• Researcher Profile

    Matthew Vander Heiden, MD, PhD

     
    Matthew Vander Heiden, MD, PhD
     
    Instructor in Medicine, Harvard Medical School; Assistant Professor, MIT

    Center/Program

    Genitourinary Oncology

    Office phone: 617-632-5456
    Fax: 617-632-2165

    Preferred contact method: appointment phone

    View Physician Profile
     
     

    Interests

    Cancer research, Cancer cell metabolism

    Area of Research

    Basic science, cancer cell metabolism, target metabolism in cancer

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    D1230
    Boston, MA 02215

    Recent Awards

    • Burroughs Wellcome Fund Career Award for Medical Scientists, 2009
    • Mel Karmazin Fellowship, Damon Runyon Cancer Research Foundation, 2006

    Research

    Basic science, cancer cell metabolism, target metabolism in cancer

    Recently, there has been a resurgent interest among the scientific community to understand cancer cell metabolism. My research has focused on understanding how cancer cells convert nutrients into the cellular components needed to proliferate.

    We have made inroads into this basic science question by studying the form of a protein involved in glucose metabolism that is present at high levels in all cancer cells. This protein contributes to the form of metabolism carried out by tumor cells and is different from the enzyme found in many normal tissues because it can communicate with cell growth signal. These growth signals turn off activity of the enzyme.

    This finding demonstrated a heretofore unappreciated biochemical link between cell growth signals and regulation of a metabolic pathway.

    My laboratory's current efforts have been to test the hypothesis that cell growth signals reprogram metabolism to support the distinct energetic needs of proliferating cells.

    Unlike normal cells, which rely heavily on ATP to support housekeeping functions, proliferating cells have the additional requirement of duplicating mass. This large synthesis requirement for lipids, amino acids, and nucleotides requires an excess of carbon and reducing equivalents. Metabolic processes in proliferating cells must be reprogrammed to balance ATP production with the production of building blocks required for growth.

    Efforts to understand how metabolism is reprogrammed to facilitate accumulation of biomass have furthered our understanding of glucose metabolism in proliferating cells. In addition, we are using this knowledge to explore novel therapeutic approaches to target tumor cell metabolism for therapy.

    Select Publications

    • Vander Heiden, M.G., Christofk, H.R., Schuman, E., Subtelny, A.O., Sharfi, H., Harlow, E.E., Xian, J., and Cantley, L.C. Identification of small molecule inhibitors of pyruvate kinase M2. Biochem. Pharm. In press
    • Boxer, M.B., Jiang, J.-K., Vander Heiden, M.G., Shen, M., Skournbourdis, A.P., Southall, N., Veith, H., Leister, W., Austin, C.P., Park, H.W., Inglese, J., Cantley, L.C., Auld, D.S., and Thomas, C.J. Evaluation of Substituted N,N-diarylsulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase. J.Med.Chem. In press
    • Dang, L., White, D.W., Gross, S., Bennett, B.D., Bittinger, M.A., Driggers, E.M., Fantin, V.R., Jang, H.G., Jin, S., Keenan, M.C., Marks, K.M., Prins, R.M., Ward, P.S., Yen, K.E., Liau, L.M., Rabinowitz, J.D., Cantley, L.C., Thompson, C.B., Vander Heiden, M.G., and Su, S.M. Cancer-associated IDH-1 mutations produce 2-hydroxyglutarate.Nature. In press. (2009)
    • Hitosugi, T., Kang, S., Vander Heiden, M.G., Chung, T.W., Elf, S., Lythgoe, K., Dong, S., Lonial, S., Wang, X., Chen, G.Z., Xie, J., Gu, T.L., Polakiewicz, R.D., Roesel, J.L., Boggon, T.J., Khuri, F., Gilliland, D.G., Cantley,. L.C., Kaufman, J., and Chen, J. (2009) Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal. 2:ra73 (2009).
    • Locasale, J.W., Cantley, L.C., Vander Heiden, M.G. (2009) Cancers insatiable appetite. Nature Biotech., 27: 916-917.
    • Vander Heiden, M.G., Cantley, L.C., Thompson, C.B. (2009) Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 324: 1029-1033.
    • Christofk, H.R., Vander Heiden, M.G., Harris, M.H., Ramanathan, A., Gerszten, R.E., Wei, R., Fleming, M.D., Schreiber, S.L., Cantley, L.C. (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452: 230-233.
    • Christofk, H.R., Vander Heiden, M.G., Wu, N., Asara, J.M., Cantley, L.C. (2008) Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452: 181-186.
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