Edit Entry

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:

 

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 Sep 29;
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

Le Mercier I, Chen W, Lines JL, Day M, Li J, Sergent P, Noelle RJ, Wang L
VISTA Regulates the Development of Protective Antitumor Immunity.
Cancer Res 2014 Apr 1; 74(7):1933-44
PMID: 24691994

Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O'Connell S, Ceeraz S, Suriawinata AA, Yan S, Ernstoff MS, Noelle R
VISTA is an immune checkpoint molecule for human T cells.
Cancer Res 2014 Apr 1; 74(7):1924-32
PMID: 24691993

Guo Y, Lee YC, Brown C, Zhang W, Usherwood E, Noelle RJ
Dissecting the role of retinoic acid receptor isoforms in the CD8 response to infection.
J Immunol 2014 Apr 1; 192(7):3336-44
PMID: 24610012

Ceeraz S, Nowak EC, Noelle RJ
B7 family checkpoint regulators in immune regulation and disease.
Trends Immunol 2013 Nov; 34(11):556-63
PMID: 23954143

Allie SR, Zhang W, Tsai CY, Noelle RJ, Usherwood EJ
Critical role for all-trans retinoic acid for optimal effector and effector memory CD8 T cell differentiation.
J Immunol 2013 Mar 1; 190(5):2178-87
PMID: 23338237

Stan RV, Tse D, Deharvengt SJ, Smits NC, Xu Y, Luciano MR, McGarry CL, Buitendijk M, Nemani KV, Elgueta R, Kobayashi T, Shipman SL, Moodie KL, Daghlian CP, Ernst PA, Lee HK, Suriawinata AA, Schned AR, Longnecker DS, Fiering SN, Noelle RJ, Gimi B, Shworak NW, Carriere C
The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition.
Dev Cell 2012 Dec 11; 23(6):1203-18
PMID: 23237953

Nowak EC, de Vries VC, Wasiuk A, Ahonen C, Bennett KA, Le Mercier I, Ha DG, Noelle RJ
Tryptophan hydroxylase-1 regulates immune tolerance and inflammation.
J Exp Med 2012 Oct 22; 209(11):2127-35
PMID: 23008335

Guo Y, Pino-Lagos K, Ahonen CA, Bennett KA, Wang J, Napoli JL, Blomhoff R, Sockanathan S, Chandraratna RA, Dmitrovsky E, Turk MJ, Noelle RJ
A retinoic acid--rich tumor microenvironment provides clonal survival cues for tumor-specific CD8(+) T cells.
Cancer Res 2012 Oct 15; 72(20):5230-9
PMID: 22902413