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.
Safety and Immune Effects of Blocking CD40 Ligand in Multiple Sclerosis.
VISTA regulates microglia homeostasis and myelin phagocytosis, and is associated with MS lesion pathology.
PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype.
VISTA: A Target to Manage the Innate Cytokine Storm.
VISTA Re-programs Macrophage Biology Through the Combined Regulation of Tolerance and Anti-inflammatory Pathways.
Rethinking peripheral T cell tolerance: checkpoints across a T cell's journey.
Repurposing a novel anti-cancer RXR agonist to attenuate murine acute GVHD and maintain graft-versus-leukemia responses.
Exploring the VISTA of microglia: immune checkpoints in CNS inflammation.
VISTA is a checkpoint regulator for naive T cell quiescence and peripheral tolerance.
Defining the Signature of VISTA on Myeloid Cell Chemokine Responsiveness.