At 39, Remi Creusot, PhD, has already earned a reputation as a visionary immunologist with an expertise in the field of type 1 diabetes (T1D) research. He was recruited by Columbia University in 2012 from Stanford University, where he received his post-doctoral training. At Stanford, Dr. Creusot identified a malfunctioning gene believed to be involved in the progression of T1D. He also developed an approach to treating the disease that works by re-educating T cells susceptible to mediate inappropriate autoimmune responses, by inhibiting or subverting them. This approach involves the use of mRNA to modify certain types of “educator cells” (dendritic cells) to reprogram T cells. Dr. Creusot has successfully implemented this technique to promote immune tolerance and block T1D in mouse models. This strategy can be easily applied, he says, in humans using dendritic cells generated from the blood.
“I find myself at the frontier of a new era of a more personalized medicine, of more cellular-based therapies and treatments that have potential that is far greater than anything you can possibly imagine with conventional drugs,” said Dr. Creusot.
Raised in the small, rural village of Hadol, in France, the youngest of three sons, Dr. Creusot was educated as a biologist at the University of Nancy in the province of Lorraine. He was barely exposed to immunology until half way through a master’s program in microbiology, when he did an internship in an immunology unit of a British pharmaceutical company working on a vaccine project. “That is when I got the spark,” said Dr. Creusot, “that’s when I knew immunology was for me.”
Dr. Creusot explained: “Through my initial work with vaccines, I was able to get a clear understanding of what it takes to instruct T cells to mount an appropriate immune response, in part by enabling groups of T cells to cooperate. Looking at the flip side of the coin, I thought these concepts of regulation could be used to approach autoimmunity, where T cells need to be reprogrammed to stop responding, and ideally, given the ability to propagate ‘do not attack’ instructions among them.”
He received a PhD in Immunology from the University of London and joined a laboratory at Stanford University, well-known for its research contributions on autoimmune diseases and immune tolerance, first as a post-doctoral fellow and then as a research associate. Now an Assistant Professor at Columbia, he has his own laboratory at the Columbia Center for Translational Immunology (CCTI), working closely with the Naomi Berrie Diabetes Center. Today, Dr. Creusot refers to immunology as “my favorite subject. It is enjoyable to work when you love what you’re working on.”
Said Dr. Creusot: “Here at the CCTI, we have Megan Sykes, MD, a renowned immunologist, also working with the Berrie Center. She’s interested in immune tolerance from a transplantation perspective. Her work could be complemented by someone with more basic questions on the origins of the loss of immune tolerance in human T1D and ways to rescue it, and that’s where I fit in.”
At Columbia, Dr. Creusot’s work is two-fold: to improve our understanding of the pathology of T1D and to explore new strategies for treating it. To that end, Dr. Creusot is pursuing work that he originally started at Stanford, where he was part of the team that discovered that the DEAF1 gene becomes functionally impaired during the progression of T1D in both mice and humans.
“We believe that this gene is important for certain types of educator cells to program self-reactive T cells to be harmless or even protective,” said Dr. Creusot. “Although it does not appear to be involved in the initiation of the disease, it is probably important in controlling it.”
Equally important is the ongoing work he does using mRNA to manipulate dendritic cells to reprogram the immune system. “This is the field I believe I can advance,” said Dr. Creusot. “Hopefully, when I get old and look back, we will be using our own cells to re-educate our own immune system in a way that is safe, efficient and cost-effective. That’s what medicine will look like.”
Click here to learn more about the Berrie Center, T1D research, and to support Dr. Creusot's work.