The David H. Koch Institute for Integrative Cancer Research at MITThe David H. Koch Institute for Integrative Cancer Research at MIT

Massachusetts Institute of Technology

National Cancer Institute Cancer Center

Science + Engineering... Conquering Cancer Together

Matthew Vander Heiden, MD, PhD

Matt Vander Heiden

Associate Professor of Biology

Associate Director, Koch Institute for Integrative Cancer Research

Member, MIT Center for Precision Cancer Medicine

Member, Ludwig Center for Molecular Oncology

Member, Broad Institute of Harvard and MIT

 

KI Research Areas of Focus:
Personalized Medicine,
Metastasis

"One of the first differences described between cancer cells and normal cells was a difference in metabolism. Using a combination of biochemistry, cell biology and mouse models, our laboratory studies how metabolism is regulated to influence different stages of tumor biology with a major goal to find novel approaches to treat cancer in the clinic."

Mathew Vander Heiden is an Associate Professor in the Department of Biology, an Associate Director of the Koch Institute at MIT, and a member of the Broad Institute. He is a practicing oncologist and instructor in medicine at Dana-Farber Cancer Institute / Harvard Medical School. He earned his doctoral and medical degrees from the University of Chicago, where he worked in the laboratory of Craig Thompson. Vander Heiden then completed a residency in internal medicine at Boston’s Brigham & Women’s Hospital and a hematology-oncology fellowship at Dana-Farber Cancer Institute / Massachusetts General Hospital. He was a postdoctoral fellow in the laboratory of Lewis Cantley at Harvard Medical School, where he was supported by a Mel Karmazin Fellowship from the Damon Runyon Cancer Research Foundation. In 2010, Vander Heiden joined the MIT faculty. His work has been recognized by many awards including the Burroughs Wellcome Fund Career Award for Medical Sciences, the AACR Gertrude B. Elion Award, the HHMI Faculty Scholar Award, and an NCI Outstanding Investigator Award. Dr. Vander Heiden serves on the scientific advisory board of Yale Cancer Center, Agios Pharmaceuticals, Aeglea Biotherapeutics, iTeos Therapeutics, Evelo Therapeutics, CyteGen, and Auron Therapeutics, of which he is also an academic founder. He is part of the investment advisory board for DROIA Venture Fund.

Research Summary

Cancer cells have metabolic requirements that differ from most normal, non-proliferating cells. To proliferate, cancer cells must transform available nutrients into the varied array of macromolecules that are needed to build a new cell. Each cancer type is unique and will have a metabolic phenotype that depends on tissue type, genetic factors, and local environment. How specific cancers integrate these factors and rewire their metabolism to support cancer progression is a major unanswered question.

The long-term goal of the Vander Heiden lab is to understand how mammalian cell metabolism is adapted to support cancer initiation and progression. The metabolic phenotypes of proliferating cells are typically interpreted with an emphasis on either energy generation or the crosstalk between signaling events and cell metabolism. This has led many to focus on how cancer genetics influence metabolic pathway use. The Vander Heiden lab takes a different approach that identifies limiting metabolic processes, considers how these are constrained by the extracellular environment, and defines how metabolic limitations are overcome within a physiological tissue context.

Using mass spectrometry to trace nutrient fate in cancer models, the Vander Heiden lab generates hypotheses for how different cancers use metabolism to support cell proliferation and tumor growth. They test these hypotheses using a variety of biochemical and genetic approaches to define how nutrient availability, metabolic pathway regulation, and tissue context constrain how cells use available materials to proliferate. The current interests of the laboratory include: 1) identifying which metabolic processes create bottlenecks for cell proliferation; 2) determining how metabolism is different in different cancers, examining in detail the influence of tissue type, tumor genetics, and tumor microenvironment; and 3) understanding how diet and whole body metabolism influence cell metabolism in tissues to modify cancer and other disease phenotypes. Through this work, they aim to advance understanding of metabolic pathway biochemistry and its relationship to cancer and mammalian physiology. Together, these studies will broaden our understanding of cancer cell metabolism will also identify approaches to target metabolism for cancer therapy.

Learn more about the Vander Heiden lab and their efforts to better understand cancer cell metabolism and how small molecules might be used to activate enzymes and restore the normal state of cells by watching this video: "Inside the Lab: Matthew Vander Heiden, M.D., Ph.D."

The Vander Heiden lab's work is profiled as part of the current interactive exhibits in the Koch Institute Public Galleries.  Watch a web version of the story here.

Selected Publications

Lau AN, Li Z, Danai LV, Westermark AM, Darnell AM, Ferreira R, Gocheva V, Sivanand S, Lien EC, Sapp KM, Mayers JR, Biffi G, Chin CR, Davidson SM, Tuveson DA, Jacks T, Matheson NJ, Yilmaz O, Vander Heiden MG. Dissecting cell type-specific metabolism in pancreatic ductal adenocarcinoma. Elife. 2020 Jul 10;9:e56782.

Luengo A, Abbott KL, Davidson SM, Hosios AM, Faubert B, Chan SH, Freinkman E, Zacharias LG, Mathews TP, Clish CB, Deberardinis RJ, Lewis CA, Vander Heiden MG. Reactive metabolite production is a targetable liability of glycolytic metabolism in lung cancer. Nat Commun. 2019 Dec 6;10(1):5604.

Diehl FF, Lewis CA, Fiske BP, Vander Heiden MG. Cellular redox state constrains serine synthesis and nucleotide production to impact cell proliferation. Nat Metab. 2019 Sept 16; 1(861-867).

Sullivan MR, Mattaini KR, Dennstedt EA, Nguyen AA, Sivanand S, Reilly MF, Meeth K, Muir A, Darnell AM, Bosenberg MW, Lewis CA, Vander Heiden M. Increased Serine Synthesis Provides an Advantage for Tumors Arising in Tissues Where Serine Levels Are Limiting. Cell Metab. 2019 Jun 4;29(6):1410-1421.e4.

Sullivan MR, Danai LV, Lewis CA, Chan SH, Gui DY, Kunchok T, Dennstedt EA, Vander Heiden MG, Muir A. Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability. Elife. 2019 Apr 16;8. pii: e44235.

Danai LV, Babic A, Rosenthal MH, Dennstedt EA, Muir A, Lien EC, Mayers JR, Tai K, Lau AN, Jones-Sali P, Prado CM, Petersen GM, Takahashi N, Sugimoto M, Yeh JJ, Lopez N, Bardeesy N, Fernandez-Del Castillo C, Liss AS, Koong AC, Bui J, Yuan C, Welch MW, Brais LK, Kulke MH, Dennis C, Clish CB, Wolpin BM, Vander Heiden MG. Altered exocrine function can drive adipose wasting in early pancreatic cancer. Nature. 2018 Jun;558(7711):600-604.

Muir A, Danai LV, Gui DY, Waingarten CY, Lewis CA, Vander Heiden MG. Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition. Elife. 2017 Aug 15;6. pii: e27713.

Mayers JR, Torrence ME, Danai LV, Papagiannakopoulos T, Davidson SM, Bauer MR, Lau AN, Ji BW, Dixit PD, Hosios AM, Muir A, Chin CR, Freinkman E, Jacks T, Wolpin BM, Vitkup D, Vander Heiden MG. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. Science. 2016 Sep 9;353(6304):1161-5.

Davidson SM, Papagiannakopoulos T, Olenchock BA, Luengo A, Heyman JE, Keibler MA, Bauer MR, O’Brien JP, Pierce KA, Gui DY, Wasylenko TM, Mott BT, Chin CR, Stephanopolous G, Jacks T, Clish CB, Vander Heiden MG. Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer. Cell Metab. 2016 Mar 8;23(3):517-28.

Sullivan LB, Gui DY Hosios AM, Bush LN, Freinkman E, Vander Heiden MG. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell. 2015 Jul 30;162(3):552-63.

Search PubMed for Vander Heiden lab publications

Contact Information

Matthew Vander Heiden

room 76-561
phone (617) 715-4471
email mvh@mit.edu

Vander Heiden Lab

phone (617) 715-4523
fax (617) 253-3189
website

Administrative Assistant:

Peter Jansen
phone (617) 252-1163
email pejansen@mit.edu