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Randolph J. Noelle, PhD

Title(s):
Professor of Microbiology and Immunology

Department(s):
Microbiology and Immunology

Education:
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.

Programs:
Project Cork

Websites:
http://dms.dartmouth.edu/microbio/
http://dms.dartmouth.edu/immuno/
http://www.dartmouth.edu/~mcb/
http://dms.dartmouth.edu/ncd/
http://dms.dartmouth.edu/COBRE/

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:

 

Bolstering the Number and Function of HSV-1-Specific CD8<sup>+</sup> Effector Memory T Cells and Tissue-Resident Memory T Cells in Latently Infected Trigeminal Ganglia Reduces Recurrent Ocular Herpes Infection and Disease.
Khan AA, Srivastava R, Chentoufi AA, Kritzer E, Chilukuri S, Garg S, Yu DC, Vahed H, Huang L, Syed SA, Furness JN, Tran TT, Anthony NB, McLaren CE, Sidney J, Sette A, Noelle RJ, BenMohamed L
J Immunol. 2017 May 24; pii: 1700145. doi: 10.4049/jimmunol.1700145. Epub 2017 May 24.
PMID: 28539429

Immunoregulatory functions of VISTA.
Nowak EC, Lines JL, Varn FS, Deng J, Sarde A, Mabaera R, Kuta A, Le Mercier I, Cheng C, Noelle RJ
Immunol Rev. 2017 Mar;276(1):66-79. doi: 10.1111/imr.12525.
PMID: 28258694

Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response.
Marks E, Ortiz C, Pantazi E, Bailey CS, Lord GM, Waldschmidt TJ, Noelle RJ, Elgueta R
Front Immunol. 2016;7:643. doi: 10.3389/fimmu.2016.00643. Epub 2016 Dec 23.
PMID: 28066447

A New VISTA on combination therapy for negative checkpoint regulator blockade.
Deng J, Le Mercier I, Kuta A, Noelle RJ
J Immunother Cancer. 2016;4:86. doi: 10.1186/s40425-016-0190-5. Epub 2016 Dec 20.
PMID: 28031817

VISTA Deficiency Accelerates the Development of Fatal Murine Lupus Nephritis.
Ceeraz S, Sergent PA, Plummer SF, Schned AR, Pechenick D, Burns CM, Noelle RJ
Arthritis Rheumatol. 2017 Apr;69(4):814-825. doi: 10.1002/art.40020.
PMID: 27992697

Endothelial Plasmalemma Vesicle-Associated Protein Regulates the Homeostasis of Splenic Immature B Cells and B-1 B Cells.
Elgueta R, Tse D, Deharvengt SJ, Luciano MR, Carriere C, Noelle RJ, Stan RV
J Immunol. 2016 Nov 15;197(10):3970-3981. Epub 2016 Oct 14.
PMID: 27742829

IL-33 enhances retinoic acid signaling on CD4+ T cells.
Gajardo T, Perez F, Terraza C, Campos-Mora M, Noelle RJ, Pino-Lagos K
Cytokine. 2016 Sep;85:120-2. doi: 10.1016/j.cyto.2016.06.016. Epub 2016 Jun 17.
PMID: 27322964

Treatment with retinoid X receptor agonist IRX4204 ameliorates experimental autoimmune encephalomyelitis.
Chandraratna RA, Noelle RJ, Nowak EC
Am J Transl Res. 2016;8(2):1016-26. Epub 2016 Feb 15.
PMID: 27158387

Platelet CD40 Exacerbates Atherosclerosis by Transcellular Activation of Endothelial Cells and Leukocytes.
Gerdes N, Seijkens T, Lievens D, Kuijpers MJ, Winkels H, Projahn D, Hartwig H, Beckers L, Megens RT, Boon L, Noelle RJ, Soehnlein O, Heemskerk JW, Weber C, Lutgens E
Arterioscler Thromb Vasc Biol. 2016 Mar;36(3):482-90. doi: 10.1161/ATVBAHA.115.307074. Epub 2016 Jan 28.
PMID: 26821950

Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators.
Le Mercier I, Lines JL, Noelle RJ
Front Immunol. 2015;6:418. doi: 10.3389/fimmu.2015.00418. Epub 2015 Aug 21.
PMID: 26347741