Adam J. Adler, PhDProfessor of ImmunologyVice Chair, Graduate Programs Committee
|
Degree | Institution | Major |
---|---|---|
BSc | McGill University | Physiology |
MA | Columbia University | Molecular Biology and Biochemistry |
MPhil | Columbia University | Molecular Biology and Biochemistry |
PhD | Columbia University | Molecular Biology and Biochemistry |
Post-Graduate Training
Training | Institution | Specialty |
---|---|---|
Postdoctoral | Johns Hopkins School of Medicine, Department of Oncology | Postdoctoral Fellow in the Laboratory of Dr. Drew Pardoll |
Awards
Name of Award/Honor | Awarding Organization |
---|---|
Oncology Fellows Day Award | Johns Hopkins School of Medicine |
Postdoctoral Fellowship | American Cancer Society |
American Foundation for Urologic Disease Scholar | Urology Care Foundation |
Summer Student Fellowship | Medical Research Council of Canada |
Name & Description | Category | Role | Type | Scope | Start Year | End Year |
---|---|---|---|---|---|---|
NIH ZRG1 F09-A (08) L Fellowship: Oncological Sciences | Other | Member | External | National | 2012 | 2012 |
Search Committee for the Flow Cytometry Core Facility Director | Advisory Committee | Member | UConn Health | University | 2011 | 2011 |
Education Council | Education Committee | Member | UConn Health | University | 2011 | 2013 |
Search Committee for the MD/PhD Program Director | Advisory Committee | Member | UConn Health | University | 2011 | 2011 |
Faculty Search Committee for Connecticut Children’s Medical Center | Advisory Committee | Member | UConn Health | University | 2011 | 2011 |
NIH ZRG IMM-C 02 M and IMM-N (03) M | Other | Member | External | National | 2011 | 2011 |
PhD admissions committee | Advisory Committee | Member | UConn Health | University | 2011 | 2011 |
Grant Writing Workshop organized by the Office of Research and Sponsored Programs | Workshop/Conference | Participant | UConn Health | University | 2011 | |
Search Committee for the Department of Immunology Chair | Advisory Committee | Member | UConn Health | University | 2010 | 2011 |
Search Committee for the Associate Dean of the Graduate School | Advisory Committee | Member | UConn Health | University | 2010 | 2010 |
Immunology Graduate Program | Advisory Committee | Director | UConn Health | University | 2010 | 2013 |
PO1 “Autoimmunity” (ZAI1-PTM-1-M3) | Other | Member | External | National | 2010 | 2010 |
PO1 “Regulatory T cells in Autoimmune and Inflammatory Diseases” (ZAI1-SV-I-M1) | Other | Member | External | National | 2010 | 2010 |
“Director's Opportunity 5 Themes Immunology” (ZRG1 IMM-E (55) R), NIH | Other | Member | External | National | 2010 | 2010 |
Immunology Panel for Prostate Cancer Research Program (PCRP), CDMRP | Advisory Committee | Ad Hoc Member | External | National | 2010 | 2010 |
Site Visit Review Team of NCI Cancer and Inflammation Program, NIH | Advisory Committee | Member | External | National | 2010 | 2010 |
Flow Cytometry Core Facility Advisory Committee | Advisory Committee | Member | UConn Health | University | 2009 | |
Viral Vector Core Facility Advisory Committee | Advisory Committee | Member | UConn Health | University | 2007 | 2010 |
Immunology Graduate Program | Advisory Committee | Director | UConn Health | University | 2007 | 2010 |
Graduate Program Committee | Advisory Committee | Member | UConn Health | University | 2007 | 2013 |
Prostate Cancer Research Program Study Section, Department of Defense | Study Section | Ad Hoc Member | External | National | 2007 | 2008 |
Italian Association for Cancer Research | Advisory Committee | Preferred Grant Reviewer | External | International | 2007 | |
ZRG1 TTT-G “Immunology of Tolerance” Study Section, NIH | Study Section | Ad Hoc Member | External | National | 2006 | 2006 |
Special Emphasis Panel PO1 “T Cell Tolerance” (ZAI1-PA-I-M3), NIH | Study Section | Chair | External | National | 2006 | 2006 |
Transplantation, Tolerance, and Tumor Immunology (TTT) Study Section, NIH | Study Section | Member | External | National | 2006 | 2010 |
The Journal of Immunology | Editorial Board | Associate Editor | External | National | 2006 | 2010 |
Health Center Research Advisory Committee | Advisory Committee | Member | UConn Health | University | 2005 | |
Transplantation, Tolerance and Tumor Immunology (TTT) Study Section, NIH | Study Section | Ad Hoc Member | External | National | 2005 | 2005 |
PhD admissions committee | Advisory Committee | Member | UConn Health | University | 2005 | 2006 |
Current Immunology Reviews | Editorial Board | Member | External | National | 2004 | |
Cancer Research UK | Study Section | Ad Hoc Grant Reviewer | External | International | 2003 | 2003 |
Special Emphasis Allergy and Immunology Study Section, NIH | Study Section | Ad Hoc Grant Reviewer | External | National | 2003 | 2003 |
Experimental Immunology Study Section, NIH | Study Section | Ad Hoc Grant Reviewer | External | National | 2003 | 2004 |
Department of Veterans Affairs’ Medical Research Service | Study Section | Ad Hoc Grant Reviewer | External | National | 2001 | 2002 |
Cancer Immunity | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
Cancer Research | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
Cell Stress & Chaperones | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
Current Immunology Reviews | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
Cytokine | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
European Journal of Immunology | Editorial Board | Ad Hoc Journal Reviewer | External | International | ||
Immunology | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
Immunology Letters | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
International Immunology | Editorial Board | Ad Hoc Journal Reviewer | External | International | ||
Journal of Leukocyte Biology | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
Medicinal Research Reviews | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
PLoS ONE | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
The Journal of Experimental Medicine | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
The Journal of Immunology | Editorial Board | Ad Hoc Journal Reviewer | External | National | ||
Health Center Research Advisory Committee (HCRAC) | Advisory Committee | member, and member of emergency grant subcommittee | UConn Health | University | ||
Research Council | Advisory Committee | member | UConn Health | University | ||
Institutional Animal Care and Use Committee (IACUC) | Research Committee | member | UConn Health | University | ||
Graduate Program Committee (GPC) | Education Committee | member | UConn Health | University | ||
Flow Cytometry Core Advisory Committee | Advisory Committee | member | UConn Health | University | ||
Biomedical Sciences Curriculum Committee | Education Committee | member | UConn Health | University |
Research InterestsT lymphocytes have the potential to eliminate tumors. Although tumor vaccines have been able to activate tumor-specific T cells and achieve modest clinical efficacy in treating human cancer patients, they are generally not curative because tumors possess immunosuppressive properties that confer resistance to immune-destruction. For instance, because tumors are not foreign and tumor antigens thus represent a form of self-antigen, T cell tolerance mechanisms that evolved to prevent autoimmunity have the undesirable effect of dampening tumor immunity.We have developed transgenic mouse models to study how T cell tolerance is established to self-antigens expressed on both healthy tissues as well as on prostate tumors, and how these tolerogenic processes can be reversed to enhance tumor immunity. In collaboration with Dr. Anthony Vella (Department of Immunology, UCHC) we have been studying how agonist antibodies to the costimulatory molecules CD134 (OX-40) and CD137 (4-1BB) reverse this tolerogenic process to program CD4 and CD8 T cells to differentiate into effector T cells with anti-tumor potential. We are currently working on the following projects:CD134 plus CD137 dual costimulation programs CD4 T cells to differentiate into cytotoxic killers. CD4 T cells normally help other immune cells such as B cells and CD8 T cells to function optimally. We unexpectedly found that CD134 plus CD137 dual costimulation programs CD4 T cells to develop cytotoxic capacity (a function classically associated with CD8+ CTL). Further, these cytotoxic CD4 T cells can directly target tumors, suggesting that dual costimulation therapy may be effective in preventing the outgrowth of CD8+ CTL-resistant tumors (a common problem associated with T cell-based cancer therapies). We are currently analyzing the cellular and molecular mechanisms by which dual costimulation programs this “non-classical” but therapeutically useful CD4 T cell differentiation pathway.Helping CD8 T cells to attack tumors. We have found that distinct CD4 helper-elicited cytokines work both cooperatively and antagonistically to program distinct facets of CD8 T cell responsiveness and effector function. Current efforts are aimed towards furthering our mechanistic understanding of these helper pathways, and how they can be harnessed to augment tumor immunity.
Accepting Lab Rotation Students: Spring 2 Block 2025
1. Examine how the IL-2 signaling pathway and the T-box transcription factor Eomesodermin cooperate to program epigenetic remodeling and transcription of genes encoding cytotoxic molecules in dual-costimulated CD4 T cells.2. Analyze the functional properties of regulatory T cells (Tregs) that have been induced to express cytotoxic molecules.3. Examine how CD4 helper-elicited cytokines act cooperatively to induce cytotoxic molecules but antagonistically to regulate IL-2 receptor expression in CD8 T cells.4. Assess the therapeutic potential of dual-costimulated CD4 and CD8 T cells in various tumor models.
Journal Articles
-
Autoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation.
Science (New York, N.Y.) 2024 Sep;385(6714):eadj1979
-
High glucose promotes regulatory T cell differentiation.
PloS one 2023 Jan;18(2):e0280916
-
Cancer Immunology and Immunotherapy: From Defining Basic Immunology to Leading the Fight Against Cancer.
Immunological investigations 2022 Nov;1-5
-
Lymphocyte Activation Gene-3 Regulates Dendritic Cell Metabolic Programing and T Cell Priming Function.
Journal of immunology (Baltimore, Md. : 1950) 2021 Sep;
-
GRK2 enforces androgen receptor dependence in the prostate and prostate tumors.
Oncogene 2020 Jan;
-
IL-17 inhibits CXCL9/10-mediated recruitment of CD8+ cytotoxic T cells and regulatory T cells to colorectal tumors.
Journal for immunotherapy of cancer 2019 Nov;7(1):324
-
A mathematical model of combined CD8 T cell costimulation by 4-1BB (CD137) and OX40 (CD134) receptors.
Scientific reports 2019 Jul;9(1):10862
-
Costimulation Induces CD4 T Cell Antitumor Immunity via an Innate-like Mechanism.
Cell reports 2019 Apr;27(5):1434-1445.e3
-
An Immunotherapeutic CD137 Agonist Releases Eomesodermin from ThPOK Repression in CD4 T Cells.
Journal of immunology (Baltimore, Md. : 1950) 2018 Feb;200(4):1513-1526
-
A novel biologic platform elicits profound T cell costimulatory activity and antitumor immunity in mice.
Cancer immunology, immunotherapy : CII 2018 Jan;67605-613
-
Cytokines and metabolic factors regulate tumoricidal T-cell function during cancer immunotherapy.
Immunotherapy 2017 Jan;9(1):71-82
-
Enhancing the safety of antibody-based immunomodulatory cancer therapy without compromising therapeutic benefit: Can we have our cake and eat it too?
Expert opinion on biological therapy 2016 Feb;16655-74
-
Costimulation Endows Immunotherapeutic CD8 T Cells with IL-36 Responsiveness during Aerobic Glycolysis.
Journal of immunology (Baltimore, Md. : 1950) 2015 Nov;196124-34
-
Tumor-Unrelated CD4 T Cell Help Augments CD134 Plus CD137 Dual Costimulation Tumor Therapy.
Journal of immunology (Baltimore, Md. : 1950) 2015 Nov;1955816-26
-
Striving for synergy: how to improve cancer immunotherapy through multiple agonist costimulation.
Immunotherapy 2013 Dec;5(12):1271-3
-
CD134/CD137 dual costimulation-elicited IFN-γ maximizes effector T-cell function but limits Treg expansion.
Immunology and cell biology 2013 Feb;91(2):173-83
-
Presensitizing with a Toll-like receptor 3 ligand impairs CD8 T-cell effector differentiation and IL-33 responsiveness.
Proceedings of the National Academy of Sciences of the United States of America 2012 Jun;109(26):10486-91
-
CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation.
Journal of immunology (Baltimore, Md. : 1950) 2011 Oct;187(7):3555-64
-
Tc17 CD8 T cells: functional plasticity and subset diversity.
Journal of immunology (Baltimore, Md. : 1950) 2009 Dec;183(11):7161-8
-
The E3 ubiquitin ligase Cbl-b regulates expansion but not functional activity of self-reactive CD4 T cells.
Journal of immunology (Baltimore, Md. : 1950) 2009 Oct;183(8):4975-83
-
SAAG-4 is a novel mosquito salivary protein that programmes host CD4 T cells to express IL-4.
Parasite immunology 2009 Jun;31(6):287-95
-
Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells.
Journal of immunology (Baltimore, Md. : 1950) 2009 Apr;182(8):4675-85
-
A novel sphingomyelinase-like enzyme in Ixodes scapularis tick saliva drives host CD4 T cells to express IL-4.
Parasite immunology 2009 Apr;31(4):210-9
-
In vitro and in vivo differentiated effector CD8 T cells display divergent histone acetylation patterns within the Ifng locus.
Immunology letters 2009 Feb;122(2):214-8
-
Blood feeding by the Rocky Mountain spotted fever vector, Dermacentor andersoni, induces interleukin-4 expression by cognate antigen responding CD4<sup>+</sup> T cells
Parasites and Vectors 2009 Jan;2(1):
-
The IKK-neutralizing compound Bay11 kills supereffector CD8 T cells by altering caspase-dependent activation-induced cell death.
Journal of leukocyte biology 2009 Jan;85(1):175-85
-
Self-antigen prevents CD8 T cell effector differentiation by CD134 and CD137 dual costimulation.
Journal of immunology (Baltimore, Md. : 1950) 2008 Dec;181(11):7728-37
-
Histone acetylation at the Ifng promoter in tolerized CD4 cells is associated with increased IFN-gamma expression during subsequent immunization to the same antigen.
Journal of immunology (Baltimore, Md. : 1950) 2007 Nov;179(9):5669-77
-
Feeding by the tick, Ixodes scapularis, causes CD4(+) T cells responding to cognate antigen to develop the capacity to express IL-4.
Parasite immunology 2007 Oct;29(10):485-99
-
Steady state dendritic cells present parenchymal self-antigen and contribute to, but are not essential for, tolerization of naive and Th1 effector CD4 cells.
Journal of immunology (Baltimore, Md. : 1950) 2007 Aug;179(3):1524-31
-
Dendritic cells program non-immunogenic prostate-specific T cell responses beginning at early stages of prostate tumorigenesis.
The Prostate 2007 Apr;67(5):536-46
-
Cutting edge: Paracrine, but not autocrine, IL-2 signaling is sustained during early antiviral CD4 T cell response.
Journal of immunology (Baltimore, Md. : 1950) 2006 Oct;177(7):4257-61
-
T-bet down-modulation in tolerized Th1 effector CD4 cells confers a TCR-distal signaling defect that selectively impairs IFN-gamma expression.
Journal of immunology (Baltimore, Md. : 1950) 2006 Jan;176(2):1036-45
-
Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen.
Cancer cell 2005 Mar;7(3):239-49
-
Peripheral Tolerization of Effector and Memory T Cells: Implications for Autoimmunity and Tumor-Immunity.
Current immunology reviews 2005 Jan;1(1):21-28
-
Glycoprotein 96 can chaperone both MHC class I- and class II-restricted epitopes for in vivo presentation, but selectively primes CD8+ T cell effector function.
Journal of immunology (Baltimore, Md. : 1950) 2004 May;172(10):6087-92
-
In vivo cyclophosphamide and IL-2 treatment impedes self-antigen-induced effector CD4 cell tolerization: implications for adoptive immunotherapy.
Journal of immunology (Baltimore, Md. : 1950) 2004 May;172(9):5338-45
-
Effector CD4 cell tolerization is mediated through functional inactivation and involves preferential impairment of TNF-alpha and IFN-gamma expression potentials.
Cellular immunology 2003 Aug;224(2):114-21
-
CD4+ T cells pass through an effector phase during the process of in vivo tolerance induction.
Journal of immunology (Baltimore, Md. : 1950) 2003 Apr;170(8):3945-53
-
Effector CD4 cells are tolerized upon exposure to parenchymal self-antigen.
Journal of immunology (Baltimore, Md. : 1950) 2002 Oct;169(7):3622-9
-
CD4 cell priming and tolerization are differentially programmed by APCs upon initial engagement.
Journal of immunology (Baltimore, Md. : 1950) 2002 Jun;168(11):5573-81
-
In vivo CD4+ T cell tolerance induction versus priming is independent of the rate and number of cell divisions.
Journal of immunology (Baltimore, Md. : 1950) 2000 Jan;164(2):649-55
-
CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells.
The Journal of experimental medicine 1998 May;187(10):1555-64
-
Development and characterization of a cytokine-secreting pancreatic adenocarcinoma vaccine from primary tumors for use in clinical trials.
The cancer journal from Scientific American 1998 Jan;4(3):194-203
-
Specific steroid response from a nonspecific DNA element.
The Journal of steroid biochemistry and molecular biology 1994 Jun;49(4-6):251-5
-
The stringency and magnitude of androgen-specific gene activation are combinatorial functions of receptor and nonreceptor binding site sequences.
Molecular and cellular biology 1993 Oct;13(10):6326-35
-
Androgen-specific gene activation via a consensus glucocorticoid response element is determined by interaction with nonreceptor factors.
Proceedings of the National Academy of Sciences of the United States of America 1992 Dec;89(24):11660-3
-
Multiple components of a complex androgen-dependent enhancer.
Molecular endocrinology (Baltimore, Md.) 1991 Nov;5(11):1587-96
-
Aging and chronic estradiol exposure impair estradiol-induced cornification but not proliferation of vaginal epithelium in C57BL/6J mice.
Biology of reproduction 1988 Feb;38(1):175-82
Book Chapters
-
Mechanisms of Tumor-Associated T-Cell Tolerance
Tumor-Induced Immune Suppression 2008 Jan;7-27
Editorials
-
Letter from the Editor: 2022.
Immunological investigations 2022 Nov;51(8):2123-2127
Letters
-
Letter from the Editor and Introduction to the 2023 Thematic Issue.
Immunological investigations 2024 Feb;1-5
-
Letter from the Editor: 2021.
Immunological investigations 2021 Oct;50(7):735-739
Notes
-
Timing of vaccine therapy may be important in prostate cancer
Cancer Biology and Therapy 2005 Jan;4(4):
Reviews
-
Macrophage polarization and meta-inflammation.
Translational research : the journal of laboratory and clinical medicine 2018 Jan;19129-44
-
Mechanisms of T cell tolerance and suppression in cancer mediated by tumor-associated antigens and hormones.
Current cancer drug targets 2007 Feb;7(1):3-14