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Vicente Planelles, Ph.D.
Associate Professor
Vicente Planelles, Ph.D
About Vicente Planelles, Ph.D.
HIV-1 encodes four accessory proteins, Vif, Vpr, Vpu and Nef. These are small proteins with multiple functions, and regulate various aspects of the virus-host cell relationship. My laboratory has primarily focused on Vpr. Vpr induces cell cycle arrest in the G2 phase. The immediate consequence of this activity of Vpr is that infected cells do not enter mitosis and, therefore, do not divide. A later consequence of the cell cycle disturbance is that the infected cell commits to apoptosis or programmed cell death. We hypothesize that this chain of events explains, at least in part, the severe depletion in CD4-positive lymphocytes observed during the acquired immunodeficiency syndrome.
A major research objective of my laboratory is to understand, at a molecular level, the succession of signaling events that ultimately lead to the induction of apoptosis. We have found that Vpr interferes with the normal DNA replication of dividing cells. This interference, in turn activates a cellular system that monitors the integrity of DNA as well as the processivity of DNA replication. This system is known as the ATR serine-threonine kinase.
Through activation of the ATR kinase, Vpr accomplishes the activation of two different, but interdependent signaling cascades, leading to cell cycle disruption and apoptosis.
Selected Publications
- Roshal M, Zhu Y, Kim B, Nghiem P, Planelles V: Activation of ATR-Mediated DNA Damage Response by the HIV-1 Viral Protein R. J Biol Chem 278:25879-86, 2003.
- DeHart JL, Andersen JL, Zimmerman ES, Ardon O, An D, Blackett J, Planelles V: ATR is dispensable for retroviral integration. J Virol 79:1389-96, 2005.
- Zimmerman ES, Sherman MP, Blackett JL, Neidleman JA, Kreis C, Mundt P, Williams SA, Warmerdam M, Kahn J, Hecht FM, Grant RM, de Noronha CM, Weyrich AS, Greene WC, Planelles V: HIV-1 Vpr induces DNA replication stress in vitro and in vivo. J Virol 80:10407-10418, 2006.
- Andersen JL, DeHart JL, Zimmerman ES, Ardon A, Kim B, Jacquot G, Benichou S and Planelles V: HIV-1 Vpr-induced apoptosis is cell-cycle dependent and requires Bax but not ANT. PLOS pathogens 2:e127, 2006.
- DeHart JL, Zimmerman ES, Ardon O, Monteiro-Filho CMR, Argañaraz ER, Planelles V: HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system. Manuscript submitted
- All Publications: Click Here
Honors and Awards
- 1998 Searle-Donald F. Richardson Prize Paper at the ACOG District II Junior Fellows Annual Meeting in New York City.
- 1999 Annual Clinical Meeting of ACOG in Philadelphia, to Dr. E. Toy for presentation “Human Immunodeficiency Virus Type 1 Viral Protein R Induces Cell-Cycle Arrest in Cervical Cancer Cells” Toy E, Rodríguez-Rodríguez L and Planelles V.
- 1995 Amgen, Inc. Postdoctoral Fellowship.
- 1991-1994 National Institute of Health (NIH) Training Fellowship.
- 1987-1991 Graduate Research Assistantship, University of California, Davis, CA.
- 1985 F.O.C.U.S. Award for Achievement in Academic Research, Seville, Spain.
Professional Education
- Baccalaureate Degree 1984 B.S. (Biological Sciences) Universidad Complutense, Madrid, Spain
- Masters Degree 1985 M.S. (Plant Physiology) Universidad Complutense, Madrid, Spain
- Advanced Degree 1991 Ph.D. (Immunology and Virology) University of California, Davis, CA