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Randolph J. Noelle, Ph.D.

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

NIH Biosketch:
Noelle_R_BIO_2009-01-30.pdf

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:

 

Pantazi E, Marks E, Stolarczyk E, Lycke N, Noelle RJ, Elgueta R
Cutting Edge: Retinoic Acid Signaling in B Cells Is Essential for Oral Immunization and Microflora Composition.
J Immunol 2015 Aug 15; 195(4):1368-71
PMID: 26163586

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 15; 89(18):9693-8
PMID: 26157131

Chai JG, Ratnasothy K, Bucy RP, Noelle RJ, Lechler R, Lombardi G
Allospecific CD4(+) T cells retain effector function and are actively regulated by Treg cells in the context of transplantation tolerance.
Eur J Immunol 2015 Jul; 45(7):2017-27
PMID: 25944401

Brown CC, Noelle RJ
Seeing through the dark: New insights into the immune regulatory functions of vitamin A.
Eur J Immunol 2015 May; 45(5):1287-95
PMID: 25808452

Brown CC, Esterhazy D, Sarde A, London M, Pullabhatla V, Osma-Garcia I, Al-Bader R, Ortiz C, Elgueta R, Arno M, de Rinaldis E, Mucida D, Lord GM, Noelle RJ
Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
Immunity 2015 Mar 17; 42(3):499-511
PMID: 25769610

Ceeraz S, Nowak EC, Burns CM, Noelle RJ
Immune checkpoint receptors in regulating immune reactivity in rheumatic disease.
Arthritis Res Ther 2014; 16(5):469
PMID: 25606596

Guo Y, Brown C, Ortiz C, Noelle RJ
Leukocyte homing, fate, and function are controlled by retinoic acid.
Physiol Rev 2015 Jan; 95(1):125-48
PMID: 25540140

Elgueta R, Marks E, Nowak E, Menezes S, Benson M, Raman VS, Ortiz C, O'Connell S, Hess H, Lord GM, Noelle R
CCR6-dependent positioning of memory B cells is essential for their ability to mount a recall response to antigen.
J Immunol 2015 Jan 15; 194(2):505-13
PMID: 25505290

Wang L, Le Mercier I, Putra J, Chen W, Liu J, Schenk AD, Nowak EC, Suriawinata AA, Li J, Noelle RJ
Disruption of the immune-checkpoint VISTA gene imparts a proinflammatory phenotype with predisposition to the development of autoimmunity.
Proc Natl Acad Sci U S A 2014 Oct 14; 111(41):14846-51
PMID: 25267631

Lines JL, Sempere LF, Broughton T, Wang L, Noelle R
VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy.
Cancer Immunol Res 2014 Jun; 2(6):510-7
PMID: 24894088