Photo of Peter Rotwein, MD

Peter Rotwein MD

  • 5034940537
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.

Publications

  • "Separating myoblast differentiation from muscle cell fusion using IGF-I and the p38 MAP kinase inhibitor SB202190." American Journal of Physiology - Cell Physiology  In: , Vol. 309, No. 7, 01.09.2015, p. C491-C500.
  • "Akt signaling dynamics in individual cells." Journal of Cell Science  In: , Vol. 128, No. 14, 2015, p. 2509-2519.
  • "Editorial : Is it time for an evolutionarily based human endocrinology?" Molecular Endocrinology In: , Vol. 29, No. 4, 2015, p. 487-489.
  • "Differential effects of STAT proteins on growth hormone-mediated IGF-I gene expression." American Journal of Physiology - Endocrinology and Metabolism  In: , Vol. 307, No. 9, 01.11.2014, p. E847-E855.
  • "Distinct actions of Akt1 on skeletal architecture and function." PLoS One  In: , Vol. 9, No. 3, e93040, 24.03.2014.
  • "Editorial : the fall of mechanogrowth factor?" Molecular endocrinology (Baltimore, Md.)  In: , Vol. 28, No. 2, 01.02.2014, p. 155-156.
  • "In Memoriam : William H. Daughaday, MD (1918-2013)." Endocrine Reviews  In: , Vol. 34, No. 6, 01.12.2013, p. 764-765.
  • "In memoriam : William H. Daughaday, MD, 1918-2013." The Journal of clinical endocrinology and metabolism  In: , Vol. 98, No. 11, 11.2013, p. 4217-4218.
  • "In memoriam : William H. Daughaday, MD, 1918-2013." Endocrinology  In: , Vol. 154, No. 11, 11.2013, p. 3953-3954.
  • "In memoriam : William H. Daughaday, MD, 1918-2013." Molecular endocrinology (Baltimore, Md.)  In: , Vol. 27, No. 11, 11.2013, p. 1793-1794.
  • "Proteomic analysis and molecular modelling characterize the iron-regulatory protein haemojuvelin/repulsive guidance molecule c." Biochemical Journal  In: , Vol. 452, No. 1, 15.05.2013, p. 87-95.
  • "Live cell imaging reveals marked variability in myoblast proliferation and fate." Skeletal Muscle  In: , Vol. 3, No. 1, 10, 02.05.2013.
  • "William H. Daughaday and the foundations of modern research into growth hormone and the insulin-like growth factors." Pediatric endocrinology reviews : PER  In: , Vol. 10, No. 3, 03.2013, p. 280-283.
  • "Severe growth deficiency is associated with STAT5b mutations that disrupt protein folding and activity." Molecular Endocrinology  In: , Vol. 27, No. 1, 2013, p. 150-161.
  • "Defining Akt actions in muscle differentiation." American Journal of Physiology - Cell Physiology  In: , Vol. 303, No. 12, 15.12.2012.
  • "Congenic mice provide in vivo evidence for a genetic locus that modulates intrinsic transforming growth factor β1-mediated signaling and bone acquisition." Journal of Bone and Mineral Research In: , Vol. 27, No. 6, 06.2012, p. 1345-1356.
  • "Mapping the growth hormone-Stat5b-IGF-I transcriptional circuit." Trends in Endocrinology and Metabolism  In: , Vol. 23, No. 4, 04.2012, p. 186-192.
  • "Defining the disulfide bonds of insulin-like growth factor-binding protein-5 by tandem mass spectrometry with electron transfer dissociation and collision-induced dissociation." Journal of Biological Chemistry  In: , Vol. 287, No. 2, 06.01.2012, p. 1510-1519.
  • "Selective signaling by Akt1 controls osteoblast differentiation and osteoblast-mediated osteoclast development." Molecular and Cellular Biology  In: , Vol. 32, No. 2, 01.2012, p. 490-500.
  • "Biochemical Characterization of Diverse Stat5b-Binding Enhancers That Mediate Growth Hormone-Activated Insulin-Like Growth Factor-I Gene Transcription." PLoS One  In: , Vol. 7, No. 11, e50278, 2012.
  • "TGF-β inhibits muscle differentiation by blocking autocrine signaling pathways initiated by IGF-II." Molecular Endocrinology  In: , Vol. 25, No. 1, 01.2011, p. 128-137.
  • "Local insulin-like growth factor i expression is essential for Purkinje neuron survival at birth." Cell Death and Differentiation In: , Vol. 18, No. 1, 01.2011, p. 48-59.
  • "Long range interactions regulate Igf2 gene transcription during skeletal muscle differentiation." Journal of Biological Chemistry  In: , Vol. 285, No. 50, 10.12.2010, p. 38969-38977.
  • "Conserved proximal promoter elements control repulsive guidance molecule c/hemojuvelin (Hfe2) gene transcription in skeletal muscle." Genomics  In: , Vol. 96, No. 6, 12.2010, p. 342-351.
  • "Defining the epigenetic actions of growth hormone : Acute chromatin changes accompany GH-activated gene transcription." Molecular Endocrinology  In: , Vol. 24, No. 10, 10.2010, p. 2038-2049.
  • "Dispersed chromosomal Stat5b-binding elements mediate growth hormone-activated insulin-like growth factor-I gene transcription." Journal of Biological Chemistry  In: , Vol. 285, No. 23, 04.06.2010, p. 17636-17647.
  • "Distinct alterations in chromatin organization of the two IGF-I promoters precede growth hormone-induced activation of IGF-I gene transcription." Molecular Endocrinology  In: , Vol. 24, No. 4, 04.2010, p. 779-789.
  • "Gene regulation by growth hormone." Pediatric Nephrology In: , Vol. 25, No. 4, 04.2010, p. 651-658.
  • "Selective signaling by Akt2 promotes bone morphogenetic protein 2-mediated osteoblast differentiation." Molecular and Cellular Biology  In: , Vol. 30, No. 4, 02.2010, p. 1018-1027.
  • "Molecular biology, genetics and biochemistry of the repulsive guidance molecule family." Biochemical Journal  In: , Vol. 422, No. 3, 15.09.2009, p. 393-403.

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