Steven R. Post

The goal of our ongoing research is to increase our understanding of the involvement of intracellular signal transduction pathways in cardiovascular disease. Our studies involve two cell systems relevant to cardiovascular function and disease; macrophages and cardiac myocytes. Macrophages play a key role in the development and progression of atherosclerosis and other inflammatory diseases. Our work in macrophages relates to defining the interaction between certain lipoprotein receptors and intracellular signaling cascades. Of particular interest is the class A macrophage scavenger receptor (SR-A) which mediates macrophage adhesion and uptake of modified low density lipoprotein (LDL) and other modified proteins. Our results indicate that SR-A-mediated activation of specific intracellular signals plays a key role in regulating endocytosis, phagocytosis, and cell adhesion. In addition, we have shown that the signaling pathways involved in regulating scavenger receptor-mediated endocytosis differentially regulate other endocytic receptors including the LDL receptor. Our ongoing studies will provide mechanistic details regarding the functional interactions between macrophage scavenger receptors and intracellular signaling pathways. Results of these studies will advance understanding of the pathogenesis of atherosclerosis and may indicate novel therapeutic approaches for the treatment of this prevalent cardiovascular disease.

The second area of research in our lab relates to understanding the signaling pathways involved in regulating the response of cardiac myocytes to hypertrophic stimuli. Initially, cardiac hypertrophy represents a compensatory response to cardiovascular disease or other insults. However, this initial response often progresses to a decompensated stage characterized by a loss in cardiac myocyte function ultimately resulting in cardiac failure. Numerous studies have implicated a role for the monomeric G protein Ras in both the compensated and decompensated stages. Our lab is interested in determining the intracellular factors that regulate Ras signaling in cardiac myocytes. We have identified a protein that interacts with Ras and selectively regulates Ras-mediated activation of kinase cascades. Our current studies will determine the mechanism by which Rlf selectively regulates Ras signaling and the potential role of Rlf in regulating cardiac myocyte hypertrophy in both in vitro and in vivo models.