Peter Rotwein, MD
Growth factors, signal transduction pathways, hormone action, gene regulation, biochemistry and molecular biology of somatic growth and tissue repair and regeneration.
Peptide growth factors regulate cell division, intermediary metabolism, and differentiation by binding to and activating specific cell-surface receptors, and play essential roles in the growth and development of organisms as diverse as flies, worms, frogs, mice, and humans. Our laboratory studies the regulation and actions of the insulin-like growth factors (IGFs), peptides critical for normal embryonic and post-natal growth in mammals and other vertebrate species, and important for controlling aging and senescence. One major research direction focuses on the signaling mechanisms of IGF-mediated muscle and bone differentiation. These studies make use of genetic complementation of cell lines engineered to lack different components of the IGF system, and our ability to knockdown and replace key signaling molecules. Goals are to define the target genes and proteins critical to both stimulation of differentiation and promotion of tissue regeneration, which distinguish the actions of the IGFs from those of other peptide growth factors. Our other major research area focuses on control of IGF gene expression. Growth hormone, another key regulator of somatic growth, activates IGF-I gene transcription via the Jak - Stat pathway. We have established that Stat5b is the key transcriptional intermediate in this process, but the biochemical mechanisms have not been defined. Goals are to use a combination of bioinformatics, and molecular genetic and molecular biological approaches to dissect this pathway. As growth hormone and IGF-I have been used both therapeutically and illicitly to build body mass, our observations will have both scientific and biomedical implications.