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Guido
Silvestri
Associate
Professor, Pathology, Microbiology and Immunology
Gene
Therapy and Vaccines Program
Microbiology, Virology and Parasitology Program
Address
Office
Suite 705 Stellar-Chance Laboratories
422 Curie Boulevard
Philadelphia, PA 19104
215-573-5363
Lab
703 Stellar-Chance Laboratories
422 Curie Boulevard
Philadelphia, PA 19104
215-573-5368
Fax: 215-573-5369
E-mail: gsilvest@mail.med.upenn.edu
Link(s)
Dr.
Silvestri's Micro Dept Page
Education
University of Ancona: MD, 1987.
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Research
Interests
- Pathogenesis of HIV infection. Development of AIDS vaccines.
Key words: HIV, AIDS, SIV, T-cells, apoptosis,
cell cycle.
Description
of Research
Our laboratory is interested in understanding
the pathogenesis of the AIDS-associated depletion of CD4+
T lymphocytes. In particular, we are interested in the mechanisms
by which SIV infection of natural hosts, such as the sooty
mangabeys (an African monkey species) is not followed by CD4+
T cell depletion and AIDS despite chronic high levels of viral
replication. This circumstance is strikingly different from
the HIV infection of humans, or the SIV infection of non-natural
hosts, i.e. rhesus macaques. Our studies focus on the host
determinants that determine the rate of T cell depletion and
progression to AIDS, and on the role that the host cellular
immune responses play in suppressing virus replication, or
alternatively, in inducing pathogenic consequences. We plan
to apply these concepts to (i) the development of new, immune-based
therapies for HIV infection (i.e., IL-2, IL-7) to be used
in addition to standard antiretroviral therapy, and (ii) the
design of T-cell- based AIDS vaccines that will generate memory
T cell responses against HIV/SIV that may confer significant
protection while not inducing any relevant immunopathology.
Selected
Publications
Gordon SN, Engram J, Milush JM, Dunham R, Klatt N, Strobert EA, Apetrei C, Pandrea I, Staprans SI, Sodora DL, Silvestri G. Severe depletion of mucosal CD4+
T-cells in AIDS-free SIV-infected sooty mangabeys. J Immunol, 2007; 179-3026-
3034.
Gordon SN, Dunham RM, Engram JC, Estes J, Wang Z, Klatt NR, Pandrea IV,
Apetrei C, Sodora DL, Lee HY, Haase AT, Miller MD, Kaur A, Staprans SI, Perelson
AS, Feinberg MB, Silvestri G. Short-lived infected cells support virus
replication in naturally SIV-infected sooty mangabeys: implications for AIDS
pathogenesis. J Virol, 2008, 82:3713-3724.
Dunham R, Cervasi B, Brenchley J, Albrecht H, Weintrob A, Sumpter B, Engram
J, Gordon S, Klatt N, Piedimonte G, Sodora D, Douek D, Paiardini M, Silvestri G.
Expression of the IL-2 and IL-7 receptor on CD4+ T cells defines cell subsets
that are differentially depleted during HIV-infection. J Immunol, 2008;
180:5582-92.
Klatt NR, Villinger F, Bostik P, Gordon SN, Pereira L, Engram JC, Mayne A,
Dunham R, Lawson B, Sodora DL, Else J, Reimann K, Staprans SI, Estes JD,
Silvestri G, Ansari AA. Availability of activated CD4+ T-cells is a major
determinant of set-point viremia during natural SIV Infection of sooty mangabeys
J Clin Invest, 2008, 118:2039-49.
Paiardini M, Cervasi B, Engram JC, Gordon S, Klatt N, Muthukumar A, Else J,
Staprans SI, Sodora DL, Silvestri G. Bone marrow-based homeostatic proliferation
of mature T-cells in non-human primates: implications for AIDS pathogenesis.
Blood, in press
Search PubMed for more articles
Lab
Rotation
Projects
- Pathogenesis of SIV infection in natural
hosts
- Mechanisms of apoptosis in HIV infection
- Il-7R signaling and AIDS pathogenesis
- Bone marrow dysfunction in HIV/SIV infection
- Lab
personnel
Jessica Engram, lab manager
Mirko Paiardini, PhD, research associate
Barbara Cervasi, PhD, post-doctoral fellow
Thomas Vanderford, Ph.D, post-doctoral fellow
Steven Bosinger, Ph.D, post-doctoral fellow
Katrina Nolan, Ph.D, post-doctoral fellow
Jill Adamski, M.D., Ph.D, post-doctoral fellow
Beth Cramer, graduate student
Nikki Klatt, graduate student
Alex Ortiz, graduate student
Jessica Taaffe, graduate student
last updated 7/2008
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