Pathology & Lab Medicine
Cancer Cell Biology
Area of interest
The overall goal of my research is to understand the signaling mechanisms whereby integrin-dependent signals regulate growth and development in the cardiovascular system. Activation of the integrin families of transmembrane, cell surface receptors is mediated by contact with extracellular matrix (ECM) components such as fibronectin and collagen and leads to the formation of focal adhesion structures. Focal adhesions contain not only cytoskeletal components that physically tether the integrin cytoplasmic tail to the actin cytoskeleton, but also a number of signaling molecules that are activated in an adhesion-dependent fashion. Recruitment of the protein tyrosine kinase, Focal Adhesion Kinase (F AK), to the integrin cytoplasmic tail appears to be central to focal adhesion formation and subsequent downstream signaling. Studies from our laboratory and others have shown that matrix interactions are important for cell growth and survival and that activation of F AK is required for growth factor-stimulated signaling. However, increased F AK expression has been correlated with metastatic potential in certain human cancer cells, indicating that unregulated F AK activity my lead to uncontrolled cell growth.
Our future directions involve the use of biochemical and genetic approaches to identify mechanisms by which F AK influences myocardial growth and development. In collaboration with Dr. Seth Grant (University of Edinburgh) we plan to develop cardiac-specific F AK null mice. We will study the growth and development of the heart in these animals using both physical and histological methods. In addition, using cultured F AK null cardiomyocytes, we will identify the point of convergence between integrin- and growth factor- signaling. The studies outlined above were previously supported by an American Cancer Society IRG seed grant and an American Heart Affiliate Grant-In-Aid and are currently funded by an American Heart Scientist Development Grant.
Awards and Honors
Active, American Heart Association National Scientist Development Grant, “The Role of Focal Adhesion Kinase Signaling in Cardiac Hypertrophy” (1/1/00-12/31/04; $65,000/yr $260,000 total)
Midwest Pharmacological Sciences Training Program Thomas H. Baum Award for Outstanding Poster Presentation (1991)
University of Michigan Student Medical Research Grant (summer 1988)
Member, Sigma Xi Scientific Honor Society (1992-present)