David S. Rubenstein, M.D., Ph.D., Associate Professor

Education/Degrees

  • Princeton University, Princeton, N.J. A.B. 1981-1985 Molecular Biology
  • Duke University, Durham, N.C. Ph.D. 1987-1992 Protein Chemistry
  • Duke University, Durham, N.C. M.D. 1985-1987, 1993 Medicine

Postgraduate Training and Professional Experience:

  • 1993-1994, University of Michigan Medical Center, Ann Arbor, MI, Dept. of Internal Medicine, Medical Internship
  • 1994-1997, University of North Carolina School of Medicine, Chapel Hill, NC, Department of Dermatology, Residency
  • 1996-1997, University of North Carolina School of Medicine, Chapel Hill, NC, Depts. of Dermatology and Biology, Post Doctoral Fellow
  • 1997-2003, University of North Carolina School of Medicine, Chapel Hill, NC, Dept. of Dermatology, Assistant Professor
  • 2003-present, University of North Carolina School of Medicine, Chapel Hill, NC, Dept. of Dermatology, Associate Professor
  • 1997-present, University of North Carolina Hospitals, Chapel Hill, NC, Dept. of Dermatology, Attending Physician

Research Interests

We are interested in understanding (i) how cells regulate their ability to adhere to one another, a process known as cell-cell adhesion and (ii) how cell-cell adhesion complexes might also function to transduce signals that “inform” the cell about the state of adhesion, a process known as signal transduction.

Current projects in the lab focus on the human proteins b-catenin and plakoglobin, which have dual roles in keratinocyte cell-cell adhesion and in mediating cellular signaling events.  b-catenin and plakoglobin are constituents of the adherens junction cell-cell adhesion complex.  Additionally, plakoglobin forms part of the desmosome cell-cell adhesion complex.  Desmogleins, constituents of the desmosome to which plakoglobin binds, are the target antigens for autoantibodies produced in the autoimmune blistering diseases pemphigus vulgaris and pemphigus foliaceus.

We are trying to understand the role these proteins play in cell-cell adhesion, cell-cell communication, and in autoimmune blistering diseases.  Through their participation in these studies, trainees will be exposed to a variety of cell biology and protein chemistry techniques including keratinocyte tissue culture, metabolic labeling, immunofluorescence microscopy, cell-fractionation, protein purification, SDS-PAGE, two-dimensional electrophoresis, immunoprecipitation, and western blotting.  Trainees initially participate in established ongoing projects in the lab, but are encouraged to develop independent areas of interest as their development progresses.  The lab environment has been developed to strongly encourage critical thinking.  Regularly scheduled lab meetings and as well as informal discussions provide opportunities for critical review of projects within our own lab as well as published literature relevant to our research interests.

Selected Publications

1.      Cavallo, R., Rubenstein, D., and Peifer, M. (1997) Armadillo and dTCF: A marriage made in the nucleus. Current Opinion in Genetics and Development7: 459-466.

2.      Hu, P., O’Keefe, E.J., and Rubenstein, D.S. (2001) Tyrosine phosphorylation of b-catenin and plakoglobin directly and reversibly regulates their binding to E-cadherin and a-catenin. J. Invest. Derm. 117: 1059-1067.

3.      Hu, P., Berkowitz, P., O'Keefe, E.J., and Rubenstein, D.S. (2003) Keratinocyte adherens junctions initiate nuclear signaling by translocation of plakoglobin from the membrane to the nucleus. J. Invest. Derm. 121: 242-251.

4.      Berkowitz, P., Hu, P., Kiu, Z., Enghild, J.J., Chua, M.P., and Rubenstein, D.S. (2005) Desmosome signaling: inhibition of p38MPAK prevents pemphigus vulgaris IgG induced cytoskeleton reorganization.  J. Biol. Chem., 280:23778-23784.

5.      Peiqi, H., Berkowitz, P., Madden, V., and Rubenstein, D. (2006) Stabilization of Plakoglobin and Enhanced Keratinocyte Cell-Cell Adhesion by Intracellular O-Glycosylation. J. Biol. Chem. 281:12786-12791.

6.      Berkowitz, P., Hu, P., Warren, S., Liu, Z., Diaz, L.A., Rubenstein, D.S. (2006)  p38MAPK inhibition prevents disease in pemphigus vulgaris mice.  Proc. Natl. Acad. Sci. USA. 103:12855-12860.