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E1040
Thomas E. Starzl Biomedical Science Tower
Phone: 412-383-9737
Fax: 412-383-8098
Faculty
 
binder.jpg Robert J. Binder , Ph.D.
Associate Professor
E1051 BSTWR
200 Lothrop St.
Pittsburgh, PA 15261
Phone: 412.383.7722
Email: rjb42@pitt.edu
Fax: 412.383.8096
Faculty Research Interests
 
Research Interests
Our research interests are focused on the mechanisms of cross-priming of antigens during immune responses to cancer, viruses and autoimmunity. The pursuit of this area stems from the observations that in a good number of situations Heat Shock Proteins (HSPs) are both necessary and sufficient for cross-presentation. HSPs are adept at this because of several unique properties:

(i) HSPs chaperone peptides

(ii) They bind to HSP-receptors (CD91) for endocytosis

(iii)They can stimulate immune cells to up-regulate costimulation

HSPs thus elicit remarkable immune responses specific for the peptides they chaperone. The laboratory is using these observations to examine new facets of antigen presentation and also to develop novel ways of immunotherapy of cancer, infectious disease and autoimmune disorders. A related area of research examines how other ligands for the HSP-receptorCD91 interact with the immune system. In the past few years we have shown that a2-macroglobulin, a CD91 ligand, though not a bonafide HSP, shares the immunogenic properties of HSPs and can elicit immune responses specific to (peptide) substrates that it chaperones. We are currently exploring the identification of naturally formed a2M-substrate complexes and the potential of these immunogenic complexes to be used as therapeutic agents in cancer and infectious disease.
 
Education
B.S. - University of Ghana

Ph.D. - University of Connecticut

Postdoc - University of Connecticut
 
Academic Affiliation
Associate Professor, Department of Immunology, University of Pittsburgh School of Medicine

Director, Tumor Immunology, UPCI summer academy
 
Selected Publications
Messmer, M.N., Pasmowitz, J, Kropp, L.E., Watkins, S.C., and Binder, R.J. (2013) Identification of the cellular sentinels for native immunogenic Heat Shock Proteins in vivo. J. Immunol. (in press)

Pawaria, S., Kropp, L.E., and Binder, R.J. (2012). Immunotherapy of tumors with 2-macroglobulin-antigen complexes pre-formed in vivo. PLoS One. 2012;7(11):e50365.

Pawaria, S., and Binder, R.J. (2011). CD91-dependent programming of T helper cell responses following Heat Shock Protein immunization. Nat Commun. 2:521. doi: 10.1038/ncomms1524

Pawaria, S., Messmer, M.N., Zhou, Y.J., and Binder, R.J. (2011). A role for the heat shock protein-CD91 axis in the initiation of immune responses to tumors. Immunol Res. 50, 255-260

Kropp, L.E., Garg, M. and Binder, RJ. (2010). Ovalbumin-derived precursor peptides are transferred sequentially from gp96 and calreticulin to MHC I in the endoplasmic reticulum. J Immunol. 184, 5619-5627.

Binder, R.J. (2009). CD40-independent engagement of mammalian hsp70 by antigen presenting cells. J. Immunol. 182, 6844-6850.

De Filippo, A., Binder, R.J., Camisaschi, C., Beretta, V., Arienti, F., Villa, A., Mina, P.D., Parmiani, G., Rivoltini, L., and Castelli, C. (2008). Human plasmacytoid dendritic cells interact with gp96 via CD91 and regulate the onset of inflammatory responses. J. Immunol. 181, 6525-6535.

Binder, R.J., Vatner, R.E., Kelly, J.B., and Srivastava, P.K. (2007). Immunogenicity of purified heat shock protein gp96 derives from endogenously bound antigenic peptides and not from contaminating proteins. J. Immunol. 179, 7254-7261.

Binder, R.J., and Srivastava, P.K. (2005). Peptides chaperoned by heat-shock proteins are a necessary and sufficient source of antigen in the cross-priming of CD8+ T cells. Nat Immunol. 6, 593-599.

SenGupta, D., Norris, P.J., Suscovich, T.J., Hassan-Zahraee, M., Moffett, H.F., Trocha, A., Draenert, R., Goulder, P.J., Binder, R.J., Levey, D.L., Walker, B.D., Srivastava, P.K., Brander, C. (2004) Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II. J. Immunol. 173, 1987-1993.
 
Grants
Title: Role of CD91 and its ligands in immune response
Agency: NIH
Role: P.I.
Funding Period: 2009-2014

Title: Role for alpha2-macroglobulin in Immune responses and cancer immunotherapy
Agency: NIH
Role: P.I.
Funding Period: 2008-2012
 
Lab Personnel
Douglas Feck- Research assistant

Abigail Sedlacek, PhD- Post doctoral fellow
Yu Mizote, PhD- Post doctoral Fellow

Lauren Kinner- graduate student
Michelle Messmer- graduate student
Yu Jerry Zhou- graduate student
 
 


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