Michael Centrella PhD

Professor of Surgery (Plastic)

Departments & Organizations

Biography

My lab was the first to identify and isolate TGF-beta, IGF-I, PDGF-AA, and a novel estrogen receptor ligand from bone and bone forming osteoblasts, and more recently, a component of the low molecular mass soluble RNA pool that suppresses protein synthesis initiation in eukaryotes. We cloned and produced the first detailed nest of TGF-beta receptor gene promoter fragments, and identified complex biochemical and molecular control through distinct cis- and trans- acting elements in these and several other promoters that drive tissue, hormone, and growth factor restricted gene expression. We demonstrated that variations like these altered the expression of TGF-beta receptor proteins and, in so doing, effectively changed their relative proportions on the cell surface. This occurred in parallel with downstream differences in TGF-beta signaling in, among other cell types, osteoblasts, fibroblasts, cardiocytes, renal epithelial cells, and vascular endothelial cells. During the last three decades, we also characterized interactions among many other bone growth factors, hormones, and stress-induced events in bone organ and cell cultures, and showed that they culminated in downstream changes in replication, gene expression, protein synthesis, and other molecular and biochemical parameters well associated with tissue growth. My efforts continue to benefit greatly from the experience and shared interests of long term co-investigators at Yale and elsewhere. We are members of the Yale Core Center for Musculoskeletal Disorders and Diabetes and Endocrinology Research Center.