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Randolph J. Noelle, PhD

Emeritus Professor of Microbiology and Immunology

Microbiology and Immunology

Albany Medical College, PHD 1980
SUNY - Stony Brook,
BS 1974

Dr. Noelle was a post-doctoral fellow at the University of Texas Health Science Center at Dallas from 1980-1984
and in 1984, he joined the faculty of Dartmouth Medical School as an Assistant Professor. In 1995, he was promoted to Professor of Microbiology and Immunology.

Project Cork


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Contact Information

Borwell Research Building
1 Medical Center Drive
HB 7556
Lebanon NH 03755

Phone: 603-653-9908
Fax: 603-653-9900
Email: Randolph.J.Noelle@Dartmouth.Edu

Professional Interests

In 1991, Professor Noelle's laboratory identified a novel membrane protein expressed on helper T lymphocytes (Th), CD154. The receptor for CD154 is CD40. CD40 is expressed on B lymphocytes and antigen-presenting cells. This ligand-receptor pair plays a central role in the control of antibody- and cell-mediated immunity. Intervention in CD154-CD40 interactions (by genetic deletion or antibody-blockade) can block a wide spectrum of immune and autoimmune responses as well as transplantation rejection. As a result, the laboratory has focused on four areas of immunobiology that are relevant to CD40 function.

Regulatory T cell biology:

Peripheral tolerance in cancer and in graft tolerance is sustained by regulatory T cells. Our laboratory studies the network of cells (mast cells, DCs) and factors (PD-L1, Retinoic acid) that control their activities.

B cell memory and plasma cell development:

Our goals are to understand the factors that control the remarkable longevity of plasma cells and memory B cells in mice. Studies using global gene analysis have and will lead to novel genetic targets that allow us to understand the mechanisms that allow the persistence of these cells in humans for decades.

Immune tolerance in transplantation:

Perhaps the most impressive activity of ±CD154 is its ability to block the rejection of fully allogeneic skin, heart, kidney and islet allografts in mice, and in some of these cases in monkeys. Exciting new insights into how ±CD154 induces peripheral T cell tolerance and long-lived graft acceptance have emerged from these studies. The impact of ±CD154 on T cell anergy, regulatory T cell function, and dendritic cell biology are all elements in engendering permanent allograft survival.

Recently we have shown that retinoic acid can exert profound effects on Tregs and are now deeply involved in how this dietary supplement controls T cell fate.

Cancer vaccines:

CD40 is such a powerful activator of the immune system, we have exploited it as a target in producing a new generation of molecularly defined immune adjuvants. Using CD40 agonists and other pro-inflammatory mediators we are engineering adjuvant platforms that can induce profound levels of cell-mediated immunity. Our interest lie in both the practical development of these novel platforms and the basic science behind how they work.

Translational Immunotherapy:

Our laboratory has been involved with numerous translational efforts in the areas of antibody-based immunotherapy and cellular vaccines for cancer. We have produced monoclonal antibodies that have entered clinical trials at Dartmouth and around the world, and we have played an active role in the development of clinical trials for cellular vaccines for cancer. We continue to aggressively translate basic scientific discoveries into the clinic and measure the impact of these interventions using highly sophisticated measurements of human immunity.

Selected Publications


Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights.
Noelle RJ, Lines JL, Lewis LD, Martell RE, Guillaudeux T, Lee SW, Mahoney KM, Vesely MD, Boyd-Kirkup J, Nambiar DK, Scott AM
Front Oncol. 2023;13:1225081. doi: 10.3389/fonc.2023.1225081. Epub 2023 Sep 15.
PMID: 37795437

VISTA expression and patient selection for immune-based anticancer therapy.
Martin AS, Molloy M, Ugolkov A, von Roemeling RW, Noelle RJ, Lewis LD, Johnson M, Radvanyi L, Martell RE
Front Immunol. 2023;14:1086102. doi: 10.3389/fimmu.2023.1086102. Epub 2023 Feb 20.
PMID: 36891296

VISTA Targeting of T-cell Quiescence and Myeloid Suppression Overcomes Adaptive Resistance.
Schaafsma E, Croteau W, ElTanbouly M, Nowak EC, Smits NC, Deng J, Sarde A, Webber CA, Rabadi D, Cheng C, Noelle R, Lines JL
Cancer Immunol Res. 2023 Jan 3;11(1):38-55. doi: 10.1158/2326-6066.CIR-22-0116.
PMID: 36260656

CD49b Targeting Inhibits Tumor Growth and Boosts Anti-tumor Immunity.
Contreras-Kallens P, Galvez-Jiron F, De Solminihac J, Elhusseiny A, Gonzalez-Arriagada WA, Alcayaga-Miranda F, Noelle RJ, Pino-Lagos K
Front Oncol. 2022;12:928498. doi: 10.3389/fonc.2022.928498. Epub 2022 Jul 4.
PMID: 35860556

Retinoic acid signaling acts as a rheostat to balance Treg function.
Thangavelu G, Andrejeva G, Bolivar-Wagers S, Jin S, Zaiken MC, Loschi M, Aguilar EG, Furlan SN, Brown CC, Lee YC, Hyman CM, Feser CJ, Panoskaltsis-Mortari A, Hippen KL, MacDonald KP, Murphy WJ, Maillard I, Hill GR, Munn DH, Zeiser R, Kean LS, Rathmell JC, Chi H, Noelle RJ, Blazar BR
Cell Mol Immunol. 2022 Jul;19(7):820-833. doi: 10.1038/s41423-022-00869-y. Epub 2022 May 17.
PMID: 35581350

Safety and Immune Effects of Blocking CD40 Ligand in Multiple Sclerosis.
Fadul CE, Mao-Draayer Y, Ryan KA, Noelle RJ, Wishart HA, Channon JY, Kasper IR, Oliver B, Mielcarz DW, Kasper LH
Neurol Neuroimmunol Neuroinflamm. 2021 Nov;8(6) doi: 10.1212/NXI.0000000000001096. Epub 2021 Oct 15.
PMID: 34654708

VISTA regulates microglia homeostasis and myelin phagocytosis, and is associated with MS lesion pathology.
Borggrewe M, Kooistra SM, Wesseling EM, Gierschek FL, Brummer ML, Nowak EC, Medeiros-Furquim T, Otto TA, Lee SW, Noelle RJ, Eggen BJL, Laman JD
Acta Neuropathol Commun. 2021 May 18;9(1):91. doi: 10.1186/s40478-021-01186-7. Epub 2021 May 18.
PMID: 34006329

PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype.
Fanelli G, Romano M, Nova-Lamperti E, Werner Sunderland M, Nerviani A, Scotta C, Bombardieri M, Quezada SA, Sacks SH, Noelle RJ, Pitzalis C, Lechler RI, Lombardi G, Becker PD
PLoS Biol. 2021 Apr;19(4):e3001199. doi: 10.1371/journal.pbio.3001199. Epub 2021 Apr 26.
PMID: 33901179

VISTA: A Target to Manage the Innate Cytokine Storm.
ElTanbouly MA, Zhao Y, Schaafsma E, Burns CM, Mabaera R, Cheng C, Noelle RJ
Front Immunol. 2020;11:595950. doi: 10.3389/fimmu.2020.595950. Epub 2021 Feb 11.
PMID: 33643285

VISTA Re-programs Macrophage Biology Through the Combined Regulation of Tolerance and Anti-inflammatory Pathways.
ElTanbouly MA, Schaafsma E, Smits NC, Shah P, Cheng C, Burns C, Blazar BR, Noelle RJ, Mabaera R
Front Immunol. 2020;11:580187. doi: 10.3389/fimmu.2020.580187. Epub 2020 Oct 15.
PMID: 33178206

View more publications on PubMed