Exposing Vulnerabilities in Cancer Metabolism: New Discoveries

Organizers

Lydia Finley, PhD

Memorial Sloan-Kettering Cancer Center

Lydia Finley is the Jack Sorrell Fellow of the Damon Runyon Cancer Research Foundation and a postdoctoral fellow in the laboratory of Craig Thompson at Memorial Sloan Kettering Cancer Center. She earned her PhD in the laboratory of Marcia Haigis at Harvard Medical School. Her research focuses on understanding how signaling events regulate intracellular metabolic pathways and how metabolites influence chromatin state and cell fate decisions.

Steven S. Gross, PhD

Weill Cornell Medical College

Dr. Steven S. Gross is Professor of Pharmacology, Director of Advanced Training in Pharmacological Sciences, and Metabolomics Lab Director at Weill Cornell Medical College. His major research interest over the past two decades has been elucidating mechanisms of cell signaling by reactive molecules, with a primary focus on the physiological chemistry and biology of nitric oxide (NO). Work on NO has culminated in over 170 published papers, 25 issued US patents, and the founding of a biotech start-up that conducted a multinational phase III clinical study to test the therapeutic efficacy of a NO synthase (NOS) inhibitor for a life-saving cardiovascular indication. With Nobel Laureates in the field, Dr. Gross founded the NO Society. Since reactive molecules typically mediate their cell signaling actions by engaging in covalent reactions with proteins, he sought to develop proteomic approaches that can be used to define and inventory various NO-mediated protein modifications. These efforts led to an interest in biological mass spectrometry (MS) and his establishment in 1997 of the MS core facility at Weill Cornell Medical College. His lab acquired broad experience and know-how in bioanalytical techniques for protein and small molecule analysis –including a robust platform for untargeted metabolite profiling and development of an untargeted stable isotope tracing technology.

Costas Andreas Lyssiotis, PhD

University of Michigan

Costas A. Lyssiotis obtained his bachelor's degree in chemistry and biochemistry from the University of Michigan in 2004 and his PhD in Chemical Biology from The Scripps Research Institute in 2010. Costas joined the laboratory of Lewis C. Cantley at Harvard Medical School as the Amgen fellow of the Damon Runyon Cancer Research Foundation and was later awarded a Pancreatic Cancer Action Network Pathway to Leadership Grant. Dr. Lyssiotis is currently an Assistant Professor at the University of Michigan Medical School with appointments in the Departments of Physiology and Medicine. His lab studies the biochemical pathways and metabolic requirements that enable tumor survival and growth and, in particular, how this information can be used to design targeted therapies. He is a Lefkofsky Scholar, a Kimmel Scholar a Dale F. Frey Breakthrough Scientist and was awarded the Tri-Institutional Breakout Prize for Junior Investigators.

Sonya Dougal, PhD

The New York Academy of Sciences

Caitlin McOmish, PhD

The New York Academy of Sciences

Speakers

Kivanc Birsoy, PhD

The Rockefeller University

Kivanc Birsoy received his undergraduate degree in Molecular Genetics from Bilkent University in Turkey in 2004 and his PhD 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, Dr. Birsoy joined the Rockefeller faculty as an Assistant Professor. He is a recipient of Jane Coffin Childs Medical Fund Fellowship, Leukemia and Lymphoma Society Special Fellow award, Searle Scholar award, Sidney Kimmel Foundation award and NIH Career Transition award.

David A. Foster, PhD

Hunter College of the City University of New York

David Foster is the Rosalyn Yalow Professor in the Department of Biological Sciences at Hunter College of the City University and holds an adjunct faculty position in the Department of Pharmacology and Weill Cornell Medicine where his lab recently moved. He received his Bachelor's degree in Biochemistry from the University of California at Berkeley and his PhD from Columbia University where he studied DNA synthesis with Geoffrey Zubay. His postdoctoral studies were worked in the lab of Saburo Hanafusa at the Rockefeller University where he worked with RNA tumor viruses expressing oncogenic tyrosine kinases. Upon establishing his own lab, he began investigating the intracellular signals that are activated by oncogenic tyrosine kinases and discovered that a common target of these signals is the enzyme phospholipase D (PLD). Elevated PLD expression and activity has subsequently been found in virtually every cancer where it has been examined. The metabolite generated by PLD is phosphatidic acid (PA), which is required for mTOR and much of his work over the past 15 years has been examining the PA-mTOR signaling axis in human cancer cells. His work has also involved dysregulated metabolic control of cell cycle progression in cancer cells.

Steven S. Gross, PhD

Weill Cornell Medical College

Dr. Steven S. Gross is Professor of Pharmacology, Director of Advanced Training in Pharmacological Sciences, and Metabolomics Lab Director at Weill Cornell Medical College. His major research interest over the past two decades has been elucidating mechanisms of cell signaling by reactive molecules, with a primary focus on the physiological chemistry and biology of nitric oxide (NO). Work on NO has culminated in over 170 published papers, 25 issued US patents, and the founding of a biotech start-up that conducted a multinational phase III clinical study to test the therapeutic efficacy of a NO synthase (NOS) inhibitor for a life-saving cardiovascular indication. With Nobel Laureates in the field, Dr. Gross founded the NO Society. Since reactive molecules typically mediate their cell signaling actions by engaging in covalent reactions with proteins, he sought to develop proteomic approaches that can be used to define and inventory various NO-mediated protein modifications. These efforts led to an interest in biological mass spectrometry (MS) and his establishment in 1997 of the MS core facility at Weill Cornell Medical College. His lab acquired broad experience and know-how in bioanalytical techniques for protein and small molecule analysis –including a robust platform for untargeted metabolite profiling and development of an untargeted stable isotope tracing technology that will be the focus of his NYAS presentation.

Marcia Haigis, PhD

Harvard Medical School

Marcia C. Haigis obtained her PhD in Biochemistry from the University of Wisconsin in 2002. She then performed postdoctoral research at MIT studying mitochondrial regulation and aging. In 2006, Dr. Haigis joined the faculty of Harvard Medical School, where she is currently an Associate Professor in the Department of Cell Biology. Additionally, Dr. Haigis is an active member of the Paul F. Glenn Laboratories for Medical Research and organizes a Boston Area Aging Data community. Her current work contributes to the molecular understanding of how mitochondria regulate cellular stress responses in cancer. For her work, Dr. Haigis has received a Brookdale Leadership in Aging Award, the Ellison Medical Foundation New Scholar Award and an American Cancer Society Research Scholar Award.

Kayvan R. Keshari, PhD

Memorial Sloan Kettering Cancer Center

Dr. Kayvan R. Keshari received degrees in Biochemistry, Mathematics and Biomedical Engineering from the University of California, Berkeley and University of North Carolina, respectively, after which he completed postdoctoral training at the University of California, San Francisco (UCSF) in Biomedical imaging and Bioengineering under the supervision of Dr. John Kurhanewicz. He is currently an Assistant Member and Laboratory Head at Memorial Sloan Kettering Cancer Center, with appointments in both the Department of Radiology and the Molecular Pharmacology Program. He is a professor in the Gerstner Sloan Kettering School of Biomedical Sciences and in multiple departments with Cornell University including Chemical Biology and Biochemistry. At MSK, Dr. Keshari's lab focuses on the interrogation of cancer metabolic processes and advanced multi-modality imaging, with special emphasis in the field of hyperpolarized MRI. With changes in cancer metabolism as the driving force, the lab's biochemical investigation is centered on oxidative stress and changes in redox, as well as the rates of biochemical reactions in vivo, which are related to cancer aggressiveness and response to therapeutics. The long-term goal of which is to bring some of these novel mechanisms to the clinic and make an impact on both diagnosis and therapy.

Brendan D. Manning, PhD

Harvard T.H. Chan School of Public Health

Brendan Manning is a Professor in the Department of Genetics and Complex Diseases at Harvard University's T.H. Chan School of Public Health, Director of the PhD Program in Biological Sciences in Public Health at Harvard's Graduate School of Arts and Sciences, and a Faculty Member of the Dana-Farber/Harvard Cancer Center. Dr. Manning received his BS from the University of Massachusetts, Amherst and his PhD from Yale University in 2000. He then joined the laboratory of Lewis Cantley at Harvard Medical School for his postdoctoral research. During this time, he discovered that the tuberous sclerosis complex (TSC) tumor suppressors serve as the molecular connection between the PI3K and mTOR pathways, thereby linking a signaling pathway activated in the majority of human cancers to a nutrient-sensing pathway that controls cell growth and metabolism. In 2004, he joined the faculty of the then newly established Department of Genetics and Complex Diseases at Harvard to continue research at the interface of cancer and metabolism. In 2015, Dr. Manning became an inaugural recipient of the National Cancer Institute's Outstanding Investigator Award.

Joshua Rabinowitz, MD, PhD

Princeton University

Joshua Rabinowitz grew up in Chapel Hill, North Carolina. In 1994, he earned BA degrees in Mathematics and Chemistry from the University of North Carolina. From there, he moved west to Stanford, where he earned his PhD in Biophysics in 1999, followed by his MD in 2001. In 2000, he co-founded Alexza Pharmaceuticals leading R&D efforts there for four years, eventually resulting in FDA approval of the first thermal aerosol drug delivery product, the Adasuve inhaler. In 2004, Joshua joined the faculty of Princeton University, where he established a leading research group in the area of metabolomics. His lab has developed innovative ways to use isotope tracers to map metabolic flows (fluxes), and has blended these technologies with state-of-the-art genetics and computation to reveal normal metabolic regulation and dysregulation in disease. These technologies have contributed to important biomedical advances, including the discovery of the oncometabolite 2-hydroxyglutarate, and to the founding of multiple companies, most recently Raze Therapeutics. Joshua is author of more than 100 papers and the inventor of over 100 patents.

David M. Sabatini, MD, PhD

Whitehead Institute

David Sabatini is a Member of the Whitehead Institute for Biomedical Research, Senior Associate Member at The Broad Institute MIT, and Member of the Koch Institute for Integrative Cancer Research at MIT, as well as a Professor of Biology at the Massachusetts Institute of Technology. He is also Investigator of the Howard Hughes Medical Institute. David received his BS from Brown University magna cum laude and his MD/PhD from Johns Hopkins University in 1997. He completed his thesis work in the lab of Dr. Solomon H. Snyder in the Department of Neuroscience. Later in the same year, David was appointed a Whitehead Fellow at the Whitehead Institute for Biomedical Research. This was followed in 2002 by a dual appointment as a Member at the Whitehead Institute and Assistant Professor of Biology at the Massachusetts Institute of Technology. David has received a number of distinctions, including being named a W. M. Keck Foundation Distinguished Young Scholar, a Pew Scholar, a TR100 Innovator, a recipient of the 2009 Paul Marks Prize for Cancer Research, 2012 The Earl and Thressa Stadtman Scholar Award from ASBMB, 2013 Feodor Lynen Award from Nature, the 2014 NAS Award in Molecular Biology, the 2014 Colin Thomson Memorial Medal, and most recently, he was named the Alexander M. Cruickshank Lecturer at the Gordon Research Conference on Lysosomal Diseases, Galveston, TX.

David and his lab at the Whitehead Institute study the basic mechanisms that regulate cell growth, the process whereby cells and organisms accumulate mass and increase in size. These pathways are often deranged in human diseases, such as diabetes and cancer. A major focus of the lab is on a cellular system called the Target of Rapamycin (TOR) pathway, a major regulator of growth in many eukaryotic species. Work in David's lab has led to the identification of many components of the pathway and to an understanding of their cellular and organismal functions. David is also interested in the role of metabolism in cancer and in the mechanisms that control the effects of dietary restriction on tumorigenesis. In addition to the work on growth control and cancer, David's lab has developed and is using new technologies that facilitate the analysis of gene function in mammalian cells. The lab developed 'cell-based microarrays' that allow one to examine the cellular effects of perturbing the activity of thousands of genes in parallel. David is a founding member of The RNAi Consortium (TRC) of labs in the Boston area that is developing and using genome-scale RNA interference (RNAi) libraries targeting human and mouse genes.

Eileen White, PhD

Rutgers University

Dr. Eileen White received her Bachelor of Science degree from Rensselaer Polytechnic Institute followed by a PhD in Biology from SUNY Stony Brook. She went on to be a Damon Runyon Postdoctoral fellow in the laboratory of Dr. Bruce Stillman and then to a Staff Investigator position at Cold Spring Harbor Laboratory. There she discovered that one of the oncogenes of the DNA tumor virus adenovirus encoded an inhibitor of programmed cell death or apoptosis (E1B 19K) that this gene was a viral homologue of the human BCL-2 oncogene. She went on to establish that oncogene activation that deregulates cell growth also activates apoptosis, and that coordinate inhibition of apoptosis is an important function that promotes cancer. These findings revealed roles for the p53 tumor suppressor in activating apoptosis and suppressing cancer and for the Bcl-2-related anti-apoptotic proteins blocking apoptosis and promoting cancer.

Dr. White continued her work defining the role and mechanisms of apoptosis regulation in cancer at Rutgers University where she is currently the Deputy Director and Associate Director for Basic Science at the Rutgers Cancer Institute of New Jersey, an NCI-designated Comprehensive Cancer Center. She is also a Distinguished Professor of Molecular Biology and Biochemistry. Dr. White has served on the Board of Scientific Counselors of the National Cancer Institute and other review panels for the National Institutes of Health. She is the recipient of numerous awards including a MERIT award from the National Cancer Institute, the Red Smith award from the Damon Runyon Cancer Research Foundation, a Howard Hughes Medical Institute Investigatorship, an Achievement Award from the International Cell Death Society, a Career Award for the European Cell Death Organization, and is an elected Fellow of the American Society of Microbiology (ASM) and the American Association for the Advancement of Science (AAAS). Dr. White has also served as a member of the Board of Directors of the American Association for Cancer Research (AACR), the Scientific Review Boards for the Starr Cancer Consortium, the Damon Runyon Cancer Research Foundation, and the Cancer Prevention Research Institute of Texas (CPRIT). She is on the External Advisory Boards of the Yale, Case, and MGH Comprehensive Cancer Centers.