Brian <span>C.</span> Betts
Researcher

Brian C. Betts

Overview

To understand how human T-cell signal transduction mediates GVHD, and to apply such knowledge toward novel GVHD prevention trials.

Discipline

    • Blood and Marrow Transplant and Cellular Immunotherapy
    • Immunology
    • Immunology

Education & Training

    • Eastern Virginia Medical School, MD
    • University of Minnesota, Resident - Internal Medicine
    • University of Minnesota, Chief Resident - Internal Medicine
    • Memorial Sloan Kettering Cancer Center, Fellow - Hematology/Oncology
Research

Brian C. Betts, MD, is an assistant professor in the Department of Blood and Marrow Transplantation at Moffitt Cancer Center.  He received his Doctorate of Medicine at Eastern Virginia Medical School in 2004.  He completed his internal medicine residency at the University of Minnesota in 2007, and served as chief resident from 2007-2008.  He went on to complete his subspecialty training in hematology and medical oncology at Memorial Sloan Kettering Cancer Center in 2011, where he served as chief fellow from 2009-2010. Dr. Betts is a member of Alpha Omega Alpha and an Amy Strelzer Mansevit Research Program Scholar.  Dr. Betts studies how human T-cell signal transduction may be controlled to prevent harmful graft-versus-host disease (GVHD) and preserve beneficial graft-versus-leukemia (GVL) after allogeneic hematopoietic cell transplantation.  As a fellow in Dr. James Young’s lab at Memorial Sloan Kettering, he demonstrated that JAK2 is a relevant target to control alloreactivity and maintain regulatory T-cells (Treg).  More recently under the mentorship of Dr. Claudio Anasetti, Dr. Betts collaborated with Moffitt colleague, Dr. Joseph Pidala, to provide evidence that STAT3 activity is significantly elevated in circulating CD4+ T-cells before acute GVHD onset. Additionally, he has shown that targeting STAT3 polarizes the differentiation of potent, stable, inducible human Tregs.  Overall, he is interested in bringing such concepts to novel clinical investigations with the goal to reduce GVHD and spare GVL independent of broad immune suppression.

Publications

  • Betts BC, Pidala J, Kim J, Mishra A, Nishihori T, Perez L, Ochoa-Bayona JL, Khimani F, Walton K, Bookout R, Nieder M, Khaira DK, Davila M, Alsina M, Field T, Ayala E, Locke FL, Riches M, Kharfan-Dabaja M, Fernandez H, Anasetti C. IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation. Haematologica. 2017 May;102(5):948-957. Pubmedid: 28104702. Pmcid: PMC5477614.
  • Betts BC, Veerapathran A, Pidala J, Yang H, Horna P, Walton K, Cubitt CL, Gunawan S, Lawrence HR, Lawrence NJ, Sebti SM, Anasetti C. Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining Treg and antitumor CTL function. Sci Transl Med. 2017 Jan;9(372). Pubmedid: 28077684.
  • Curran SA, Shyer JA, St Angelo ET, Talbot LR, Sharma S, Chung DJ, Heller G, Hsu KC, Betts BC, Young JW. Human Dendritic Cells Mitigate NK-Cell Dysfunction Mediated by Nonselective JAK1/2 Blockade. Cancer Immunol Res. 2017 Jan;5(1):52-60. Pubmedid: 27923824. Pmcid: PMC5335862.
  • Tees MT, Betts B, Hillgruber R, Ayala E, Field T, Kharfan-Dabaja MA, Locke F, Mishra A, Nishihori T, Ochoa-Bayona JL, Perez L, Pidala J, Anasetti C, Fernandez H, Riches ML. New sources for argument: do HLA-C and HLA disparity in adult double umbilical cord blood transplants predict outcomes?. Bone Marrow Transplant. 2016 Sep;51(9):1256-1258. Pubmedid: 27088383.
  • Heinrichs J, Bastian D, Veerapathran A, Anasetti C, Betts B, Yu XZ. Regulatory T-Cell Therapy for Graft-versus-host Disease. J Immunol Res Ther. 2016 Oct;1(1):1-14. Pubmedid: 27722210. Pmcid: PMC5049884.
  • Heinrichs J, Li J, Nguyen H, Wu Y, Bastian D, Daethanasanmak A, Sofi MH, Schutt S, Liu C, Jin J, Betts B, Anasetti C, Yu XZ. CD8(+) Tregs promote GVHD prevention and overcome the impaired GVL effect mediated by CD4(+) Tregs in mice. Oncoimmunology. 2016 Jun;5(6):e1146842. Pubmedid: 27471614. Pmcid: PMC4938369.
  • Nelson R, Shapiro JF, Perkins JB, Kim J, Nishihori T, Pidala J, Ayala E, Locke FL, Field T, Mishra A, Riches M, Betts B, Perez L, Yue B, Ochoa-Bayona JL, Alsina M, Fernandez H, Anasetti C, Kharfan-Dabaja MA. Sirolimus, tacrolimus and antithymocyte globulin as GVHD prophylaxis in HLA-mismatched unrelated donor hematopoietic cell transplantation: a single institution experience. Bone Marrow Transplant. 2015 Nov;50(11):1487-1489. Pubmedid: 26301969. Pmcid: PMC4863975.
  • Pidala J, Bloom GC, Eschrich S, Sarwal M, Enkemann S, Betts BC, Beato F, Yoder S, Anasetti C. Tolerance associated gene expression following allogeneic hematopoietic cell transplantation. PLoS One. 2015 Mar;10(3):e0117001. Pubmedid: 25774806. Pmcid: PMC4361657.
  • Pidala J, Kim J, Betts BC, Alsina M, Ayala E, Fernandez HF, Field T, Kharfan-Dabaja MA, Locke FL, Mishra A, Nishihori T, Ochoa-Bayona L, Perez L, Riches M, Anasetti C. Ofatumumab in combination with glucocorticoids for primary therapy of chronic graft-versus-host disease: phase I trial results. Biol Blood Marrow Tr. 2015 Jun;21(6):1074-1082. Pubmedid: 25805300.
  • Pidala J, Kim J, Alsina M, Ayala E, Betts BC, Fernandez HF, Field T, Jim H, Kharfan-Dabaja MA, Locke FL, Mishra A, Nishihori T, Ochoa-Bayona L, Perez L, Riches M, Anasetti C. Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease. Haematologica. 2015 Jul;100(7):970-977. Pubmedid: 25840599. Pmcid: PMC4486232.
  • Betts B, Anasetti C, Pidala J. Biomarkers for GVHD prognosis. Lancet Haematol. 2015 Jan;2(1):e4-e5. Pubmedid: 26687427.
  • Betts BC, Sagatys EM, Veerapathran A, Lloyd MC, Beato F, Lawrence HR, Yue B, Kim J, Sebti SM, Anasetti C, Pidala J. CD4+ T cell STAT3 phosphorylation precedes acute GVHD, and subsequent Th17 tissue invasion correlates with GVHD severity and therapeutic response. J Leukoc Biol. 2015 Apr;97(4):807-819. Pubmedid: 25663681. Pmcid: PMC4370048.
  • Kunter G, Perkins JB, Pidala J, Nishihori T, Kharfan-Dabaja MA, Field T, Fernandez H, Perez L, Locke F, Ayala E, Tomblyn M, Ochoa-Bayona JL, Betts B, Nieder M, Anasetti C. Pharmacokinetically-targeted BU and fludarabine as conditioning before allogeneic hematopoietic cell transplantation for adults with ALL in first remission. Bone Marrow Transplant. 2014 Jan;49(1):11-16. Pubmedid: 23995098.
  • Betts BC, Veerapathran A, Pidala J, Yu XZ, Anasetti C. STAT5 polarization promotes iTregs and suppresses human T-cell alloresponses while preserving CTL capacity. J Leukoc Biol. 2014 Feb;95(2):205-213. Pubmedid: 24068731. Pmcid: PMC3896660.
  • Veerapathran A, Pidala J, Beato F, Betts B, Kim J, Turner JG, Hellerstein MK, Yu XZ, Janssen W, Anasetti C. Human regulatory T cells against minor histocompatibility antigens: ex vivo expansion for prevention of graft-versus-host disease. Blood. 2013 Sep;122(13):2251-2261. Pubmedid: 23908471. Pmcid: PMC3785121.
  • Pidala J, Kim J, Schell M, Lee SJ, Hillgruber R, Nye V, Ayala E, Alsina M, Betts B, Bookout R, Fernandez HF, Field T, Locke FL, Nishihori T, Ochoa JL, Perez L, Perkins J, Shapiro J, Tate C, Tomblyn M, Anasetti C. Race/ethnicity affects the probability of finding an HLA-A, -B, -C and -DRB1 allele-matched unrelated donor and likelihood of subsequent transplant utilization. Bone Marrow Transplant. 2013 Mar;48(3):346-350. Pubmedid: 22863723. Pmcid: PMC4500122.
  • Romano E, Cotari JW, Barreira da Silva R, Betts BC, Chung DJ, Avogadri F, Fink MJ, St Angelo ET, Mehrara B, Heller G, Münz C, Altan-Bonnet G, Young JW. Human Langerhans cells use an IL-15R-α/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1. Blood. 2012 May;119(22):5182-5190. Pubmedid: 22510877. Pmcid: PMC3369609.
  • Pidala J, Kim J, Jim H, Kharfan-Dabaja MA, Nishihori T, Fernandez HF, Tomblyn M, Perez L, Perkins J, Xu M, Janssen WE, Veerapathran A, Betts BC, Locke FL, Ayala E, Field T, Ochoa L, Alsina M, Anasetti C. A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation. Haematologica. 2012 Dec;97(12):1882-1889. Pubmedid: 22689677. Pmcid: PMC3590095.
  • Betts BC, Young JA, Ustun C, Cao Q, Weisdorf DJ. Human herpesvirus 6 infection after hematopoietic cell transplantation: is routine surveillance necessary?. Biol Blood Marrow Tr. 2011 Oct;17(10):1562-1568. Pubmedid: 21549850. Pmcid: PMC3285510.
  • Pidala J, Kim J, Anasetti C, Nishihori T, Betts B, Field T, Perkins J. The global severity of chronic graft-versus-host disease, determined by National Institutes of Health consensus criteria, is associated with overall survival and non-relapse mortality. Haematologica. 2011 Nov;96(11):1678-1684. Pubmedid: 21791465. Pmcid: PMC3208686.
  • Betts BC, Abdel-Wahab O, Curran SA, St Angelo ET, Koppikar P, Heller G, Levine RL, Young JW. Janus kinase-2 inhibition induces durable tolerance to alloantigen by human dendritic cell-stimulated T cells yet preserves immunity to recall antigen. Blood. 2011 Nov;118(19):5330-5339. Pubmedid: 21917753. Pmcid: PMC3217413.
  • Betts BC, St Angelo ET, Kennedy M, Young JW. Anti-IL6-receptor-alpha (tocilizumab) does not inhibit human monocyte-derived dendritic cell maturation or alloreactive T-cell responses. Blood. 2011 Nov;118(19):5340-5343. Pubmedid: 21940820. Pmcid: PMC3217414.
  • Betts BC, Young JW. Tregs served sunny-side up. Blood. 2010 Dec;116(23):4736-4737. Pubmedid: 21127180.