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Robert Krauss

  • PROFESSOR Developmental and Regenerative Biology
  • PROFESSOR Oncological Sciences
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Education

  • Ph.D., University of North Carolina

  • Postdoc, Columbia University

Biography

Research

 
The Krauss lab is interested in regulation of cell adhesion and signal transduction pathways during development and how such processes may go awry in disease. We have focused much of our effort on a small group of complex and multifunctional receptor-like proteins of the Ig superfamily. Cdo and Boc have Ig and FnIII repeats in their ectodomains and long, divergent cytoplasmic tails. Cdo and Boc function as components of cell surface protein complexes to influence signaling by cadherins, netrins and Sonic hedgehog (Shh). Cdo promotes skeletal myogenesis in vivo and in vitro. Cdo binds in a cis manner (in the plane of the same cell membrane) to the cell-cell adhesion molecule N-cadherin. N-cadherin ligation during myoblast differentiation stimulates binding of Bnip-2/Cdc42 and JLP/p38α/β complexes to the intracellular region of Cdo and thereby links extracellular cell-cell contact to activation of a pathway (p38α/β) that controls a cell-type specific transcriptional program. In addition, Cdo binds in a cis manner to the netrin and RGM receptor, neogenin to influence netrin-mediated signaling during myogenesis. We are currently studying the signaling pathways that are activated downstream of these adhesion-dependent complexes to promote myoblast differentiation and fusion.

Cdo and Boc also function as both components and targets of the Hedgehog signaling pathway and feedback network. Cdo and Boc bind directly to Sonic hedgehog (Shh) and promote Shh signaling. Mice lacking Cdo or Boc display tissue-specific loss-of-Shh function phenotypes. Cdo-null animals display holoprosencephaly (HPE). HPE is one of the most common human birth defects and is associated with haploinsufficiency for genes encoding Shh pathway components. Clinical expression of HPE is extremely variable, but it is rarely associated with defects in other Shh-dependent structures, such as the limbs. Mice lacking Cdo display HPE with strain-specific severity and without limb defects, modeling human HPE and implicating silent modifier genes as a cause of variability. Boc-null mice are viable, but removal of Boc from Cdo mutant mice worsens the latter’s HPE phenotype. We are working on development of additional mouse models of HPE, including ones that encompass gene-environment interactions. We are also studying Cdo and Boc promote Shh signaling. Recent results have identified Cdo mutations in human HPE; these mutations result in defects in Cdo's ability to associate with other Shh receptors, suggesting that such receptors must interact for ligand-dependent signaling to occur.

For more information, please visit the Krauss Laboratory website.

Publications

Romer AI, Singh J, Rattan S, Krauss RS. Smooth muscle fascicular reorientation is required for esophageal morphogenesis and dependent on Cdo. J. Cell Biol. 2013; 201: 309-323.

Hong M, Krauss RS. Cdon mutation and fetal ethanol exposure synergize to produce midline signaling defects and holoprosencephaly spectrum disorders in mice. PLoS Genet. 2012; 8(10): e1002999.

Bae GU, Domené S, Roessler E, Schachter K, Kang JS, Muenke M, Krauss RS. Mutations in CDON, encoding a hedgehog receptor, result in holoprosencephaly and defective interactions with other hedgehog receptors. Amer. J. Hum. Genet. 2011; 89: 231-240.

Allen BL, Song JY, Izzi L, Althaus IW, Kang JS, Charron F, Krauss RS, McMahon AP. Overlapping roles and collective requirement for the co-receptors Gas1, Cdo and Boc in Shh pathway function. Dev Cell 2011; 20: 775-787.

Zhang W, Hong M, Bae GU, Kang JS, Krauss RS. Boc modifies the holoprosencephaly spectrum of Cdo mutant mice. Dis Model Mech 2011; 4: 368-380.

Lu M, Krauss RS. N-cadherin ligation, but not Sonic hedgehog binding, initiates Cdo-dependent p38α/β MAPK signaling in skeletal myoblasts. Proc. Natl. Acad. Sci. (USA) 2010; 107: 4212-4217.

Bae GU, Yang YJ, Jiang G, Hong M, Lee HJ, Tessier-Lavigne M, Kang JS, Krauss RS. The Ig superfamily member neogenin regulates myofiber size and focal adhesion kinase and extracellular signal-regulated kinase activities in vivo and in vitro. Mol. Biol. Cell 2009; 20: 4920-4931.

Kang JS, Bae GU, Yi MJ, Yang YJ, Oh JE, Takaesu G, Zhou YT, Low BC, Krauss RS. A Cdo/Bnip-2/Cdc42 signaling pathway regulates p38α/β MAPK activity and myogenic differentiation. J. Cell Biol. 2008; 182: 497-507.

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Krauss did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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