gene. This has necessitated the development of unique software and tools for the analysis of products of what is now collectively called Adaptive Immune Receptor Repertoire (AIRR)-seq. Prof. Mehr was among the pioneers of this effort, and is now a member of the AIRR-community – a section of The Antibody Society devoted to developing standards for tools, data repositories and reporting of AIRR-seq studies.

The Team

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The Team

OUR RESEARCHERS

Prof. Shulamit Michaeli

Prof. Karl Skorecki

Prof. Sol EfroniThe Systems Biomedicine Laboratory

Prof. Tzipora C. Falik ZaccaiHuman Genetics

Dr. Orly AvniRegulation of gene expression in the immune system in health and disease.

Dr. Hava Gil-hennCancer Metastasis Analysis and Treatment

Dr. Evan ElliottMolecular and Behavioral Neuroscience

Dr. Meital Gal-tanamyMolecular Virology Laboratory

Dr. Marcela V. KarpujDirector, Genome Technology Center

Dr. Omry KorenMicrobiome Research Laboratory

Dr. David Enshell-seijffersStem cells in personalized medicine

Affiliate ResearchersAnnual Activity Report, March 2017

Prof. Eitan Okun

Prof. Cyrille J. Cohen

Prof. Ilanit Hasson-ohayon

Dr. Ron Piran

Prof. Shimon Weiss

Prof. Bilha Fischer

Prof. Orit Shefi

Dr. Nissan YissacharIntestinal neuro-immune-microbiome cross-talks, in health and disease

Dr. Ayal HendelA CRISPR Approach to Precision Medicine

Prof. David KarasikGenetics of Age-Related Musculoskeletal Diseases

Prof. Ronit SaridHerpesviruses

Dr. Milana Frenkel-MorgensternLiquid Biopsy Platform for Early Diagnostics of Brain Tumors

Dr. Amir BashanDiagnosis and personal treatments based on microbial ecology

Prof. Uri NirStratifying cancer patients according to their potential response to anti-metabolic drugs

Dr. Tomer KaliskySingle-cell genomics of kidney development, regeneration, and cancer

Prof. Noa VilchinskyThe Psycho-Cardiology Research Lab

Dr. Ronit IlouzMolecular and Cellular Mechanisms of Protein Kinasese in Neurodegenerative diseases

Prof. Nirit Bauminger-ZvielyAutism Spectrum Disorder (ASD) Research and Intervention Laboratory

Prof. Erez LevanonThe Mina and Everard Goodman Faculty of Life Sciences

Dr. Gur YaariComputational Systems Immunology Laboratory

Prof. Aron WellerDevelopmental Psychobiology Laboratory

Prof. Yanay OfranStudying the effects of genomic variations on protein function and interactions

Dr. Dana Atzil-SlonimClinical Research meets Analytic and Feedback Technologies (CRAFT)

Dr. Itay OnnChromosome Instability and Dynamics Laboratory

Prof. Mira Barda-SaadPersonalized Immunotherapy

Dr. Achia UrbachStem Cells and development Laboratory

Prof. Dror FixlerNano photonics, Fluorescence Imaging and Microscopy Research for Personalized Medicine

Prof. Ron UngerComputational Biology, Data Mining and Personalized Medicine

Dr. Nir Qvit

Prof. Cohen Haim

Prof. Liat Kulik

Dr. Rena Bina

Dr. Itay Koren

Dr. Shahar Alon

Prof. Gal YadidA proactive and personalized platform for treating psychiatric diseases

Prof. Yuval Garini

Prof. Chaya BrodieThe Mina and Everard Goodman Faculty of Life Sciences

Prof. Esther Adi-JaphaSchool of Education

Dr. Nitzan GonenFaculty of Life Sciences

Dr. Nitzan Gonen- The Mammalian Sex Determination Laboratory

Prof. Arnon BlumVascular Medicine and Endothelial Stem Cell Regulation

Prof. Eva Gilboa-Schechtman Department of Psychology and the Gonda Brain Science Center

Dr. Sivan Spitzer-ShohatAzrieli Faculty of Medicine

Dr. Sivan Spitzer-ShohatFaculty of Law

Prof. Yoram LouzounDepartment of Mathematics

Prof. Rachela PopovtzerNanotheranostics for Personalized Medicine

Prof. Yaron Shav-TalFaculty of Life Sciences

Prof. Noa Aharony Department of Information Science

Dr. Zohar MaorDepartment of General History

Prof. Ramit MehrFaculty of Life Sciences

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Phone Number

Email Address

Prof. Sol Efroni
The Systems Biomedicine Laboratory

Prof. Tzipora C. Falik Zaccai
Human Genetics

Dr. Orly Avni
Regulation of gene expression in the immune system in health and disease.

Dr. Hava Gil-henn
Cancer Metastasis Analysis and Treatment

Dr. Evan Elliott
Molecular and Behavioral Neuroscience

Dr. Meital Gal-tanamy
Molecular Virology Laboratory

Dr. Marcela V. Karpuj
Director, Genome Technology Center

Dr. Omry Koren
Microbiome Research Laboratory

Dr. David Enshell-seijffers
Stem cells in personalized medicine

Affiliate Researchers
Annual Activity Report, March 2017

Dr. Nissan Yissachar
Intestinal neuro-immune-microbiome cross-talks, in health and disease

Dr. Ayal Hendel
A CRISPR Approach to Precision Medicine

Prof. David Karasik
Genetics of Age-Related Musculoskeletal Diseases

Prof. Ronit Sarid
Herpesviruses

Dr. Milana Frenkel-Morgenstern
Liquid Biopsy Platform for Early Diagnostics of Brain Tumors

Dr. Amir Bashan
Diagnosis and personal treatments based on microbial ecology

Prof. Uri Nir
Stratifying cancer patients according to their potential response to anti-metabolic drugs

Dr. Tomer Kalisky
Single-cell genomics of kidney development, regeneration, and cancer

Prof. Noa Vilchinsky
The Psycho-Cardiology Research Lab

Dr. Ronit Ilouz
Molecular and Cellular Mechanisms of Protein Kinasese in Neurodegenerative diseases

Prof. Nirit Bauminger-Zviely
Autism Spectrum Disorder (ASD) Research and Intervention Laboratory

Prof. Erez Levanon
The Mina and Everard Goodman Faculty of Life Sciences

Dr. Gur Yaari
Computational Systems Immunology Laboratory

Prof. Aron Weller
Developmental Psychobiology Laboratory

Prof. Yanay Ofran
Studying the effects of genomic variations on protein function and interactions

Dr. Dana Atzil-Slonim
Clinical Research meets Analytic and Feedback Technologies (CRAFT)

Dr. Itay Onn
Chromosome Instability and Dynamics Laboratory

Prof. Mira Barda-Saad
Personalized Immunotherapy

Dr. Achia Urbach
Stem Cells and development Laboratory

Prof. Dror Fixler
Nano photonics, Fluorescence Imaging and Microscopy Research for Personalized Medicine

Prof. Ron Unger
Computational Biology, Data Mining and Personalized Medicine

Prof. Gal Yadid
A proactive and personalized platform for treating psychiatric diseases

Prof. Chaya Brodie
The Mina and Everard Goodman Faculty of Life Sciences

Prof. Esther Adi-Japha
School of Education

Dr. Nitzan Gonen
Faculty of Life Sciences

Prof. Arnon Blum
Vascular Medicine and Endothelial Stem Cell Regulation

Prof. Eva Gilboa-Schechtman
Department of Psychology and the Gonda Brain Science Center

Dr. Sivan Spitzer-Shohat
Azrieli Faculty of Medicine

Dr. Sivan Spitzer-Shohat
Faculty of Law

Prof. Yoram Louzoun
Department of Mathematics

Prof. Rachela Popovtzer
Nanotheranostics for Personalized Medicine

Prof. Yaron Shav-Tal
Faculty of Life Sciences

Prof. Noa Aharony
Department of Information Science

Dr. Zohar Maor
Department of General History

Prof. Ramit Mehr
Faculty of Life Sciences