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Faculty Pramod K. Srivastava
Professor of Medicine
srivastava@nso2.uchc.edu
- Physician Health Services Chair in Cancer Immunology
- Ph.D., Center for Cellular and Molecular Biology, Hyderabad, India
- Immunology Graduate
Program
- Accepting students for Lab Rotations: Summer '08, Fall '08,
Spring '09
Areas of Interest:
Our laboratory’s research interests lie in four areas: antigen
presentation by MHC I and MHC II molecules, immune response to cancer,
viral immunity, and autoimmunity. Our pursuit of these areas is linked
to a key set of observations made by our laboratory over the past 20
years. These observations are: (1) Heat shock proteins (HSP) isolated
from cells are always associated with a broad array of peptides. These
peptides are derived from the proteins present in the cell and together,
the HSP-associated peptide profile represents the total protein/peptide
repertoire of a cell including the antigenic repertoire. (2) The HSP-peptide
complexes, whether isolated from cells, or reconstituted in vitro,
are potent immunogens against the peptides and cells presenting those
peptides. The immune response elicited by such complexes is heavily
skewed towards a cellular T cell response. (3) HSPs have remarkable
immunomodulatory properties which derive from their interaction with
macrophage and dendritic cells through a receptor, identified by us as
CD91. Our laboratory has used these observations to explore new key
aspects of antigen presentation and to develop innovative approaches for
therapy of cancer, infections and autoimmune disorders. It is our view
that the HSP-peptide interaction is an evolutionary precursor to the MHC-peptide
interaction and lies at the center of a wide array of immunological
phenomena.
Lab Rotation Projects:
The following constitutes most of what we do. Students are encouraged to
create rotation projects out of any of these areas.
(1) We study antigen presentation and cross-priming. We have
uncovered a key role of heat shock proteins, the most highly conserved
and abundant proteins in living systems, in both of these phenomena,
which are central to immunology.
(2) Our studies with heat shock proteins have lead to novel
approaches to immunotherapy of cancers and infectious diseases, which
are in Phase 3 clinical trials in over 200 hospitals worldwide.
(3) We have also shown heat shock proteins to elicit regulatory
CD4+ T cells; the mechanism of this phenomenon as well as its
application to therapy of autoimmune diseases are of continuing interest
to us.
(4) This laboratory has a new-found interest in neuro-immunology.
We do not have much of a track record in this area, as we just published
our first paper in it. Our interest is driven by the many observations
that demonstrate a clear link between the nervous and the immune
systems. We aim to explore those links through new phenomena and their
mechanisms at the molecular, cellular and organismal levels.
Publications
Selected Publications:
Binder RJ, Srivastava P. Peptides chaperoned by heat-shock proteins
are necessary and sufficient for priming CD8+ T cells. Nature Immunol.,
2005, May 1, in press.
Basu S, Srivastava P. Immunological role of neuronal receptor
vanilloid receptor 1 expressed on dendritic cells. Proc Natl Acad Sci U
S A. 2005 Apr 5;102(14):5120-5.
Binder RJ, Srivastava PK. Essential role of CD91 in re-presentation
of gp96-chaperoned peptides. Proc. Natl. Acad. Sci: USA,
101(16):6128-6133, 2004.
Chandawarkar RY, Wagh MS, Kovalchin JT, Srivastava PK. Immune
modulation with high dose of heat shock protein gp96: Therapy of murine
autoimmune diabetes and encephalomyelitis. Intl Immunology, 16
(4):615-624, 2004.
Basu S, Srivastava PK. Fever-like temperature induces maturation of
dendritic cells through induction of hsp90. Intl Immunology,
15(9):1053-61, 2003.
Srivastava PK. Hypothesis : Controlled necrosis as a tool for
immunotherapy of human cancer. Cancer Immunity, Vol. 3, pg 4, 2003.
Rivoltini L, Castelli C, Carrabba M, Mazzaferro V, Pilla L, Huber V,
Coppa J, Gallino G, Scheibenbogen C, Squarcina P, Cova A, Camerini R,
Lewis JJ, Srivastava PK, Parmiani G. Human Tumor-Derived Heat Shock
Protein 96 Mediates In Vitro Activation and In Vivo Expansion of
Melanoma and Colon Carcinoma-Specific T Cells. J. Immunology,
171(7):3467-3474, 2003.
Srivastava P. Interaction of heat shock proteins with peptides and
antigen presenting cells: chaperoning of the innate and adaptive immune
responses. Annu Rev Immunol. 2002;20:395-425.
Binder RJ, Kumar A, Srivastava PK. Naturally formed or artificially
reconstituted non-covalent 2-macroglobulin-peptide complexes elicit
CD91-dependent cellular immunity. Cancer Immunity, 2 :16, 2002.
Panjwani NN, Popova L, Srivastava PK. Heat shock proteins gp96 and
hsp70 activate release of Nitric Oxide by antigen presenting cells. J.
of Immunology, 168 (6), 2997-3003, 2002.
Makki A, Weidt G, Blachere N, LeFrancois L, and Srivastava PK.
Abrogation of tumore protection by immunization against a dominant tumor
antigen. Cancer Immunity, Vol. 2, pg. 4, 2002.
Ménoret A, Li Z, Niswonger ML, Altmeyer A, Srivastava PK. An
endoplasmic reticulum protein implicated in chaperoning peptides to
major histocompatibility of class I is an aminopeptidase. Journal of
Biological Chemistry, 276: 33313-33318, 2001.
Somersan S, Larsson M, Fonteneau JF, Basu S, Srivastava PK, and
Bhardwaj N. Primary tumor tissue lysates are enriched in heat shock
proteins and induce the maturation of human dendritic cells. J. of
Immunology, 167: 4844-4852, 2001.
Binder RJ, Blachere NE, Srivastava PK. Heat shock protein-chaperoned
peptides but not free peptides introduced into the cytosol are presented
efficiently by major histocompatibility complex I molecules. J Biol
Chem. 2001 May 18;276(20):17163-71.
Srivastava PK. Immunotherapy of human cancer: lessons from mice.
Nature Immunol. 2000 Nov;1(5):363-6.
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