Type 1 diabetes (T1D) is an autoimmune disease affecting approximately 1 in 250 individuals in the United States. While T1D is the most common pediatric autoimmune disease, there is no cure. Instead, the only treatment is daily exogenous insulin replacement therapy. But even with this intervention, many T1D patients develop secondary complications such as heart disease, blindness, peripheral neuropathy and renal failure.
With my research, I work to better understand the mechanism by which immune tolerance is maintained, broken and reestablished. I focus on two autoimmune diseases, Type 1 diabetes and multiple sclerosis, as well as allograft transplant tolerance in heart transplants. My work will help develop key pre-clinical strategies for controlling auto- and allo-reactive T cells, which will provide better therapies for transplanted organ survival and autoimmune diseases like T1D.
My research interests began while I was working on tumor immunity as a basic immunology graduate student. With my postdoctoral research, I moved into the more specialized area of autoimmunity, a major unmet need at the time. It was there that I developed a strong interest in T-cell biology, immune tolerance and transplantation.
I developed the first T-cell receptor (TCR) transgenic mouse, which carried the rearranged TCR from a T cell known to mediate Type 1 diabetes. This mouse allowed us to study the mechanism of T-cell development, maturation, activation and effector function. My lab was the first to show that T1D is a T-helper type 1 (Th1) autoimmune disease.
Our work also demonstrated that these T-cells were under specific genetic control, and that inheritance of certain genetic regions ultimately controlled the T-cell’s function. My TCR transgenic mouse was critical in identifying a novel subset of autoantigens made by pancreatic beta cells. I also demonstrated that T cells kill beta cells by direct and indirect apoptosis.
Now, we have developed techniques to directly target activated auto- and allo-reactive T cells in T1D, multiple sclerosis and allogenic heart transplant models.
Because of my efforts, I have been honored with the:
I am also chair of the American Diabetes Associations’ Immunology, Immunogenetics and Transplantation Group, and a member of the Henry Kunkel Society and Sigma Xi. Additionally, I actively review diabetes, endocrine and metabolism fellowship applications for the National Institutes of Health.
I am committed to basic research, graduate education, postdoctoral training and career mentoring. When I am not in the lab, I enjoy road cycling, cooking, gardening and the great outdoors.
BS: University of California, Los Angeles, CA, 1984.
PhD: University of California, Los Angeles, CA, 1990.
Post-Doctoral Fellow: Université Louis Pasteur, Strasbourg, France, 1990-1995.
T cells; MHC, beta cell death; islet antigens
Immunology; autoimmunity; type 1 diabetes
Molecular Immunology, Endocrinology, Immunobiology
T cells instruct myeloid cells to produce inflammasome-independent IL-1β and cause autoimmunity. Nature Immunology. 2020; 21:65-74.