Biological and Biomedical Science
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Daniel A. Goodenough

Department of Cell Biology
Harvard Medical School
220 Longwood Avenue
Boston, MA 02115
Tel: (617) 432-1652
Fax: (617) 432-2955
Email: daniel_goodenough@hms.harvard.edu
Web Page: The Goodenough Lab Page
2 postdoctoral fellows

Cells in tissues and organs are almost universally joined to each other by gap junctions: clusters of low-resistance channels that allow intercellular diffusion of ions and small metabolites.  The intercellular channels are composed of connexins, a family of proteins with broad cell and tissue distributions.  Targeted connexin gene knockouts in mice and phenotypes in human mutants reveal essential functions for gap junctional intercellular communication in cataract, demyelinating diseases, deafness and cardiovascular function.  The molecular bases for these phenotypic changes are under investigation.

Our laboratory is also studying the zonula occludens, or tight junction, which regulates passage of ions and solutes between cells of an epithelial sheet (the paracellular pathway).  Tight junction-specific proteins, such as occludin and the claudins, are being expressed in cultures of epithelial cells, which are then studied using physiological methods.  In addition, mice carrying transgenes expressing shRNA are being developed to knock down claudin expression in the kidney, in order to study the contributions of the paracellular pathway to ion homeostasis. 

 

References:

  • Calera, M., H.L. Topley, Y. Liao, B.R. Duling, D.L. Paul and D.A. Goodenough 2006 Connexin43 is required for production of the aqueous humor in the murine eye. J. Cell Sci. 119:4510-4519.

  • Hou, J. A.S. Gomes, D.L. Paul and D.A. Goodenough 2006 Study of claudin function by RNA interference J. Biol. Chem. 281:36117-36123.

  • Hou, J., Q. Shan, T. Wang, A.S. Gomes, Q. Yan, D.L. Paul, M. Bleich, and D.A. Goodenough 2007 Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. J. Biol. Chem. 282:17114-17122.

  • Hou, J., A. Renigunta, M. Konrad, A.S. Gomes, E.E. Schneeberger, D.L. Paul, S. Waldegger and D.A. Goodenough 2008 Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. J. Clin. Invest. 188:619-628.