Keith Mostov, MD, PhD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Keith Mostov, MD, PhD

Professor, Departments of Anatomy and Biochemistry/Biophysics, UCSF

keith.mostov@ucsf.edu

Phone: (415) 476-6048 (voice)
Box 2140, UCSF
San Francisco, CA 94143-2140

UCSF Profiles | Mostov Lab Website

Cancer Center Membership

Program Member » Breast Oncology

Research Summary

I discovered and cloned the polymeric immunoglobulin receptor (pIgR) while I was an MD-PhD student with Nobel laureate Günter Blobel and have been a leader in the analysis of the mechanism of how it transcytoses polymeric IgA (pIgA) across epithelial cells ever since. I then moved to the Whitehead Institute as a Whitehead Fellow and PI, where I began R01 AI25144. We expressed the pIgR in MDCK cells and used this as a model to analyze the mechanism of pIgR-pIgA transcytosis, and more generally membrane traffic in polarized epithelial cells. This led to the uncovering of many broad principles in polarized trafficking. We have moved into 3D cultures of epithelial cells in cysts and tubules, which more closely resemble in vivo conditions. We are leaders in how membrane traffic is involved in developing cell polarity in 3D cultures. Most of this work has in common the central role of transcytosis and its regulation. We have trained >50 PhDs and postdoctoral fellows, almost all of whom have academic positions around the world.

Education

University of Chicago, B.A., 1976, Biology
New College, Oxford, Rhodes Scholar, 1976-77, Physiology
Rockefeller University, Ph.D., 1983, Cell Biology
Cornell University Medical College, M.D., 1984, Medicine


Professional Experience

  • 1977-1984
    MD-PhD Program, Rockefeller University and Cornell University (Advisor Günter Blobel)
  • 1984-1988
    Whitehead Fellow and Principal Investigator, Whitehead Institute
  • 1988-1992
    Assistant Professor, University of California, San Francisco
  • 1992-1998
    Associate Professor, University of California, San Francisco
  • 1997-1999
    Vice-Chairman, University of California, San Francisco, Department of Anatomy
  • 1998-present
    Professor, University of California, San Francisco, Departments of Anatomy, and Biochemistry and Biophysics, Cardiovascular Research Inst., Liver Center and Cell Biology Program

Honors & Awards

  • 1976
    Rhodes Scholar
  • 1985
    Charles Hood Foundation Award
  • 1989
    Searle Scholar
  • 1990
    Cancer Research Institute Investigator Award
  • 1991
    Charles E. Culpeper Foundation Scholar in Medical Science
  • 1991
    Edward Mallinckrodt Foundation Medical Scholar
  • 1992
    American Heart Association Established Investigator Award
  • 2002-2012
    NIAID MERIT Award

Selected Publications

  • Mostov, K.E., DeFoor, P., Fleischer, S. and Blobel, G. Co-translational membrane integration of calcium pump protein without signal sequence cleavage. Nature 292:87-88, 1981.
  • Mostov, K.E., Friedlander, M.F. and Blobel, G. The receptor for transepithelial transport of IgA and IgM contains multiple immunoglobulin-like domains. Nature 308:37-43, 1984.
  • Mostov, K.E. and Simister, N. Transcytosis. Cell 43:389-390, 1985.
  • Mostov, K.E. and Deitcher, D.L. Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgA. Cell 47:613-621, 1986.
  • Mostov, K.E., de Bruyn Kops, A. and Deitcher, D.L. Deletion of the cytoplasmic domain of the polymeric immunoglobulin receptor prevents basolateral localization and endocytosis. Cell 47:359-364, 1986.
  • Simister, N.E. and Mostov, K. An Fc receptor structurally related to MHC class I antigens. Nature 337:184-187, 1989.
  • Casanova, J.E., Breitfeld, P.P., Ross, S.A. and Mostov, K.E. Phosphorylation is required for efficient transcytosis of the polymeric immunoglobulin receptor. Science, 248: 742-745, 1990.
  • Casanova, J.E., Apodaca, G., and Mostov, K.E. An autonomous signal for basolateral sorting in the cytoplasmic domain of the polymeric immunoglobulin receptor. Cell, 66: 65-75, 1991.
  • Ma, J. K.-C., Hiatt, A., Hein, M., Vine, N.D., Wang, F., Stabila, P., van Dolleweerd, C., Mostov, K., Lehner, T. Generation and assembly of secretory antibodies in plants. Science 268:716-719, 1995.
  • Luton, F., Vergés, M., Vaerman, J.-P., Sudol, M., and Mostov, K.E. The src family protein tyrosine kinase p62yes controls polymeric IgA transcytosis in vivo. Mol. Cell. 4:627-632, 1999.
  • Mostov, K.E., ter Beest, M., and Chapin, S.J. Catch the train to the basolateral surface. Cell. 99:121-122, 1999.
  • Zhang, J.-R., Mostov, K.E., Lamm, M.E., Nanno, M., Ohwaki, M., Shimada, S.-I., Ohwaki, M., and Tuomanen, E. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells, Cell:102:827-837, 2000.
  • O'Brien, L.E., Jou, T.-S., Pollack, A.L., Zhang, Q., Hansen, S.H., Yurchenco, P., and Mostov, K.E. Rac1 orients epithelial apical polarity through effects on basolateral laminin assembly. Nat. Cell Biol., 3:831-838, 2001.
  • von Zastrow, M. and Mostov, K. A new thread in an intricate web. Science. 294:1845-1847, 2001.
  • van IJzendoorn, S.C.D., Tuvim, M.J., Weimbs, T., Dickey, B.F., and Mostov, K.E. Direct interaction between Rab3b and the polymeric immunoglobulin receptor controls ligand-stimulated transcytosis in epithelial cells. Develop. Cell, 2:219-228, 2002.
  • O'Brien, L.E., Zegers, M.M.P., and Mostov, K.E. Opinion: Building epithelial architecture: insights from three-dimensional culture models. Nat. Rev. Mol. Cell Biol. 3:531-537, 2002.
  • Yu, W., O'Brien, L.E., Wang, F., Bourne, H., Mostov, K.E., and Zegers, M.M.P. HGF switches orientation of polarity and movement during morphogenesis of epithelial structures. Mol. Biol. Cell, 14:748-763, 2003.
  • Mostov, K.E. and Zegers, M.M.P. Just mix and patch. Nature, 422:267-268, 2003
  • Lipschutz,J.H., Lingappa,V.R. and Mostov, K.E. The exocyst affects protein synthesis by acting on the translocation machinery of the endoplasmic reticulum. J. Biol. Chem, 278:20954-20960, 2003.
  • Zegers, M.M.P., O'Brien, L.E., Yu, W., Datta, A., and Mostov, K.E. Epithelial polarity and tubulogenesis in vitro. Trends Cell Biol., 13:169-176, 2003
  • Mostov, K.E., Su, T., ter Beest, M. Polarized epithelial membrane traffic. Nat Cell Biol. 5:287-293, 2003.
  • Zegers, M.M.P, Forget, M.A., Chernoff, J., Mostov, K.E., ter Beest, M., Hansen, S.H. PAK1 and PIX regulate contact inhibition during epithelial wound healing. EMBO J., 22:4155-4165, 2003.
  • Kazmierczak, B. I., Mostov, K.E., and Engel, J. N. Epithelial cell polarity alters Rho-GTPase responses to Pseudomonas aeruginosa. Molecular Biology of the Cell, 15:411-419, 2004.
  • O'Brien, L.E., Tang., K., Kats E.S., Schutz-Geschwender, A., Lipschutz, J.A., Mostov, K.E., ERK and MMPs Sequentially regulate distinct stages of epithelial tubule development. Developmental Cell, 07:21-32, 2004.
  • Vergés, M., Luton, F., Gruber, C., L., Burlingame, A., Haft, C., Mostov K.E. The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor. Nature Cell Biology, 06:763-769, 2004.
  • Yu, W., Datta, A., Leroy, P., O'Brien, Mak, G., L.E., Jou, T.S., Matlin, K.S., Mostov, K.E., Zegers, M.M.P. 1-integrin orients epithelial polarity via Rac1 and laminin. Molecular Biology of the Cell. 16:433-445, 2004.
  • Tanimizu, N., Saito, H., Mostov, K., and Miyajima, A. Long-term culture of hepatic progenitors derived from mouse Dlk+ hepatoblasts. J. Cell Sci., 117:6425-6434, 2004.
  • Kierbel, A., Gassama-Diagne, A., Mostov, K, and Engel, J. N. The Phosphoinositol-3-kinase-Akt pathway is critical for Pseudomonas aeruginosa strain PAK internalization. Mol. Biol. Cell., 16:2577-2585, 2005.
  • ter Beest, M., Chapin, S. J., Avrahami, D., and Mostov, K. E. The role of syntaxins in the specificity of vesicle targeting in polarized epithelial cells. Mol Biol Cell, 16:5784-5792, 2005.
  • O'Brien, L.E., Yu, W., Tang, K., Jou, T.-S., Zegers, M.M.P., and Mostov, K.E. Morphological and biochemical analysis of Rac1 in three-dimensional epithelial cell cultures. Methods in Enzymology, 406:676-691, 2006.
  • Mostov, K. mTOR is out of control in polycystic kidney disease. PNAS, 103:5247-8, 2006
  • Fan, Q., Knight, Z. A., Goldenberg, D. D., Yu, W., Mostov, K., Stokoe, D., Shokat, K. M., Weiss, W. A. A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell, 9:341-349, 2006.
  • Gassama, A, Yu, W., Martin, F., Kierbel, A, , Engel, J., Mostov, K. . Phosphatidylinositol 3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cells. Nat. Cell Biol 8:963-970, 2006
  • Mostov, K. and Martin-Belmonte, F. The hole picture. Nature 442: 363-4, 2006.
  • Grant, M., Mostov, K., Tlsty, T., Hunt, C. A., Simulating Properties of In Vitro Epithelial Cell Morphogenesis. PLoS Computational Biology 2: e129, 1-17, 2006.
  • Reiter, J. and Mostov, K., Vesicle transport, cilium formation and membrane specialization: The origins of a sensory organelle. Proc. Natl. Acad. Sci. USA, 103:18383-4, 2006.