Robert Binder, PhD

  • Director, Graduate Program in Immunology & Microbiology
  • Associate Professor, Immunology

Education & Training

  • Graduate School – University of Connecticut – PhD - Immunology
  • Post-Doctoral School – University of Connecticut - Immunology

Research Grants

NIH Grants:  R21

Research Summary

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:

  1. HSPs chaperone peptides
  2. They bind to HSP-receptors (CD91) for endocytosis
  3. 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  2M-substrate complexes and the potential of these immunogenic complexes to be used as therapeutic agents in cancer and infectious disease.

Representative Publications

  1. Hatfield MJ, Binder RJ, Gannon R, Fratt EM, Bowling J, Potter PM. Potent, Irreversible Inhibition of Human Carboxylesterases by Tanshinone Anhydrides Isolated from Salvia miltiorrhiza ("Danshen"). J Nat Prod. 2018 Nov 26;81(11):2410-2418. doi: 10.1021/acs.jnatprod.8b00378. Epub 2018 Oct 23. PubMed PMID: 30351923; PubMed Central PMCID: PMC6263802.
  2. Wang Y, Sedlacek AL, Pawaria S, Xu H, Scott MJ, Binder RJ. Cutting Edge: The Heat Shock Protein gp96 Activates Inflammasome-Signaling Platforms in APCs. J Immunol. 2018 Oct 15;201(8):2209-2214. doi: 10.4049/jimmunol.1800505. Epub 2018 Sep 12. PubMed PMID: 30209191; PubMed Central PMCID: PMC6176107.
  3. Binder RJ. Immunosurveillance of cancer and the heat shock protein-CD91 pathway. Cell Immunol. 2018 May 16. pii: S0008-8749(18)30230-2. doi: 10.1016/j.cellimm.2018.05.007. [Epub ahead of print] PubMed PMID: 29784128; PubMed Central PMCID: PMC6239979.
  4. Binder RJ, Hatfield MJ, Chi L, Potter PM. Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors. Eur J Med Chem. 2018 Apr 10;149:79-89. doi: 10.1016/j.ejmech.2018.02.052. Epub 2018 Feb 19. PubMed PMID: 29499489; PubMed Central PMCID: PMC5863762.
  5. 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 (2017).
  6. Hatfield MJ, Chen J, Fratt EM, Chi L, Bollinger JC, Binder RJ, Bowling J, Hyatt JL, Scarborough J, Jeffries C, Potter PM. Selective Inhibitors of Human Liver Carboxylesterase Based on a β-Lapachone Scaffold: Novel Reagents for Reaction Profiling. J Med Chem. 2017 Feb 23;60(4):1568-1579. doi: 10.1021/acs.jmedchem.6b01849. Epub 2017 Feb 7. PubMed PMID: 28112927; PubMed Central PMCID: PMC5556379.
  7. Osei-Hwedieh DO, Kanias T, Croix CS, Jessup M, Xiong Z, Sinchar D, Franks J, Xu Q, M Novelli E, Sertorio JT, Potoka K, Binder RJ, Basu S, Belanger AM, Kim-Shapiro DB, Triulzi D, Lee JS, Gladwin MT. Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice. EBioMedicine. 2016 Sep;11:239-248. doi: 10.1016/j.ebiom.2016.08.006. Epub 2016 Aug 4. PubMed PMID: 27523807; PubMed Central PMCID: PMC5049931.
  8. Sedlacek AL, Kinner-Bibeau LB, Binder RJ. Phenotypically distinct helper NK cells are required for gp96-mediated anti-tumor immunity. Sci Rep. 2016 Jul 19;6:29889. doi: 10.1038/srep29889. PubMed PMID: 27431727; PubMed Central PMCID: PMC4949418.
  9. 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
  10. 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.