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Molecular Genetics

Purnima Dubey, PhD

 

Assistant Professor of Pathology

(Tumor Biology) and

Microbiology & Immunology


Email: pdubey@wfubmc.edu

 

Education:

Undergraduate:

University of Chicago, BA

 

Postgraduate:

University of Chicago, PhD, 1986

 

 

Research Interests:

Mechanisms of Anti-Tumor Immunity

 

Current Project(s):

Research in the laboratory focuses on two main areas: 1) the use of molecular imaging techniques to follow cellular anti-tumor immune responses in vivo, and 2) prostate cancer biology.

Recently developed molecular imaging techniques provide biologists with the ability to detect cellular and molecular interactions within the environment of the intact living subject. The use of radioisotoic and optical whole-body imaging modalities in combination can provide a sensitive readout of cell movement in real time. We have previously demonstrated in a mouse tumor model, that the localization of T cells to the site of the tumor can be detected using PET (positron emission tomography) imaging. Our goal is to follow lineage-specific and activation dependent anti-tumor T cell responses in vivo, using PET and bioluminescent optical imaging techniques. A murine bone marrow reconstitution model is under development to visualize the development of primary and secondary immune responses. We will utilize it to study the kinetics of T cell localization to experimental prostate cancers. We anticipate that this system can also be used for studies of autoimmunity as well as responses against viruses and other pathogens.

 

We are studying the role of Prostate Stem Cell Antigen (PSCA) in the development and progression of prostate cancer. PSCA is a GPI-anchored cell surface protein that is expressed in a restricted set of human and murine tissues, and is overexpressed in approximately 50% of human prostate cancers and bone metastases, and in a subset of bladder and pancreatic cancers. We and others have shown that murine PSCA is also overexpressed in experimental prostate cancers. Recent data from our lab suggests that the loss of PSCA expression leads to increased incidence of prostate cancer metastasis in a mouse model of prostate cancer. In order to determine the molecular basis for the putative growth control exerted by PSCA, we are currently examining the signaling pathways in which PSCA may be involved, as well as attempting to identify binding partners for PSCA.

 

 

 

Publications:

Akins E, Dubey P.  Non-invasive imaging of cell-mediated therapies for the treatment of cancer. J. Nucl. Med. 2007.  Submitted.

Moore ML, Teitell MA, Kim Y, Watabe T, Reiter RE, Witte ON, Dubey P. Deletion of PSCA increases metastasis of TRAMP-induced prostate tumors without altering primary tumor formation.  The Prostate  2007.  In Press.

Ali K, Dubey P, Roten S, Kute T. Effects of soy extracts on the growth of herceptin sensitive and resistant breast cancer cells in vitro and in vivo.  JNCAS 2006;122:19-28

Kim YJ, Dubey P, Ray P, Gambhir SS, Witte ON. Multimodality imaging of lymphocytic migration using lentiviral-based transduction of a tri-fusion reporter gene. Mol Imaging Biol. 2004 Sep-Oct;6(5):331-40.

Xin L, Ide H, Kim Y, Dubey P, Witte ON. In vivo regeneration of murine prostate from dissociated cell populations of postnatal epithelia and urogenital sinus mesenchyme. Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11896-903.

Dubey P, Su H, Adonai N, Du S, Rosato A, Braun J, Gambhir SS, Witte ON. Quantitative imaging of the T cell antitumor response by positron-emission tomography. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1232-7.

Ide H, Seligson DB, Memarzadeh S, Xin L, Horvath S, Dubey P, Flick MB, Kacinski BM, Palotie A, Witte ON. Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14404-9.

Dubey P, Wu H, Reiter RE, Witte ON. Alternative pathways to prostate carcinoma activate prostate stem cell antigen expression. Cancer Res. 2001 Apr 15;61(8):3256-61.

Wick M, Dubey P, Koeppen H, Siegel CT, Fields PE, Chen L, Bluestone JA, Schreiber H. Antigenic cancer cells grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy. J Exp Med. 1997 Jul 21;186(2):229-38.

Dubey P, Hendrickson RC, Meredith SC, Siegel CT, Shabanowitz J, Skipper JC, Engelhard VH, Hunt DF, Schreiber H. The immunodominant antigen of an ultraviolet-induced regressor tumor is generated by a somatic point mutation in the DEAD box helicase p68. J Exp Med. 1997 Feb 17;185(4):695-705.

Seung LP, Rowley DA, Dubey P, Schreiber H. Synergy between T-cell immunity and inhibition of paracrine stimulation causes tumor rejection. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6254-8.