• Researcher Profile

    Martin E. Hemler, PhD

     
    Martin E. Hemler, PhD
     
    Professor of Pathology, Harvard Medical School

    Office phone: 617-632-3410
    Fax: 617-632-2662
    Email: martin_hemler@dfci.harvard.edu
    Website: Hemler Lab Website

    Preferred contact method: email
     
     

    Research Department

    Cancer Immunology and Virology

    Area of Research

    Novel adhesion and palmitoylation mechanisms that regulate the tumor microenvironment


    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana 1430
    Boston, MA 02215

    Biography

    Dr. Hemler received his PhD in biological chemistry from the University of Michigan in 1978. After postdoctoral research at DFCI from 1979 to 1984, he received a faculty appointment at DFCI and was promoted to professor in 1994. He is exclusively involved in basic laboratory research, focusing on cell surface molecules that participate in cell adhesion, migration, and invasion.

    Research

    Novel adhesion and palmitoylation mechanisms that regulate the tumor microenvironment

    As tumor cells progress to a cancerous state, they may begin to invade surrounding tissue and metastasize to distant sites. These invasion and metastasis processes are highly dependent on cancer cell surface molecules that participate in cell adhesion. A major focus of our laboratory is on a family of adhesion molecules called integrins. For several years, we have sought to determine mechanisms whereby integrin functions can be rapidly turned on and off. Such information is fundamental to our understanding of how cell adhesion, mediated by members of the integrin family, can control cell movement, growth factor responses, gene induction, and tumor growth and metastasis.


    More recently, we have been studying certain key integrins as they form highly specific complexes with cell surface "adapter" tetraspanin proteins, a family of proteins having four transmembrane domains. Remarkably, these tetraspanin proteins act as transmembrane linker molecules that link integrin extracellular domains with intracellular signaling enzymes (such as protein kinase C and phosphatidylinositol 4-kinase). We hypothesize that disruption of these complexes will dramatically affect tumor cell migration, invasion, and metastasis.


    Recent studies have focused on how certain integrins may be linked to regulation of matrix metalloproteinase (MMP) production, a key process during cell and tissue remodeling and tumor cell metastasis. Most recently, they have generated mutant mice in which the tetraspanin CD151 gene has been deleted to investigate the role of CD151 during tumor progression.


    In addition, we are studying mechanisms whereby cell adhesion and migration are regulated in parallel with the proteolytic degradation of tissue and extracellular matrix proteins that surround tumor cells. We hypothesize that specific cell surface complexes between integrins and molecules that regulate protein degradation are responsible for this coordinated regulation. By various molecular and genetic approaches, we seek to disrupt these complexes.


    General approaches used in our laboratory include a monoclonal antibody technique developed for identifying integrin-associated proteins. This experimental approach continues to open up exciting new research directions. We also make use of an extensive array of previously generated integrin mutants as well as cell migration, videomicroscopy, cell adhesion, phosphatidylinositide kinase, and immunofluorescent microscopy assays. In addition, we are currently breeding knockout mice lacking key tetraspanin proteins and testing these mice in various in vivo tumor models.

    Trainees

    • Sharma, Chandan, PhD
    • Li, Qinglin, Ph.D.
    • Knoblich, Konstantin, Ph.D.
    • Wang, Hong-Xing, Ph.D.
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