Deborah H. Spector

Virology and Vaccine Development

Deborah H. Spector, Ph.D.

Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences
Department of Cellular and Molecular Medicine
Telephone: (858) 822-4003
Email: dspector@ucsd.edu

Research Summary: Herpesviruses – Cell Biology and Vaccine Development

Dr. Spector's lab has spent the past 31 years studying human cytomegalovirus (HCMV), which is the major viral cause of birth defects, a serious problem in immunocompromised individuals, and a risk factor in atherosclerosis. Her research centers on viral pathogenesis and the molecular mechanisms used by HCMV to control its gene expression and subvert the cell's signaling and regulatory pathways. A key discovery was that HCMV modulates the ubiquitin-proteasome pathway by inactivating the anaphase promoting complex, the major E3 ubiquitin ligase in cell cycle regulation.
Dr. Spector's group has also developed a novel strategy for vaccines against viruses that persist and establish latency, and has shown their protective efficacy in animal models of cytomegalovirus infection and genital HSV-2 infection. The underlying principle is that herpesviruses persist because natural immunity cannot eliminate the infected cells, and thus vaccination must be more effective in establishing protection than natural infection. The vaccine includes 1) DNA plasmids expressing specific viral gene products that elicit a protective immune response following immunization but not natural infection and 2) viral particles in adjuvant.

Academic Achievements

Education: B.A. in Biology (1971) Smith College; Ph.D. in Cell and Molecular Biology (1975) MIT; Postdoctoral Research (1975-78) UCSF.
Awards and Honors: Phi Beta Kappa; Sigma Xi; NSF Grad Fellowship (1971-74); Helen Hay Whitney Foundation Postdoc. Fellowship (1975-78); Kaiser Permanente Teaching Award (1983, 1985); Visiting Professor, Hubei Medical College, Wuhan, China (10/86); Tribute to Women In Industry Award (1995).
Leadership Experience: Founding Chair, Molecular Biology Section in Division of Biological Sciences 2000-03; Chair, American Society for Microbiology, DNA Viruses Section, 2004-05; UCSD Clinical and Translational Res. Institute. – Director Translational Res. Alliance Program 2008 - Present.

Teaching

* Cellular and Molecular Basis of Disease (SOM 204).
* From the Molecule to the Organism (BIOM 200).
* Advanced Animal Virology (BGGN 226).
* Microbiology and Infectious Diseases Therapeutics (SPPS 246B).
* Medical Microbiology (SOM 208).

Key Contributions to Pharmaceutical Sciences

* Original discovery that the retroviral oncogene src is conserved in vertebrate genomes-(research with Dr. J. Michael Bishop and Dr. Harold Varmus).
* Developed nucleic acid probes and techniques for screening and diagnosing human cytomegalovirus infections - US Patent 4762780.
* Developed vaccine strategy for viruses that cause persistent and latent infections.
* Solved problem of constructing translationally-inducible complementing primary cell lines for viruses with mutations in essential toxic genes.

Selected Recent Publications

(PubMed List)
Morello et al. (2005). Systemic prime-boost immunization with a trivalent plasmid DNA and inactivated murine cytomegalovirus (MCMV) vaccine provides long-term protection against viral replication following systemic or mucosal MCMV challenge. J. Virol. 79:159-175.
Morello et al. (2007). DNA immunization using the highly conserved murine cytomegalovirus genes encoding the homologs of human cytomegalovirus UL54 (DNA polymerase) and UL105 (helicase) elicits strong CD8 T responses and is protective against systemic challenge. J. Virol. 81:7766-7775.
Tran et al. (2008). Accumulation of substrates of the anaphase-promoting complex (APC) during human cytomegalovirus infection is associated with the phosphorylation of cdh1 and the dissociation and relocalization of the APC subunits. J. Virol. 82:529-537.
Sanders et al. (2008). Development of cell lines that provide tightly controlled temporal translation of the human cytomegalovirus IE2 proteins for complementation and functional analyses of growth-impaired and non-viable IE2 mutant viruses. J Virol. 82:7059-7077.

Potential Collaborative Programs with the Pharmaceutical Industry

* 31 years of expertise in herpes virus research and vaccine development Broad array of laboratory techniques in virology, immunology, molecular and cell biology, and in vivo viral pathogenesis.