- Postdoc - University of Connecticut
- Ph.D. - University of Connecticut
- B.S. - University of Ghana
Education & Training
Harkness T, Nayak DA, Sedlacek A, Cattley R, Hawse WF, Watkins SC, Binder RJ. CD91-mediated reprogramming of DCs by immunogenic heat shock proteins requires the kinases AXL and Fgr. Cell Commun Signal (2024).
Devanshi A. Nayak, Abigail L. Sedlacek, PhD, Anthony Cillo, PhD, Simon Watkins, PhD, Robert J Binder, PhD. CD91 and its ligand gp96 confer cross-priming capabilities to APCs during immune responses against nascent, emerging tumors. Cancer Immunol Res (2024).
Osei-Hwedieh DO, Sedlacek AL, Hernandez LM, Yamoah AA, Iyer SG, Weiss KR, Binder RJ.. Immunosurveillance shapes the emergence of sarcomas with distinct neoepitope landscapes revealing specific tumor-type antigenic differences. JCI Insight. 2023 Jul 10;8(13):e170324. PMID: 37427594
Jacqueline C, Dracz M, Xue J, Binder RJ, Minden J, Finn O. LCVM infection generates tumor antigen-specific immunity and inhibits growth of nonviral tumors. Oncoimmunology. 2022 Jan 21;11(1):2029083. PMID: 35083098
Sedlacek AL, Kinner-Bibeau LB, Wang Y, Mizes AP, Binder RJ. Tunable heat shock protein-mediated NK cell responses are orchestrated by STAT1 in Antigen Presenting Cells. Sci Rep. 2021 Aug 9;11(1):16106. PMID: 34373574
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.
Our research interests are focused on the mechanisms of cancer and viral immunosurveillance. The pursuit of this area of immunology stems from the observations that (i) Heat Shock Protein (HSP) binding to their cognate receptor CD91 on antigen presenting cells (APC) elicits potent cross-priming of T cell responses and activation of NK cells, and (ii) CD91 is indispensable for immunosurveillance. HSPs are adept at this because they chaperone antigenic peptides from the cells of origin and allow for efficient CD91-dependent cross-presentation of antigens by the APC. Engagement of CD91 by HSPs also allows the APC to provide co-stimulation and cytokines for T cell priming.
The laboratory has a mechanistic emphasis and is using these observations to examine new facets of antigen presentation, cell signaling, and tumor immunosurveillance in animal models and in humans. The laboratory uses a combination of cellular immunology, systems immunology, and biochemical approaches to probe these scientific avenues.
The disease emphasis of the laboratory is to develop new ways of immunotherapy of cancer and infectious disease with a focus on HSPs and other CD91 ligands as therapeutic modalities and vaccines. This is explored both in animal models and in humans. Other APC receptors are being examined in this area. In collaboration with clinicians at the UPMC Hillman Cancer Center and elsewhere, we are also examining cancer patient samples for markers of immune reactivity to understand why some individuals fail immunosurveillance and possible remedies.