Roselyn J. Eisenberg, Ph.D. Professor of Microbiology Primary Appointment with School of Veterinary Medicine Contact Information Robert Schattner Center University of Pennsylvania School of Dental Medicine Rm 216 Levy Building 240 South 40th Street Philadelphia, PA 19104-6030 Phone: 215-898-6552 Fax: 215-898-8385 Email: roselyn@biochem.dental.upenn.edu Web: University of Pennsylvania School of Medicine, Cell and Molecular Biology

Education/Professional Honors and Credentials

• Postdoctoral Fellow, Princeton University, Princeton, N.J.
  1966-1968
• Ph.D. in Microbiology, University of Pennsylvania, 1965
• A.B. in Biology, Bryn Mawr College, 1960
• Fellow, American Academy of Microbiologists
• Fellow, American Association for the Advancement of Science

Research Interests
Dr. Eisenberg's overall goal is to understand the mechanisms by which enveloped DNA viruses enter susceptible cells. Her research is a collaborative effort with long-term colleague, Dr. Gary H. Cohen, Professor and Chair of the Department of Microbiology at Penn Dental Medicine; while Dr. Eisenberg is a member of the School of Veterinary Medicine faculty with a secondary appointment at Penn Dental Medicine, her lab is at the Dental School with Dr. Cohen. Their research is primarily focused on the herpes simplex virus (HSV) and has more recently included work on poxvirus entry.

HSV entry requires the binding of glycoprotein D (gD) to either HVEM or nectin-1. This interaction triggers virus-cell fusion involving three other HSV glycoproteinsHVEM is a member of the TNF receptor superfamily. Nectin-1 is an adhesion molecule located at the gD adherens junctions of cells and is a member of the Ig superfamily. A major accomplishment was to solve the three-dimensional structure of gD bound to HVEM. The structure of this complex has enabled them to carry out structure-based mutagenesis of both proteins. Three additional gD structures have shown that the binding sites for both receptors are hidden in the native protein. Receptor binding necessitates a major conformational change in gD that is also required to properly trigger fusion. In collaboration with Drs. Katya Heldwein and Steve Harrison of Harvard Medical School, they solved the 3-dimensional structure of gB, a highly conserved protein that is a critical component of the fusion machinery. Studies to understand the structure and function of gH/gL, the other component of the fusion complex, is also an active area of the team's research.

Drs. Eisenberg and Cohen are exploring how the gD/receptor interaction triggers the next steps of virus entry and cell fusion. They are also using bimolecular complementation to follow protein-protein interactions that play important roles in the entry process and have found that gD triggers an interaction between gB and gH/gL simultaneously with the triggering of cell-cell fusion. Recent studies suggest that this interaction is a critical step, leading to fusion. In addition, one of the HSV receptors, HVEM, binds to a T-cell regulatory molecule called BTLA. This protein competes with HSV gD and the two researchers are investigating the significance of this competition for HSV pathogenesis.

Following the events of September 11, Drs. Eisenberg and Cohen began work on vaccinia virus (VACV) glycoproteins. A major goal of theirs is to develop a subunit vaccine against smallpox using proteins from VACV or from variola virus (smallpox) as a safer vaccine than the present one. Such a vaccine could be used for immunocompromised patients who cannot tolerate the current live virus vaccines and could also be used in a prime-boost strategy. A second goal is to understand the mechanism of VACV entry into cells, using techniques and approaches they have applied to studies of HSV entry. Importantly, they have shown that a combination of three envelope proteins of VACV protects mice against a lethal VV challenge. To understand the role of each of these proteins (and others) in poxvirus entry, the researchers are taking similar approaches to those used in their herpes virus work. VACV, like HSV, can use more than one pathway for entry and they also have evidence that at least one of the proteins being studied may be involved in receptor binding.

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