Upcoming Talk by Dr. Robert Krauss

Robert Krauss, P.h.D. will be speaking as a PCB invitee for the Knight Cancer Institute Seminar Series on November 30, 2010 in the OHSU Main Hospital 8th Floor Conference Room (8B60).  Dr. Krauss, Professor of Developmental and Regenerative Biology at Mount Sinai School of Medicine, is a developmental biologist with interests in the Sonic Hedgehog pathway.  His work is relevant to cancer as well as neurology and neuroscience. Dr. Krauss will be presenting a seminar titled: “Modeling the Holoprosencephaly Spectrum in the Mouse: Regulation of Sonic Hedgehog Signaling by Co-receptors.”

  

more about Dr. Krauss' 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/p38a/b complexes to the intracellular region of Cdo and thereby links extracellular cell-cell contact to activation of a pathway (p38a/b) 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.

 

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 have used these mice to develop additional models of HPE that include gene-environment interactions and recapitulate the major features of human HPE.