Leonard Anderson's Research Laboratory

Dr. Anderson's research laboratory is focused on cardiovascular genomics. In particular, the modulation of the cellular transcriptome during early vascular smooth muscle cell (VSMC) fate determination from pluripotent stem cells in cell-based and murine models of differentiation and development.

GENOMIC ANALYSIS OF VASCULAR SMOOTH MUSCLE CELL DIFFERENTIATION

Vascular diseases involving hyperproliferation of VSMCs, such as atherosclerosis, is one of the major causes of mortality in the U.S. and one of the leading causes of mortality among African Americans. VSMCs play a critical role in early vasculogenesis and blood vessel maintenance. The requirement for VSMC replenishment after vessel injury by putative stem cell progenitors suggest unique changes in the cellular transcriptome when compared to other cell lineages such as neurons, skeletal muscle, and cardiomyocytes. Our lab is currently interested in defining the process by which pluripotent stem cells become VSMCs at the transcriptional and, hence, signal transduction level by utilizing various innovative genomics technologies (i.e. Agilent OligoArrays, Affymetrix GeneChips, and protein arrays) to identify novel genes and proteins that play a crucial role in early VSMC fate determination. We are functionally characterizing these genes in pluripotent mouse embryonal carcinoma stem cells (P19) and various clonal derivatives by utilizing either 'gain of-' or 'loss of-' function methodologies to alter expression levels of identified genes. These functional genomics studies will provide insight into the mechanism(s) by which specific genes are involved in early cell lineage determination within the vasculature. Although the therapeutic potential of ES cell-derived ex vivo therapy has been demonstrated in mouse models of atherosclerosis and restenosis after balloon angioplasty, the outcome of these studies suggest further understanding of the basic molecular mechanisms involved in this process is required. The outcome of our genomic studies will allow us to gain insight into these early signaling events and potentially generate modified ES cells with a predetermined VSMC, and thus, greater therapeutic efficacy in vivo.