Reshef Lab

The Reshef lab combines efforts in both basic research and clinical investigation to advance the understanding of immune responses following hematopoietic cell transplantation and other forms of cell therapy.

The lab is focused on two primary areas:

1. Identifying novel targets in graft-versus-host disease and development of therapeutic interventions:
   1. T-cell migration - the lab pioneered the use of chemokine receptor blockade after allogeneic hematopoietic cell transplantation to reduce graft-versus-host disease.
   2. The enteroendocrine system – we study the role of glucagon-like peptides in the mucosal immune system and their potential therapeutic use in graft-versus-host disease.
2. Single-cell methodologies for the study of human samples – we aim to unravel novel mechanisms that would lead to new therapeutic approaches in immune-mediated diseases. We use a diverse toolset that includes genomic and immunophenotypic methods to identify new targets that improve transplant and cell therapy outcomes.

Publications

1. Bansal R, Park H, Taborda CC, Gordillo C, Mapara MY, Assal A, Uhlemann AC, Reshef R. “Antibiotic exposure, not alloreactivity, is the major driver of microbiome changes in hematopoietic cell transplantation.” Transplant Cell Therapy 2021.
2. Reshef R, Saber W, Bolaños-Meade J, Chen G, Chen YB, Ho VT, Ponce DM, Nakamura R, Martens MJ, Hansen JA, Levine JE. “Acute GVHD Diagnosis and Adjudication in a Multicenter Trial; a Report from the BMT CTN 1202 Biorepository Study.” J Clin Oncol 2021.
3. Macedo R, Pasin C, Ganetsky A, Harle D, Wang XK, Belay K, Richman LP, Huffman AP, Vonderheide RH, Yates AJ, Porter DL, Wang Y, Zhang Y, Reshef R. “Vitamin D deficiency after allogeneic hematopoietic cell transplantation promotes T-cell activation and is inversely associated with an EZH2-ID3 signature.” Transplant Cell Therapy 2021.
4. Zewde MG, Morales G, Gandhi I, Özbek U, Aguayo-Hiraldo P, Ayuk F, Baez J, Chanswangphuwana C, Choe H , DeFilipp Z, Etra A, Grupp S, Hexner EO, Hogan W, Javorniczky NR, Kasikis S, Kitko CL, Kowalyk S, Meedt E, Merli P, Nakamura R, Qayed M, Reshef R, Rösler W, Schechter T, Weber D, Wölfl M, Yanik G, Young R, Levine JE, Ferrara JLM, Chen YB. “Evaluation of elafin as a prognostic biomarker in acute graft-versus-host disease.” Transplant Cell Therapy 2021.
5. Lopez-Bujanda ZA, Obradovic A, Nirschl TR, Crowley L, Macedo R, Papachristodoulou A, O’Donnell T, Laserson U, Zarif JC, Reshef R, Yuan T, Soni MK, Antonarakis ES, Haffner MC, Larman HB, Shen MM, Muranski P, Drake CG. “TGM4: An Immunogenic Prostate-Restricted Antigen” J Immunother Cancer 2021.
6. Mayor NP, Wang T, Lee SJ, Kuxhausen M, Vierra-Green C, Barker DJ, Auletta J, Bhatt VR, Gadalla SM, Gragert L, Inamoto Y, Morris G, Paczesny S, Reshef R, Ringdén O, Shaw BE, Shaw P, Spellman SR, Marsh SGE. “Impact of previously unrecognized HLA mismatches using ultra-high resolution typing in unrelated donor hematopoietic cell transplantation” J Clin Oncol 2021.
7. Gordillo CA, Parmar S, Blanco M, Delille EM, Assal A, Mapara MY, Reshef R. “Gastrointestinal Toxicity of High-Dose Melphalan in Autologous Hematopoietic Stem Cell Transplantation: Identification of Risk Factors and a Benchmark for Experimental Therapies” Ann Hematol 2021.
8. Pasin C, Moy RH, Reshef R, Yates AJ. “Variable selection methods for predicting clinical outcomes following allogeneic hematopoietic cell transplantation” Sci Rep 2021.
9. Bolaños-Meade J*, Reshef R*, Fraser R, Fei M, Abhyankar S, Al-Kadhimi Z, Alousi AM, Antin JH, Arai S, Bickett K, Chen YB, Damon LE, Efebera YA, Geller N, Giralt SA, Hari P, Holtan SG, Horowitz MM, Jacobsohn DA, Jones RJ, Liesveld JL, Logan BR, MacMillan ML, Mielcarek M, Noel P, Pidala J, Porter DL, Pusic I, Sobercks R, Solomon S, Weisdorf DJ, Wu J, Pasquini MC*, Koreth J*. “Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomized phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203).” Lancet Haematology 2019. *Equal contribution
10. Reshef R, Ganetsky A, Acosta E, Blauser R, Crisalli L, McGraw J, Frey N, Hexner E, Hoxie J, Loren A, Luger S, Mangan J, Stadtmauer E, Mick R, Vonderheide R, Porter D. “Extended CCR5 Blockade for Graft-Versus-Host Disease Prophylaxis Improves Outcomes of Reduced Intensity Unrelated Donor Hematopoietic Cell Transplantation: A Phase II Clinical Trial” Biol Blood Marrow Transplant 2019.
11. Hartwell MJ, Ozbek U, Holler E, Renteria AS, Major-Monfried H, Reddy PR, Aziz M, Hogan WJ, Ayuk FA, Efebera YA, Hexner EO, Bunworasate U, Qayed M, Ordemann R, Woelfl M, Mielke S, Pawarode A, Chen YB, Devine SM, Harris AC, Jagasia MH, Kitko CL, Litzow MR, Kroger N, Locatelli F, Morales G, Nakamura R, Reshef R, Rosler W, Weber D, Wudhikarn K, Yanik GA, Levine JE, Ferrara JLM. “An Early Biomarker Algorithm Predicts Lethal Graft-versus-Host Disease and Survival” J Clin Invest Insight 2018.
12. Huffman AP, Richman LP, Crisalli L, Ganetsky A, Porter DL, Vonderheide RH, Reshef R. “Pharmacodynamic Monitoring Predicts Outcomes of CCR5 Blockade as GVHD Prophylaxis” Biol Blood Marrow Transplant 2018.
13. Moy RH, Huffman AP, Richman LP, Crisalli L, Wang XK, Hoxie JA, Mick R, Emerson SE, Vonderheide RH, Porter DL, Reshef R. “Clinical and Immunologic Impact of CCR5 Blockade in Graft-Versus-Host Disease Prophylaxis” Blood 2017.
14. Huang Q, He S, Tian Y, Gu Y, Chen P, Li C, Huang J, Liu Y, Jin M, Hu S, Tong Q, Ma A, Jin J, Hexner E, Fung H, Reshef R, Zhang Y, Zhang Y. “Hsp90 inhibition destabilizes Ezh2 protein in alloreactive T cells and reduces graft-versus-host disease in mice” Blood 2017.
15. He S, Liu Y, Meng L, Sun H, Wang Y, Ji Y, Purushe J, Chen P, Li C, Madzo J, Issa JP, Soboloff J, Reshef R, Moore BB, Gattinoni L, Zhang Y. “Ezh2 Phosphorylation State Determines its Capacity to Maintain CD8+ T Memory Precursors for Antitumor Immunity” Nat Commun 2017.
16. Meng L, Bai Z, He S, Mochizuki K, Liu Y, Purushe J, Sun H, Wang J, Yagita H, Mineishi S, Fung H, Yanik GA, Carrichio R, Fan X, Crisalli LM, Hexner EO, Reshef R, Zhang Y, Zhang Y. “The Notch ligand DLL4 defines a unique capability of human dendritic cells in regulating Th1 and Th17 differentiation” J Immunol 2016.
17. Hexner EO, Luger SM, Reshef R, Jeschke GR, Mangan JK, Frey NV, Frank DM, Richman LP, Vonderheide RH, Aqui NA, Rosenbach M, Zhang Y, Chew A, Loren AW, Stadtmauer EA, Levine BL, June CH, Emerson SG, Porter DL. “Infusion of CD3/CD28 co-stimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment” Am J Hematol 2016.
18. Mochizuki K, Meng L, Mochizuki I, Tong Q, He S, Liu Y, Purushe J, Fung H, Zaidi RM, Zhang Y, Reshef R, Blazar BR, Yagita H, Mineishi S, Zhang Y. “Programming of Donor T Cells Using Allogeneic Delta-like ligand 4-positive Dendritic Cells to Reduce GVHD in Mice” Blood 2016.
19. Lefebvre E, Moyle G, Reshef R, Richman LP, Thompson M, Hong F, Chou HI, Hashiguchi T, Plato C, Poulin D, Richards T, Yoneyama H, Jenkins H, Wolfgang G, Friedman SL. “Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis” PLOS One 2016.
20. Karimi M, Bryson JL, Richman LP, Fesnak AD, Leichner TM, Satake A, Vonderheide RH, Raulet DH, Reshef R, Kambayashi T. “NKG2D expression by CD8+ T-cells contributes to GVHD and GVT effects in a murine model of allogeneic HSCT” Blood 2015.
21. Reshef R, Huffman AP, Gao A, Luskin MR, Hexner EO, Loren AW, Frey NV, Stadtmauer EA, Luger SM, Mangan JK, Nasta SD, Gill SI, Sell M, Kambayashi T, Richman LP, Vonderheide RH, Mick R, Porter DL. “High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection In Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning” J Clin Oncol 2015.
22. Kumar AJ, Hexner EO, Frey NV, Luger SM, Loren AW, Reshef R, Boyer J, Smith J, Stadtmauer EA, Levine BL, June CH, Porter DL, Goldstein SC. “Pilot Study of Prophylactic Ex Vivo Co-Stimulated Donor Leukocyte Infusion After Reduced Intensity Conditioned Allogeneic Stem Cell Transplantation.” Biol Blood Marrow Transplant 2013.
23. Hardy NM, Fellowes V, Rose JJ, Hakim FT, Odom J, Pittaluga S, Steinberg SM, Blacklock-Schuver B, Avila DN, Memon S, Kurlander RJ, Khuu HM, Stetler-Stevenson M, Mena Gonzalez E, Dwyer AJ, Levine BL, June CH, Reshef R, Vonderheide RH, Gress RE, Fowler DH, Hakim FT, Bishop MR. “Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation.” Blood 2012.
24. Reshef R, Luger SM, Hexner EO, Loren AW, Frey NV, Nasta, SD, Goldstein SC, Stadtmauer EA, Smith J, Bailey S, Mick R, Heitjan DF, Emerson SG, Hoxie J, Vonderheide RH, Porter DL. “Effect of Blocking Lymphocyte Chemotaxis on Visceral Graft-vs-Host Disease.” N Engl J Med 2012.
25. Beatty GL, Smith JS, Reshef R, Patel KP, Colligon TA, Vance BA, Frey NV, Johnson FB, Porter DL, Vonderheide RH (2009). “Functional unresponsiveness and replicative senescence of myeloid leukemia antigen- specific CD8+ T cells after allogeneic stem cell transplantation.” Clin Cancer Res 2009.