David L. Geenen, Ph.D.
Office: 312-355-1623
FAX: (312) 996-5062
Research Associate Professor
Section of Cardiology
Department of Medicine
University of Illinois at Chicago
Graduate School: University of Michigan
Postdoctoral Fellowship: Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY
Areas of Expertise: Cardiac Physiology, Cardiac Muscle Intracellular Signaling
Research Interests: Cardiac hypertrophy is an adaptive process that is mediated by chronic extracellular stimuli through myocyte membrane receptors. The mechanism by which the internal structure of the muscle cell senses these mechanical and hormonal changes in its environment and translates them into specific patterns of gene expression is a complex process. It has been proposed that one mechanism by which mechanical signals are transduced across the plasma membrane into the cytoplasm is through the heterodimeric transmembrane receptors called integrins that are tethered to the cytoskeleton and form receptor-ligand complexes with the extracellular matrix proteins (see illustration). Once the integrins engage the extracellular matrix, they cluster to form focal adhesions that promote cell spreading and growth. Key signaling proteins of the focal adhesions and cytoskeleton interact with and phosphorylate tyrosine and serine/threonine residues, and in some instances may act as anchoring proteins or chaperones to induce specific intracellular localization. Two proteins within this family are the recently cloned receptors for activated C kinase (RACK1 and RACK2). My laboratory is interested in these receptors because they bind the activated form of protein kinase C (PKC), a ubiquitous enzyme that is implicated in the phosphorylation of a number of intracellular proteins including those in the cardiac myocyte. RACK1 also binds, among other proteins, the cytoplasmic domain of integrin b1, and the non-receptor tyrosine kinase, c-Src. Both this transmembrane receptor and tyrosine kinase have been implicated in the signaling pathways that activate cell proliferation and gene expression.
