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Amit Tirosh, MD

Amit Tirosh, MD

Grant Status

Sheba Medical Center/ Tel Aviv University

Grant Type
Clinical Research Career Development Award (CRCDA)

Project Title
The role of oncometabolites in von Hippel Lindau-related pancreatic cancer

Tumor Types

Research Topics
Pancreatic Cancer

About the Investigator:

Dr. Tirosh is an expert in the genetics of endocrine tumors and their clinical management. He received his MD degree from the Hebrew University of Jerusalem, was a Resident in Internal Medicine and Endocrinology at Assaf-Harofe and Rabin Medical Centers in Israel, and then a Fellow in Genetics of Endocrine Disease and Cancer Bioinformatics at the National Cancer Institute of the US National Institutes of Health. He is currently Head of the Neuroendocrine Oncology Genomics Laboratory at Sheba-Tel HaShomer Hospital and an Associate Professor of Medicine in the Sackler Faculty of Medicine at Tel Aviv University.

About the Research:

von Hippel-Lindau syndrome is a rare disease that causes tumors and cysts to grow in the body, at sites including the brain and spinal cord, kidneys, pancreas, and adrenal glands. The tumors are usually benign (non-cancerous); but, some tumors, such as those in the pancreas and kidney, can become cancerous. von Hippel-Lindau disease is caused by mutations in the VHL gene, which normally functions to prevent cells from growing and dividing too rapidly or in an uncontrolled way. This gene normally functions to enable cells to sense levels of oxygen, and cells with a mutant VHL gene falsely sense low oxygen levels. Dramatic changes in the pathways that cells use to metabolize nutrients occur during the development of cancer. These changes can affect both cell growth and the immune response to the tumor. Dr. Tirosh has found that distinct changes in metabolism characterize pancreatic tumors that developed in individuals with von Hippel-Lindau disease, and he has identified a specific small molecule metabolite that may mediate the effects of the VHL mutation. Dr. Tirosh hypothesizes that this small molecule is a pro-tumor metabolite, that accelerates tumor proliferation and suppresses the immune response to the tumor in pancreatic cancer patients with VHL. His team will test these hypotheses. If correct, this small molecule is a potential target for treatment of pancreatic cancers (and possibly other cancers) in VHL patients.


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