Graduate Studies Faculty

Preceptor Rotations

Faculty Mentorship

Profile

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.

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 cancers. 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 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. 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 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.