Remi Creusot, PhD
Type 1 diabetes is an autoimmune disease that often manifests itself suddenly and with devastating effects, most commonly in children. Despite our growing understanding of the cause of type 1 diabetes, we still have no cure. Dr. Creusot’s research studies the loss of immunologic self-tolerance to pancreatic beta cells, the process that occurs when the immune system begins to attack the insulin producing cells of the body. A primary focus of his work is to devise ways to reeducate the immune system and restore tolerance. He and his group study how several processes that contribute to the maintenance of immune tolerance are impaired in people with type 1 diabetes. To this end, the lab is developing new therapeutic strategies aimed at restoring immune tolerance and blocking autoimmunity. This research combines work carried out on the bench in the laboratory and translational studies using patient samples and mice with human immune systems.
More specifically, the Creusot lab’s current research interests are:
- Epitope-based immunotherapy of T1D: We evaluate several platforms to deliver customized epitopes in an effort to rebuild immune tolerance to beta-cell antigens. Our approaches include tolerogenic DNA vaccines and mRNA vaccines and engineered antigen-presenting cells (tolerogenic dendritic cells and stromal cells). All of these use the lab’s patented Endotope platform and Soluble antigen arrays (SAgAs) in partnership with the University of Kansas.
- Tolerogenic antigen-presenting cells in T1D: We characterize antigen-presenting cell populations in relevant tissues, such as pancreas-draining lymph nodes from T1D-prone mice and T1D patients to identify possible functional defects and targets for immunotherapy. These populations include poorly studied lymph node stromal cells, which the lab intends to leverage in its efforts to reestablish tolerance.
- Thymic development and reactivity of human diabetogenic T cells: The lab is using state-of-the-art “human immune system” mouse models to study the human T cells that recognize beta-cell antigens in an effort to understand why they are not properly purged or made tolerant to prevent autoreactivity against beta-cells.
Recent Publications
- Postigo-Fernandez J, Farber DL, Creusot RJ*. Phenotypic alterations in pancreatic lymph node stromal cells from human donors with type 1 diabetes and NOD mice. Diabetologia 2019; 62(11): 2040-2051. PMC6812633
- Postigo-Fernandez J, Firdessa-Fite R, Creusot RJ. Preclinical evaluation of a precision medicine approach to DNA vaccination in Type 1 diabetes. PNAS. 2022; in press.
- Firdessa-Fite R, Johnson SN, Leon MA, Khosravi-Maharlooei M, Baker RL, Sestak JO, Berkland C, Creusot RJ. Soluble Antigen Arrays efficiently deliver peptides and arrest spontaneous autoimmune diabetes. Diabetes. 2021; 70(6):1334-1346.
- Li Y, Teteloshvili N, Tan S, Rao S, Han A, Yang YG, Creusot RJ*. Humanized mice reveal new insights into the thymic selection of human autoreactive CD8+ T cells. Frontiers in Immunology. 2019; 10:63.