Robert Binder, Ph.D.
Campus: Biomedical Science Tower, 203 Lothrop Street
Pittsburgh PA 15261
- B.S. - University of Ghana
- Ph.D. - University of Connecticut
- Postdoc - University of Connecticut
- Professor, Department of Immunology
- Director, Program in Microbiology and Immunology
- Member, University of Pittsburgh Cancer Institute
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-receptor CD91 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 a 2M-substrate complexes and the potential of these immunogenic complexes to be used as therapeutic agents in cancer and infectious disease.
Sedlacek AL, Younker TP, Zhou YJ, Borghesi L, Shcheglova T, Mandoiu II, Binder RJ. (2019) CD91 on dendritic cells governs immunosurveillance of nascent, emerging tumors. JCI Insight. 4:7.
Binder RJ. (2019) Immunosurveillance of cancer and the heat shock protein-CD91 pathway. Cell Immunol. 2019 Sep;343:103814.
Kinner-Bibeau L.A., Sedlacek, A.L., Messmer, M.N., Watkins S.C., Binder, R.J. (2017). HSPs drive dichotomous T cell immune responses via DNA methylome remodelling in antigen presenting cells. Nat. Commun. 8, 15648 doi: 10.1038/ncomms15648.
Zhou YJ, Messmer MN, Binder RJ. (2014). Establishment of Tumor-Associated Immunity Requires Interaction of Heat Shock Proteins with CD91. Cancer Immunol Res. 2:217-228
Messmer MN, Pasmowitz J, Kropp LE, Watkins SC, Binder RJ. (2013). Identification of the Cellular Sentinels for Native Immunogenic Heat Shock Proteins In Vivo. J Immunol. 191:4456-4465.
Pawaria S, Kropp LE, Binder RJ. (2012). Immunotherapy of tumors with α2-macroglobulin-antigen complexes pre-formed in vivo. PLoS One. 7(11):e50365.
Pawaria S, Binder RJ. (2011). CD91-dependent programming of T helper cell responses following Heat Shock Protein immunization. Nat. Comm. 2011;2:521.
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, R.J. (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., 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.
Faculty of Biology “must read”. Commentary by Melief CJ., in the same issue.
Binder, R.J., and Srivastava, P.K. (2004). Essential role of CD91 in re-presentation of gp96-chaperoned peptides. Proc Natl Acad Sci U S A. 101, 6129-6133.
Faculty of Biology “must read”
Basu S, Binder RJ, Ramalingham T, Srivastava PK. (2001). CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70 and calreticulin. Immunity 14:303-313.
Binder RJ, Han D, Srivastava PK. (2000). CD91: a receptor for heat shock protein gp96. Nat Immunol 1: 151-155.
Commentary by Schild H, Rammensee HG., in same issue.