Graduate Studies Faculty
Peter Scott. Rotwein, M.D.
Programs:Biochemistry & Molecular Biology
Neuroscience Graduate Program
Program in Molecular & Cellular Biosciences
Research Interests:growth factors, growth hormone, insulin-like growth factors, muscle development, muscle differentiation, signal transduction pathways, gene regulation, gene transcription, chromatin organization, osteoblast biology, bone development, Stats, protein biosynthesis » PubMed Listing
Preceptor RotationsAcademic Term Available Winter 2014 Yes Spring 2014 Yes
Faculty MentorshipDr. Rotwein is available as a mentor for 2013-2014.
After receiving his B.A. from Yale University in 1971, Peter Rotwein earned his M.D. from Albert Einstein College of Medicine in 1975. Following residency training in internal medicine at Albert Einstein, and clinical training in endocrinology and metabolism at Einstein and Washington University School of Medicine, Rotwein did postdoctoral work in molecular biology at Washington University. He joined the faculty at Washington University School of Medicine as Assistant Professor in 1983, and became Professor of Biochemistry & Molecular Biophysics and Medicine in 1993. In 1997 he joined OHSU as Director of the Molecular Medicine Division. Since 2004 he has been Chair of the Department of Biochemistry and Molecular Biology.
SUMMARY OF CURRENT RESEARCH
My laboratory studies how hormone and growth factor mediated signaling networks influence genetically determined transcriptional programs to control mesenchymal stem cell differentiation and function. We investigate the specific biological actions of Akts, intracellular serine-threonine protein kinases that are involved in cancer progression and metastasis, and examine regulation of the growth hormone (GH) – insulin-like growth factor-I (IGF-I) signaling axis, another pathway with broad physiological relevance that also has been linked with increased risk for selected diseases. We are particularly interested in the mechanisms controlling the dynamic assembly and disassembly of multi-protein complexes at different stages of signal propagation. Our current focus is on two distinct problems within this broad topic. First, we have established that the two closely related signaling enzymes, Akt1 and Akt2, play distinct and non-overlapping roles in muscle and bone development. Actions of Akt1 are necessary at the earliest commitment stages of myoblast differentiation, but Akt2 is dispensable. In contrast, Akt2 is a critical mediator of the early steps in osteoblast differentiation, while Akt1 is a negative regulator of osteogenic differentiation, but is a key mediator in osteoblast - osteoclast coupling, which determines the rate and extent of bone remodeling. We would like to define the unique cell-type specific dynamic signaling complexes that distinguish the biological actions of Akt1 and Akt2 in muscle and bone cell precursors, and plan to use a combination of mouse genetics, cell-based studies, and systems biological approaches to address these issues, which have translational reverberations with regard to musculoskeletal regeneration and repair. Second, in the process of elucidating the molecular mechanisms of action of GH, we have learned that the latent transcription factor, Stat5b, is a critical component of GH-regulated IGF-I gene expression. We would like to understand at a biochemical level of resolution the dynamics of activation of Stat5b in the cell, particularly how it moves from being a monomeric inactive protein in the cytoplasm, to becoming activated by tyrosine phosphorylation at the GH receptor in the cell membrane, to forming a homodimer, being translocated to the nucleus, and interacting with other transcriptional regulatory proteins at specific DNA binding sites on chromatin near target genes. Related pertinent questions will address the differences in functions of the four GH-regulated Stats, Stat1, 3, 5a, and 5b, and we would like to learn the unique features of each of these closely related molecules as mediators of specific facets of GH action. Our studies relate broadly to both normal and abnormal physiology, and have potential translational impact in human disease by providing insights into how to influence both normal and aberrant signaling pathways.