Identifying triggers for autoimmunity in type 1 diabetes

Project title: The Role of Hybrid Insulin Peptides in the Development of Type 1 Diabetes.
Institution: University of Colorado Denver
Pathway project publications: 3
Promoted to Tenure Track Assistant Professor Position in 2017

Major accomplishments:

We found that diabetes-inducing T cells, isolated from diabetic mice, recognize antigens formed by cross-linking of insulin fragments to other protein fragments (peptides). The resulting hybrid insulin peptides (HIPs) are antigenic for T cells and can be detected by mass spectrometry in beta cell extracts. HIPs contain new protein sequences that are not encoded in our genome and the existence of HIPs provides a plausible explanation on how the immune system gets tricked into attacking the insulin producing beta cells leading to the development of type 1 diabetes. This paradigm-changing discovery was published in the journal Science last year. To date we verified that T cells, isolated from residual pancreatic islets of type 1 diabetes organ donors target several unique HIPs. For instance, we identified one distinct HIP that is recognized by T cells isolated from two different organ donors. This indicates that certain HIPs may be universal antigen targets in type 1 diabetes. Furthermore, we identified three additional T cells isolated from various organ donors that target different HIPs. We also generated various HIP antigen libraries that assist us in our ongoing search to identify additional HIPs that are targeted by autoreactive T cells that play a role in the development of type 1 diabetes.

Impact statement:

This year will mark my 30th anniversary living with type 1 diabetes. This personal affliction put me on the path to understand what initiates this life-altering disease. I believe that if we understand the triggers that lead to the development of type 1 diabetes, we can work on methods to prevent and undo it. When I entered the fields of life sciences, I quickly realized that it is highly competitive and many outstanding researchers spend vast amounts of time competing for the decreasing amounts of available research funds.

The Pathway award provided me not only with funding to spend more time in the lab, but also with intimate connections to experts in the field of diabetes research. The remarkable group of Pathway mentors is a great portal to diabetes researchers as well as diabetes resources. My Pathway mentor has been extremely helpful in guiding me to advance my career and to become more proficient in reaching my goals. The Pathway award helped me move into a tenure track faculty position at the University of Colorado. I am now the principal investigator in a new laboratory with a highly sophisticated mass spectrometer that I will use to probe the insulin producing beta cells to characterize the relevant antigens for type 1 diabetes and other diseases.

I am grateful to the Pathway program for accelerating my career and helping me address the questions that I consider essential to find a cure for type 1 diabetes.