Institution: Tel Aviv University
Grant Type: Project Grant
Award Year: 2024–2027
Research Topics: Chloride intracellular channel proteins (CLICs)

Dr. Haitin’s research focuses on the structure-function relationships governing the activity of critical cellular enzymes in health and disease. Following graduation from the Interdisciplinary Life and Medical Sciences Program at Tel Aviv University, he pursued a PhD in the field of electrophysiology, studying the properties of ion channels involved in aberrant cardiac function and cancerous transformation. After postdoctoral training as a structural biologist at the University of Washington, Seattle, he returned to Tel Aviv University, where he is now an Assistant Professor in the Department of Physiology and Pharmacology at the Sackler Faculty of Medicine.

About the Research

Cancer cells have been shown to depend on cues from their local environment in order to thrive. The ability of tumor cells to evade the immune response and resist therapy has been a long-standing hurdle in the fight against cancer. Chloride intracellular channel proteins (or CLICs) have recently gained attention in cancer research due to their involvement in cell growth, death, and movement.

Dr. Haitin’s current research project focuses on CLICs. While their exact function in cancer formation is still unknown, the involvement of CLICs was recently found in glioblastoma and ovarian cancer cells, thus rendering these proteins as potential novel oncology biomarkers.

Recently, the Haitin team discovered that CLICs can cause membrane fusion, a process influenced by various cellular conditions in the tumor environment and known to drive cancer. They will now try to uncover the molecular basis of this process, as well as study the ability of CLICs to enable cancer cells to communicate with their local environment. By utilizing molecular structure-function studies, the Haitin lab hopes to illuminate the pathophysiological role of CLIC proteins in the cancerous process. Their research should provide a firm stepping-stone for the future development of novel diagnostic tests and therapies.

Institution: Tel Aviv University
Grant Type: Project Grant
Award Year: 2025–2028
Research Topics: Breast Cancer

Prof. Ran Elkon studies the genetic mechanisms that affect our risk for developing complex diseases. He received his BSc in Physics and MSc and PhD in Bioinformatics from Tel Aviv University. After postdoctoral training at the Netherlands Cancer Institute (NKI, Amsterdam) he returned to Tel Aviv University, and joined the Human Molecular Genetics Dept. at the School of Medicine, where he is now an Associate Professor.

About the Research

Women who carry a mutation in the BRCA1 gene have a markedly increased risk for breast cancer (BC). Current management options for such BRCA1 carriers range from intensive early-age BC screening to risk-reducing surgical removal of the breasts and ovaries. These surgical choices are irreversible and have substantial adverse side effects. Importantly, age at BC diagnosis among BRCA1 carriers shows high variation: some develop BC before the age of 35 yrs. while other carriers remain BC-free even after the age of 60 yrs. This high variation indicates the existence of risk-modifying factors. However, our limited understanding of such modifiers precludes clinical decision-making that is based on the specific risk of each carrier. Therefore, there is a major clinical need for refined risk models for BRCA1 carriers. This is especially important in Israel, since Ashkenazi Jews (AJ) is the ethnic group with the highest prevalence of BRCA1 carriers among all the world populations.

The goal of our research is to systematically discover novel genetic BC-risk modifiers for BRCA1 carriers, thereby improving BC risk prediction models for these women. By recruiting a large cohort of Israeli AJ women who carry BRCA1 mutation and sequencing their entire genomes, we will discover a variety of genetic variants that modify BC risk for BRCA1 carriers. Together with known non-genetic BC risk factors that will be collected in our cohort, we will apply cutting-edge computational methods to build an integrative BC-risk prediction model for BRCA1 carriers. This study will constitute an essential milestone towards the implementation, in the Israeli healthcare system, of personalized risk-based decision support tools for BRCA1 carriers.

Institution: Tel Aviv University
Grant Type: Project Grant
Award Year: 2024–2027
Research Topics: Brain Cancer, Cancer Metastasis

Prof. Stein’s research centers on how the tumor microenvironment affects tumor growth, focusing on brain tumors. He received his BSc and PhD from the Hebrew University of Jerusalem. After postdoctoral training at the College of Physicians and Surgeons at Columbia University in New York, he returned to Tel Aviv University, where he is now a Professor of Neurobiology in the George S. Wise Faculty of Life Sciences.

About the Research

Besides transformed cancer cells, the tumor mass contains non-cancerous cells recruited to the tumor region to regulate its progression. The recruited cells are collectively termed “tumor microenvironment (TME) cells.” In the brain, these cells mainly comprise an immune cell type termed “macrophage.”

Brain macrophages reside in the brain and help protect it from harm. They can be either resident macrophages or ones from the blood, called monocyte-derived macrophages. The resident macrophages are made up of two types: microglia, that regulate brain development, maintenance of neuronal networks, and injury repair; and border-associated macrophages (BAM), which reside near the border of the brain. While there is much knowledge regarding how microglia and blood-derived macrophages affect brain tumors, little is known about BAM’s role in brain metastasis. Owing to their strategic geographic position in close proximity to blood vessels that penetrate the brain, these cells may potentially play a role in the establishment and progression of brain metastases.

Prof. Stein’s research aims to test this hypothesis and unravel the underlying processes, using a multidisciplinary approach combining state-of-the-art mouse models and ex vivo and in vivo imaging systems. This study may identify new brain metastasis regulators, clarify how the TME regulates this devastating and currently incurable disease and, perhaps, identify new therapeutic targets.

Institution: The Hebrew University of Jerusalem
Grant Type: Project Grant
Award Year: 2025–2028
Research Topics: Breast Cancer, Ovarian and Uterine Cancer

Prof. Eilon Sherman is an associate Professor and PI at the Hebrew University, and the director of a Minerva center. He is an established leader in biophysics, with an interdisciplinary background, and expertise in the pioneering, development and application of super resolution microscopy to study signaling in multiple cell types, esp. in T cells and in cancer cells.

About the Research

Breast cancer is one of the most common cancers affecting women worldwide, though it can also occur in men. Early detection through screening methods such as mammography and advances in treatments, including surgery, radiation, chemotherapy, hormone therapy, and targeted therapies, have significantly improved outcomes. Current treatments, including surgical, chemotherapy and immunotherapic strategies have improved long-term outcomes, but their benefit remains very limited. Thus, additional strategies for treatment are urgently needed.

T cells expressing chimeric antigen receptors (CAR-Ts) are an emerging tool for cancer treatment, and hold the promise for treatment of a wide variety of cancers and other diseases. Indeed, adoptive immunotherapy of CAR-Ts is currently under preclinical and clinical testing for treating mainly blood cancers. Unfortunately, CAR-Ts are still not available for treating solid cancers, and still suffer from grave side effects, limited efficay (esp. against solid tumors), cell exhaustion and senecence, long production time, and a prohibitively high cost, at ~$1Million per treatment.

Here, I propose to develop a novel framework that will enable optimal design of CARs that target a common marker of breast cancers, called HER2. The framework will include new experimental data from an in-depth and systematic biophysical study, integrative and predictive modelling of CAR signaling. The study will be based on super-resolution imaging of the synapse between CAR-Ts and target cancer cells and with patient-derived tumor organoids. The combination of the propopsed techniques will allow to improve on CAR design in terms of their cancer-related functions, such as efficacy, safety and infiltration capacity.

Institution: Weizmann Institute of Science
Grant Type: Project Grant
Award Year: 2025–2028
Research Topics: Pancreatic Cancer

Prof. Yardena Samuels received her BSc from Cambridge University, UK and an MSc in immunology at the Hebrew University of Jerusalem. She completed a PhD at Imperial College, London and performed a postdoctoral fellowship at Johns Hopkins University. She served as an Assistant Professor at NIH before joining the Weizmann Institute in 2012. Today, she is the director of the Moross Integrated Cancer Center, the recipient of the Pezoller Foundation Award, the Youdim Family Prize for Excellence in Cancer Research, the Sergio Lombroso Award in Cancer Research, an EMBO member, and is President of the European Association for Cancer Research.

About the Research

Immunotherapy has emerged as a groundbreaking approach to cancer treatment. However, the majority of metastatic patients are unresponsive. This proposal focuses on a novel approach in cancer immunotherapy, TCR-T therapy, targeting a mutation known as KRAS G12V/C, found mostly in lung, pancreatic, and colon cancers and is notoriously difficult to treat effectively with current therapies. Prof. Samuel’s team made significant strides in identifying a new potential treatment target—a small piece of protein, or neoantigen, directly created by the KRAS G12V/C mutation. She demonstrated that this neoantigen can be presented by cancer cells to the immune system and activate it. Moreover, the team isolated T-cells from donors that recognize this neoantigen, identified the T cell receptor in charge of the recognition, and engineered other donor T-cells to enhance their ability to kill cancer cells carrying the KRAS G12V/C mutation. Her team is developing additional treatment modalities against KRAS G12V/C mutated cancers, including cancer vaccines and bispecific antibodies. Furthermore, she demonstrated the synergistic effect of combination therapy of chemotherapy and the lab’s engineered T-cells. The team aims to evaluate several treatment combinations against this neoantigen and refine the best option to pursue in clinical trials in novel mice models. This work on KRAS G12V/C could impact the treatment of ~120,000 patients yearly who suffer from these cancer types, and pave the way for future therapies that can target other mutation-derived neoantigens, offering new treatment options for many more patients.

Institution: Technion, Israel Institute of Technology
Grant Type: Project Grant
Award Year: 2025–2028
Research Topics: Bone Cancers, Carcinomas, Sarcoma, Skin Cancer

Prof. Amir Orian received his MD (1999), and PhD (2000) from the Technion’s Rappaport Faculty of Medicine. Mentored by Nobel Laureate Professor Aaron Ciechanover, he investigated mechanisms involved in ubiquitin-dependent activation of the immune system. As a post-doctoral fellow at FHCRC Seattle WA ,together with Rober Eisenman he studied the action and regulation of the Myc oncogene, which is intimately involved in cancer. In 2005 he returned to the Faculty of Medicine, Technion and was the Head of Dpt. of cancer biology and is currently the director of the Technion’s integrative cancer research center (RTICC) . He is a recipient of excellence prizes including: the Clore foundation fellowship, and the Fulkes fellowship for MD/PhD. Amir was special fellow of the HFSP and Lymphomas and Leukemia Society. He is a recipient of the Alon-ISF fellowship for young scientist, and the HFSP-CDA award. He is a recipient of the Krill Award for outstanding young scientists. His laboratory enjoyed the generous support of three ICRF project grants.

About the Research

The Orian lab focuses on understanding fundamental mechanisms that regulates cell’s identity and cancer development and translating discoveries to diagnostic tools and future therapies:

“Oncoprotein stabilization in cancer”: While the ubiquitin pathway was discovered as a pathway that regulate protein degradation, the Orian Lab discovered that a ubiquitin-dependent pathway is essential for stabilization of cancer promoting genes and is active predominantly in cancer cells. The pathway is critical for tumorigenesis and confers resistance to molecular therapy. The lab study this pathway; from its biochemistry via experimental cancer systems to clinical studies, and are developing PROTAC-like degraders to eliminate the pathway’s enzymes. The lab investigate hard-to treat cancers: sarcoma and therapy resistant melanoma, using multiple experimental tools including cancer genetics, functional screens, genomics, biochemistry and cancer cell biology mouse-models of human cancer and tightly connect basic research to the clinic using patient-derived specimens and data.

More about the lab can be found at: https://orian.net.technion.ac.il.

Institution: Hebrew University of Jerusalem
Grant Type: Project Grant
Award Year: 2024–2027
Research Topics: Pancreatic Cancer

Prof. Nussbaum’s research focuses on how bacteria associated with chronic oral inflammation interact with cancer cells. He received his MD and PhD degrees from the Albert Einstein College of Medicine in New York and trained in internal medicine before transitioning to a post-doctoral fellowship at the Weizmann Institute in Israel. He is now a full Professor in the Institute of Biomedical and Oral Research at the Hebrew University’s Dental Faculty.

About the Research

Pancreatic cancer is a severe disease often found in people without any known risk factors. Recent research suggests that bacteria from periodontal disease, a common chronic mouth inflammation, might be a new risk factor for pancreatic cancer. Prof. Nussbaum’s previous work showed that a specific type of bacteria linked to periodontal disease can move from the mouth to the pancreas, causing pre-cancerous changes in the pancreatic tissue. When he combined this bacterial infection with a genetic mutation associated with pancreatic cancer risk, he discovered that the bacteria and the mutation together sped up the development of pancreatic cancer. This suggests that these bacteria might play a direct role in causing pancreatic cancer.

The Nussbaum lab aims to understand how oral bacteria are connected to pancreatic cancer. They found these bacteria inside the cells of developing pancreatic tumors and will use advanced techniques to identify which cells are infected and how these bacteria affect the gene activity of these cells. Using patient-derived cell cultures, they will investigate the genetic mutations that allow bacteria to infect and stay in the tumors. Since these bacteria thrive in nutrient-poor conditions, they will also study the metabolic pathways of cancer cells that harbor these bacteria.

The research performed by Prof. Nussbaum and his team should lead to a detailed understanding of how bacteria inside cells contribute to pancreatic cancer, potentially leading to new treatment options for patients.

Institution: Weizmann Institute of Science
Grant Type: Project Grant
Award Year: 2025–2028
Research Topics: Colorectal Cancer, Lung Cancer, Pancreatic Cancer, Pediatric Cancer

Dr. Nir London completed his PhD in computational structural biology at the Hebrew University of Jerusalem and post-doctoral fellowship at UCSF. Dr. London joined the Weizmann Institute of Science in 2015, where his lab is focused on covalent chemical biology and is developing new technologies to discover and functionalize covalently acting compounds. His honors include the Alon fellowship, the 2021 EFMC award for young medicinal chemist in academia and the 2021 ISCB award for young chemical biologist.

About the Research

Cell growth and division are tightly controlled by a complex network of proteins that regulate these processes within and outside of cells. Disruptions or mutations in these proteins can lead to uncontrolled cell growth, resulting in cancer. Among the most significant oncogenic proteins is KRAS, where mutations keeping it in a continuously active state are frequently found in various cancers. These mutations are particularly prominent in pancreatic cancer. Developing molecules that can bind to and inhibit these active KRAS mutants are therefore a crucial goal for treating pancreatic and many other cancers.

Dr. London’s laboratory specializes in the development of covalent inhibitors, which are a type of molecule that binds irreversibly to a target protein. This project seeks to develop covalent inhibitors for KRAS G12D, the most common KRAS mutant in cancer. A major breakthrough recently occurred with the development of effective covalent inhibitors for G12C – a different, less abundant mutant. Prior to this, KRAS had long been considered “undruggable” due to its small size and other factors. Now, based on the structure of these molecules and using computational tools for inhibitor design developed by the lab, Dr. London will design, synthesize and test molecules with chemical groups that will react specifically with the G12D mutant. His team will select the best binders discovered in their initial experiments and test whether they inhibit KRAS G12D in cells and in biological experiments. The molecules developed will contribute the study of KRAS G12D biology and form a basis for the develop of potent drugs targeted against the G12D mutation. This research offers new hope for more efficacious and less toxic treatments urgently needed for treating pancreatic and other KRAS G12 cancers.

Institution: Technion, Israel Institute of Technology
Grant Type: Project Grant
Award Year: 2024–2027
Research Topics: Breast Cancer

Prof. Kimmel’s main research interests lie in the realms of computer vision, machine learning, medical imaging, and scientific computation. He received his BSc, MSc, and DSc/PhD degrees from The Technion, and then performed postdoctoral research at Lawrence Berkeley National Laboratory and the Department of Mathematics at the University of California, Berkeley. When he returned to Israel, he founded and heads the Geometric Image Processing (GIP) Lab at The Technion, where he is presently a full Professor. His current focus is on digital pathology and computational oncology.

About the Research

Breast cancer is the most common cancer diagnosed in women worldwide and the leading cause of cancer-related deaths among women. Women over forty are advised to have regular checkups that often include testing a biopsy sample for proteins linked to tumor growth and survival.

In recent years, the FDA has recommended using digitally scanned biopsy slides for clinical evaluations. Digital systems, particularly those using deep learning, have significantly improved many aspects of life, including medical diagnostics. Prof. Kimmel believes that AI systems, which can analyze large amounts of data from clinical trials, will enhance prognostic evaluations and help doctors choose better treatments. AI systems are often more accurate than human observations and decision-making.

The Kimmel team proposes to test an AI system to improve the consistency, relevance, efficiency, and accuracy of cancer subtyping, which should help tailor treatments to individual patients. The system will require only a digital scanner and internet access, making advanced analysis of biopsy samples possible in any clinic, even in areas with limited medical resources. The results of this study should eventually lead to enhanced pathological methods, better prognostic tools for oncologists, and should ultimately improve the quality of life for patients worldwide.

Institution: Hebrew University of Jerusalem
Grant Type: Project Grant
Award Year: 2025–2028
Research Topics: Oral Cancer

Prof. Avi-Hai Hovav earned a PhD in Immunology and Microbiology from the Hebrew University in 2005, followed by postdoctoral training at Harvard University. In 2008, he returned to Hebrew University as a Lecturer, advancing to Senior Lecturer in 2011, Associate Professor in 2014, and Full Professor in 2019. Dr. Hovav’s research centers on the development and function of the oral mucosal immune system, with a focus on the oral epithelium and its key sentinel cells, Langerhans cells. His laboratory employs murine models to investigate the mechanisms driving oral cancer development, aiming to translate these findings to human disease for therapeutic insights.

About the Research

Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer and a leading cause of cancer-related death. Tumors with higher nerve density are often more aggressive and linked to increased metastasis, pain, and poorer survival. However, the factors driving nerve growth in tumors remain unclear. Our research focuses on immune cells in the oral lining that regulate nerve growth, particularly Langerhans cells (LCs) and macrophages. Our preliminary studies revealed that LCs maintain healthy nerve density by releasing IL-1β, which stimulates Nerve Growth Factor (NGF) production in epithelial cells. However, in OSCC, LCs are depleted and replaced by macrophages, which produce higher levels of NGF, leading to excessive nerve growth that may fuel tumor progression.

We hypothesize that early in OSCC, LCs regulate nerve growth to support immune defense. As OSCC advances, LCs are replaced by macrophages, driving excessive nerve growth and promoting cancer progression. To test this, we will: (1) study how nerve density impacts early OSCC growth; (2) explore how macrophages drive nerve growth and tumor aggressiveness; (3) assess how increased nerve density shapes the tumor environment; and (4) validate our findings in human OSCC tissues. Our innovative approach highlights a previously unrecognized role for immune cells in controlling nerve growth in OSCC. This work could lead to new treatments that limit nerve-driven cancer progression, improving outcomes for OSCC patients.