We can better predict and treat Type 1 diabetes (T1D) by studying its genetic forms. While most people living with T1D are not closely related to anyone else with the disease, approximately 10% have an affected parent, sibling, or child. This suggests a strong single-gene, or monogenic, driver in these individuals. Genetic sequencing now allows us to identify culprit mutations and offer targeted therapies – an example of precision medicine at its finest. Examining these rare families is also likely to reveal underlying mechanisms and druggable pathways applicable to all people with T1D. 

A collaborative group of investigators at the University of California, San Francisco and University of Chicago has been recruiting families with evidence of monogenic T1D and sequencing their DNA. We have now sequenced over 200 families and identified at least 7 candidate genes. With the support of this Diabetes Research Connection grant, I plan to focus on a few main candidates.

We hypothesize that these genes play a crucial role in the immune system, specifically in an organ called the thymus. The thymus is a small gland in the chest that teaches important immune cells called T-cells to protect the body against infections. To do this, T-cells must learn to properly differentiate between foreign and self so that they only kill invaders. In autoimmune diseases like T1D, this process goes awry, and T-cells instead attack the body’s own pancreatic beta cells.

Our multidisciplinary team consists of scientists with expertise in immunology, genetics, and endocrinology. As a first step to investigate these genes, we plan to study their expression in human cell lines. We will then look at their impact on the rate of diabetes development, thymic cell environment, and islet inflammation in a T1D animal model. The results are expected to reveal the role of our identified candidate genes in the development of T1D.

As someone who has lived with T1D for over 20 years, I understand first-hand the daily struggles of managing this chronic disease. I am also a physician and see T1D patients both in the clinic and hospital who suffer from diabetes distress and complications from their disease. Overall, the goal of my research is to improve the quality of life for individuals with T1D. I envision our work may lead to the reversal of T1D in patients with certain mutations who receive targeted therapy, and eventually prevention of the disease altogether.