William R Green, PhD
Professor of Micro Immunology
The Elmer R. Pfefferkorn Professor of Microbiology and Immunology
Case Western Reserve University, Ph.D. 1977
University of Michigan, BS 1972
Molecular and Cellular Biology Graduate Programs
Norris Cotton Cancer Center
Program in Experimental and Molecular Medicine
Geisel School of Medicine at Dartmouth
Borwell Research Bldg., HB 7556
1 Medical Center Drive
Lebanon NH 03756
T Cell Immune Responses to Retroviral Diseases
The primary interests of the lab focus on cell-mediated immunity to mouse retroviruses that cause either leukemia or immunodeficiency. We have been studying resistance to endogenous AKR/Gross virus-induced leukemia mediated by cytotoxic T lymphocyte (CTL) responses. By use of "low leukemia" mouse strains, CTL that readily lyse AKR/Gross retrovirus-induced tumors have been generated. The CTL recognize "type-specific" viral determinants with the major immunodominant viral peptide located in the transmembrane anchor protein encoded by the envelope gene. Other mouse strains of higher leukemia incidence are unable to generate such CTL responses. The mechanism of unresponsiveness include both MHC-dependent mechanisms and apoptosis of effector CTL following interaction with FasL-expressing virus infected cells.
Another area of emphasis is the study of both immunity to the mouse acquired immunodeficiency syndrome (MAIDS) retroviral isolate and the mechanism of retroviral pathogenesis. In this model of HIV induced AIDS, we have raised unique protective CTL to the causative virus. Interestingly, the immunodominant determinant recognized by the CTL is encoded by a previously unrecognized alternative viral translational reading frame. Moreover, this alternative reading frame is extended, and mutagenesis experiments have shown that it exists because its protein product is necessary for viral pathogenesis. . We are also interested in the retroviral induction of myeloid-derived suppressor cells (MDSC) in this system: especially their unique inhibition of B-cell immune responsiveness (as well as of T-cell responses), and the first report in any system of involvement of the new checkpoint regulator VISTA in MDSC suppression of B-cell activity.
Rotations and Thesis Projects:
1. Reciprocal modulation of CD4T reg cells and MDSCs
2. Involvement of VISTA in MDSC inhibition of B-cell responses
3. MDSC suppressive effector mechanisms in addition to iNOS/NO
P20RR16437/P30GM103415 (Phase III) Green, W.R. (PI) 09/01/2001-06/30/2016
$1,215,000/yr. total costs
Center of Biomedical Research Excellence in Molecular, Cellular, and Translational Immunology
The goals of this COBRE application are to increase the numbers of investigators in New Hampshire who are competitive in securing NIH extramural funding and to establish a Molecular, Cellular, and Translational Immunological Research Center of Biomedical Research Excellence (COBRE). Role: PI
1UL1TR001086-01 (Green, Alan I.) 09/26/2013 – 4/30/2018
1KL2TR001088-01 IAC chairman, other
NIH/NCATS $4,000,000/yr. total institutional interface
Dartmouth SYNERGY: The Dartmouth Clinical and Translational Science Institute
The overarching goal of this project is to create an integrated home for clinical and translational science at Dartmouth and accelerate the translation of scientific knowledge into practice and improved population health.
BIOL 42 Biology of the Immune Response -- Course Co-Director
After graduation from Case Western Reserve, Dr. Green first continued his efforts with an NIH supported fellowship and then working as a research associate in Immunology first at the Johns Hopkins University School of Medicine and then at the Fred Hutchinson Cancer Research Center (FHCRC) and the University of Washington (UW) in Seattle becoming an Assistant Member/Professor at FHCRC and the UW in 1980. Dr. Green joined the faculty of the Department of Microbiology at Dartmouth Medical School in 1983. From 1992-2002 Dr. Green served as Director of the Immunology Program, including the Immunology and Cancer Immunotherapy Program of the Norris Cotton Cancer Center, before becoming Chair of the Microbiology and Immunology (M/I) Department in July, 2002; and leading as PI the NIH-NIGMS funded Center of Biomedical Research Excellence (COBRE) in Molecular, Cellular, and Translational Immunological Research, now in its fourteenth year of funding. From January, 2008 through September 2010, he served one term as Dean of Dartmouth Medical School before returning to chairmanship of the M/I Department, and Director of the Dartmouth Community Medical School.
Approximately equal number of Ph.D. graduate students and post-doctoral fellows trained over 25+ years.
Long term PI of an NIH/NIAID Institutional (T32) Training Grant funding graduate students and postdoctoral fellows in immunology.
PI of the Immunology COBRE Award from the NIH for 14 years and ongoing – including junior faculty development.
Rastad JL, Green WR. LP-BM5 Retrovirus-Expanded Monocytic Myeloid-Derived Suppressor Cells Alter B Cell Phenotype and Function. Immunohorizons. 2018 Mar 30;2(3):87-106. (view details on MedLine)
O'Connor MA, Rastad JL, Green WR. The Role of Myeloid-Derived Suppressor Cells in Viral Infection. Viral Immunol. 2017 Mar;30(2):82-97. (view details on MedLine)
Rastad JL, Green WR. Myeloid-derived suppressor cells in murine AIDS inhibit B-cell responses in part via soluble mediators including reactive oxygen and nitrogen species, and TGF-β. Virology. 2016 Dec;499:9-22 (view details on MedLine)
O'Connor MA, Vella JL, Green WR. Reciprocal relationship of T regulatory cells and monocytic myeloid-derived suppressor cells in LP-BM5 murine retrovirus-induced immunodeficiency. J Gen Virol. 2016 Feb;97(2):509-22. (view details on MedLine)
O'Connor MA, Fu WW, Green KA, Green WR. Subpopulations of M-MDSCs from mice infected by an immunodeficiency-causing retrovirus and their differential suppression of T- vs B-cell responses. Virology. 2015 Nov;485:263-73 (view details on MedLine)
Green KA, Wang L, Noelle RJ, Green WR. Selective Involvement of the Checkpoint Regulator VISTA in Suppression of B-Cell, but Not T-Cell, Responsiveness by Monocytic Myeloid-Derived Suppressor Cells from Mice Infected with an Immunodeficiency-Causing Retrovirus. J Virol. 2015 Sep;89(18):9693-8. (view details on MedLine)
Lizotte PH, Baird JR, Stevens CA, Lauer P, Green WR, Brockstedt DG, Fiering SN. Attenuated Listeria monocytogenes reprograms M2-polarized tumor-associated macrophages in ovarian cancer leading to iNOS-mediated tumor cell lysis. Oncoimmunology. 2014 May 23;3:e28926 (view details on MedLine)
O'Connor MA, Green WR. Use of IRF-3 and/or IRF-7 knockout mice to study viral pathogenesis: lessons from a murine retrovirus-induced AIDS model. J Virol. 2014 Feb;88(4):2349-53. (view details on MedLine)
Green KA, Cook WJ, Green WR Myeloid-derived suppressor cells in murine retrovirus-induced AIDS inhibit T- and B-cell responses in vitro that are used to define the immunodeficiency. J Virol 2013 Feb; 87:2058-71 (view details on MedLine)
O'Connor MA, Green WR. The role of indoleamine 2,3-dioxygenase in LP-BPM5 murine retroviral disease progression. Virol J. 2013 May 17;10:154. (view details on MedLine)