Randolph J. Noelle, PhD
Professor of Microbiology and Immunology
Microbiology and Immunology
Albany Medical College, PHD 1980
SUNY - Stony Brook,
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.
Borwell Research Building
1 Medical Center Drive
Lebanon NH 03755
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 Â±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 Â±CD154 induces peripheral T cell tolerance and long-lived graft acceptance have emerged from these studies. The impact of Â±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.
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.
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.
VISTA: a novel immunotherapy target for normalizing innate and adaptive immunity.
Hypoxia-Induced VISTA Promotes the Suppressive Function of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment.
Dendritic Cell Expression of Retinal Aldehyde Dehydrogenase-2 Controls Graft-versus-Host Disease Lethality.
VISTA expression by microglia decreases during inflammation and is differentially regulated in CNS diseases.
VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival.
VISTA deficiency attenuates antibody-induced arthritis and alters macrophage gene expression in response to simulated immune complexes.
Bolstering the Number and Function of HSV-1-Specific CD8+ Effector Memory T Cells and Tissue-Resident Memory T Cells in Latently Infected Trigeminal Ganglia Reduces Recurrent Ocular Herpes Infection and Disease.
Immunoregulatory functions of VISTA.
Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response.
Functions of CD40 and Its Ligand, gp39 (CD40L).