Geoffrey Hill, M.D.

RESEARCH

The Hill laboratory focuses on transplant immunology and continues to span basic discovery research and translational clinical practice, utilizing cutting-edge immunological techniques including advanced cell and whole organism imaging, flow cytometry, proteomics and RNASeq. The studies have focused on addressing the major limitations of bone marrow transplantation, namely graft-versus-host disease (GVHD), opportunistic infection, relapse and graft rejection. Studies in the GVHD setting have focused on understanding the mechanisms of alloantigen presentation, T cell differentiation (both effector and regulatory) and cytokine biology where we have led the field with a number of pivotal late phase translational clinical studies underway. My work in opportunistic infections has focused on CMV and understanding the immunological requirements for virus control. We have developed the first models of CMV reactivation after allogeneic BMT that allow preclinical testing of immunomodulation strategies to improve pathogen-specific immunity. Studies in GVHD biology have allowed us to interrogate strategies to enhance leukemia-specific immunity and focus on modulating pathways of cytokine signaling and antigen presentation. Finally, we are in the late stages of small-molecule development to inhibit perforin in order to eliminate graft rejection.

PUBLICATIONS

1. Hill GR, Crawford JM, Cooke KR, et al. Total body irradiation and acute graft-versus-host disease. The role of gastrointestinal damage and inflammatory cytokines. Blood 1997; 90:3204-3213. PMID: 9376604
2. Kennedy GA, Varelias A, Vuckovic S, et al (Hill Snr author). Addition of interleukin-6 inhibition with tocilizumab to standard graft-versus-host disease prophylaxis after allogeneic stem-cell transplantation: a phase 1/2 trial. Lancet Oncol. 2014;15(13):1451-1459. PMID: 25456364
3. Koyama M, Kuns RD, Olver SD, et al (Hill Snr author). Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease. Nat Med. 2012;18(1):135-142. PMID: 22127134
4. Koyama M, Cheong M, Markey KA, et al. (Hill Snr author). Donor colonic CD103+ dendritic cells determine the severity of acute graft-versus-host disease. J Exp Med. 2015, 212(8):1303-21. PMID: 26169940. PMCID: PMC4516799.
5. Koyama M, Mukhopadhyay P, Schuster I, et al. (Hill Snr author). MHC class II antigen presentation by the intestinal epithelium initiates graft-versus-host disease and is influenced by the microbiota. Immunity 2019; Sep 16. pii: S1074-7613(19)30362-0. doi: 10.1016/j.immuni.2019.08.011. PMID: 31542340
6. Zhang P, Lee JS, Gartlan KH, et al (Hill Snr author). Eomesodermin promotes the development of type 1 regulatory T cells. Science Immunol. 2017; 2(10). eaah7152. PMID: 28738016. PMCID:PMC5714294.
7. Varelias A*, Bunting MD*, Ormerod KL, et al (Hill Snr author). Recipient Mucosal-Associated Invariant T Cells control GVHD within the colon. J Clin Invest. 2018, 128:1919-1936. PMID: 29629900. PMCID: PMC5919881.
8. Minnie SA, Kuns RD, Gartlan KH, et al (Hill Snr author). Myeloma-escape after stem cell transplantation is a consequence of T cell exhaustion and is reversed by TIGIT inhibition.  Blood 2018; 132:1675-1688.
9. Vuckovic S, Minnie S, Smith D, et al (Hill Snr author). Bone marrow transplantation generates T cell-dependent myeloma control in mice. J Clin Invest. 2019; 129(1):106-121.
10. Martins JP, Andoniou CE, Fleming P, Kuns RD, Daly S, Schuster IS, Varelias A, Tey SK, Degli-Esposti MA* and Hill GR*. Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation. Science. 2019. 363(6424):288-293. co-senior author. PMID: 30655443.

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