Faculty : Departmental- Primary

Pedro Salas, M.D., Ph.D.

Many eukaryotic cells are polarized (asymmetric). Among them, epithelial cells form barriers that separate the external environment from the internal milieu. The polarization of their plasma membrane into apical (luminal) or basolateral domains enable the tissue to absorb or secrete. Mutations of polarized epithelial proteins result in common genetic diseases such as cystic fibrosis or polycystic kidney disease. My laboratory is interested in the molecular mechanisms involved in the acquisition and maintenance of polarity, which can be categorized in three general groups: membrane traffic, organization of the cytoskeleton and polarized signaling. In addition, submembrane scaffolds ultimately attached to the cytoskeleton recruit cytosolic proteins that become polarized and serve, in turn, to support signaling localized to the apical or basolateral domains.

We are currently engaged in two different projects:

  • We are studying the cross-talk of the polarity complex (aPKC-Par6-Par3) with innate immunity pathways such as NF-kB.
  • We are interested in the role of polarized signaling in intestinal epithelia in the effects downstream of myosin 5b loss-of-function mutations (microvillus inclusion disease). Funded by the National Institute of Diabetes, Digestive and Kidney diseases.

Select Publications

  • 2016 Forteza R, Figueroa Y, Mashukova A, Dulam V, Salas PJ. 2016. Conditional knockout of polarity complex (atypical) PKCι reveals an anti-inflammatory function mediated by NF-kB. Mol Biol Cell. 2016 May 25. pii: mbc.E16-02-0086. [Epub ahead of print] PubMed PMID: 27226486
  • 2015 Mashukova A., Forteza R., Salas P.J. 2015. Functional analysis of keratin-associated proteins in intestinal epithelia: Heat-shock protein chaperoning and kinase rescue. Meth. Enzymol. 569:139-154. doi:10.1016/bs.mie.2015.08.019.
  • 2014 Mashukova A., Kozhekbaeva Z., Forteza R., Dulam V., Figueroa Y, Warren R, and Salas P.J. 2014. BAG-1M regulates keratin-associated Hsp70 chaperoning of aPKC in intestinal cells under inflammatory signaling. J. Cell Sci 15;127(Pt 16):3568-77. doi: 10.1242/jcs.151084.
  • 2014 Kravtsov D., Mashukova A., Forteza R., Ameen N., Salas P.J. 2014. Myosin 5b loss of function leads to defects in polarized signaling: Implication for Microvillus Inclusion Disease pathogenesis and treatment. Am. J. Physiol. – GI and Liver Physiology 307(10):G992-G1001. doi: 10.1152.
  • 2013 Forteza R., Wald F.A., Mashukova A., Kozhekbaeva Z., and Salas P.J. 2013. Par-complex aPKC and Par3 cross-talk with innate immunity NF-kB pathway in epithelial cells. Biol. Open, 2(11):1264-9. PMC3828774.
  • 2012 Anastasia Mashukova; Radia Forteza; Flavia A. Wald; Pedro J. Salas PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia Molecular Biology of the Cell. 2012;23(9):1664-1674.
  • 2011 Anastasia Mashukova; Flavia A. Wald; Pedro J. Salas Tumor necrosis factor alpha and inflammation disrupt the polarity complex in intestinal epithelial cells by a posttranslational mechanism Molecular and Cellular Biology. 2011;31(4):756-765.
  • 2011 Flavia A. Wald; Radia Forteza; Runa Diwadkar-Watkins; Anastasia Mashukova; Robert Duncan; Maria T. Abreu; Pedro J. Salas Aberrant expression of the polarity complex atypical PKC and non-muscle myosin IIA in active and inactive inflammatory bowel disease Virchows Archiv. 2011;459(3):331-338.
  • 2009 Anastasia Mashukova; Andrea S. Oriolo; Flavia A. Wald; M. Llanos Casanova; Cornelia Kröger; Thomas M. Magin; M. Bishr Omary; Pedro J.I. Salas Rescue of atypical protein kinase C in epithelia by the cytoskeleton and Hsp70 family chaperones Journal of Cell Science. 2009;122(14):2491-2503.
  • 2008 Flavia A. Wald; Andrea S. Oriolo; Anastasia Mashukova; Nevis L. Fregien; Amber H. Langshaw; Pedro J.I. Salas Atypical protein kinase C (iota) activates ezrin in the apical domain of intestinal epithelial cells Journal of Cell Science. 2008;121(5):644-654.
  • 2007 Andrea S. Oriolo; Flavia A. Wald; Gisella Canessa; Pedro J. I. Salas GCP6 binds to intermediate filaments: A novel function of keratins in the organization of microtubules in epithelial cells Molecular Biology of the Cell. 2007;18(3):781-794.
  • 2007 Andrea S. Oriolo; Flavia A. Wald; Victoria P. Ramsauer; Pedro J.I. Salas Intermediate filaments: A role in epithelial polarity Experimental Cell Research. 2007;313(10):2255-2264.

View published research articles by Dr. Salas in the National Center for Biotechnology Information.