Chapman Perelman Assistant Professor
Laboratory of Metabolic Regulation and Genetics
The Rockefeller University
Metabolic plasticity enables organisms to respond and adapt to changes in their environment. While the core components of most pathways of intermediary metabolism have long been described – consisting of ~3000 metabolic genes organized in pathways interconnected by 1000s of shared metabolites – it remains poorly understood how the flow of these metabolites is rewired in different metabolic states. This question is particularly relevant in the context of tumors, as cancer cells are frequently starved for nutrients and exposed to toxic waste products due to a combination of increased nutrient consumption and dysfunctional vasculature. In the Birsoy lab, we combine a number of cutting-edge techniques – from the development of forward genetics tools (i.e. CRISPR-Cas9 technology) to metabolomics – to elucidate how metabolism contributes to tumor formation and metastasis.
Our long term research goal is to understand how metabolic pathways in cancer cells are rewired by their nutrient environment and, further, to determine whether these pathways present metabolic liabilities that could be exploited for anti-cancer therapy.
Dr. Kivanc Birsoy received his undergraduate degree in Molecular Genetics from Bilkent University in Turkey in 2004 and his Ph.D. from the Rockefeller University in 2009, where he studied molecular genetics of obesity in the laboratory of Jeffrey Friedman. In 2010, he joined the laboratory of David Sabatini at the Whitehead Institute of Massachusetts Institute of Technology (MIT). There, he combined forward genetics and metabolomics approaches to understand how different cancer types rewire their metabolism to adapt nutrient deprived environments. He also used similar approaches to study how mitochondrial dysfunction influences cellular metabolism. In 2015, Kivanc joined the Rockefeller faculty as a Chapman-Perelman Assistant Professor. His research focuses on how cancer cells rewire their metabolic pathways to adapt to the environmental stress conditions during tumorigenesis. He is the recipient of numerous awards, incluuding the Leukemia and Lymphoma Society Special Fellow award, Margaret and Herman Sokol Award, NIH Career Transition Award, Irma Hirschl/Monique Weill-Caulier Trusts Award, Sidney Kimmel Cancer Foundation Scholar Award, March of Dimes Basil O’Connor Scholar Award, AACR NextGen award for Transformative Cancer Research, Searle Scholar, Pew-Stewart Scholarship for Cancer Research and NIH Director’s New Innovator Award.
Identification of cell-specific metabolites limiting for metastatic colonization
Cancer cells often metastasize to distant organs resulting in the majority of deaths in cancer patients. To survive in these host organs, cancer cells require substantial metabolic alterations to obtain sufficient amounts of nutrients. However, metabolic and nutrient requirements of cancer cells to metastasize and grow in different organs are mostly unclear. We recently identified the amino acid aspartate as one such nutrient limitation for tumor growth. In this proposal, we would like to determine why this amino acid (aspartate) is required in cancer cell proliferation and metastasis.
“It is an honor to receive the Pershing Square Sohn Award alongside many other accomplished scientists. This award will enable us to delve into fields that are impossible to explore through conventional funding sources.”
In addition to aspartate, our serum contains many more small molecules and nutrients. To systematically identify other nutrient limitations, we developed a method and can determine metabolic features of single cell types in tumors. These studies will provide insights into which nutrients cancer cells need to metastasize and lead to the development of novel therapies based on metabolic features.
“We are mostly driven by our curiosity, which is justification enough to pursue a scientific question.”