Research

Aging and autoimmunity: Down syndrome gives a master class

People with Down syndrome show clinical features associated with advanced immune aging, including increased autoimmunity (up to 100x!), impaired vaccine response and increased susceptibility to infections including influenza and COVID-19. We recently built a uniquely detailed atlas of the immune system in people with Down syndrome and found that the immune system of a person with Down syndrome resembles that of a typical individual up to 17 years older! These efforts also demonstrated how Down syndrome can reveal novel programs of immune dysregulation in other autoimmune diseases like type 1 diabetes. We are working to understand how we can use immune age to better guide clinical care, and how trisomy 21 drives advanced immune aging, so that we can design therapies to reverse immune aging in people with, and ultimately without, Down syndrome. This work is in close collaboration with Dr. Rebecca Partridge and the regional Down syndrome community. Learn more about our Down syndrome biorepository.

The Druggable Treg Genome: DYRK1A

We pioneered a high-throughput unbiased discovery effort in primary T cells to discover novel small molecules that enhance Treg differentiation. This approach is a powerful complement to standard genetic techniques for at least two reason:

Mechanistic studies of our small molecule enhancers can identify novel biology. In particular, we identified the kinases DYRK1A and CDK8 as a novel druggable regulator of Treg differentiation. Inhibition of DYRK1A or CDK8 shows great promise in reducing inflammation in model systems. We are pursuing mechanistic studies to highlight additional druggable targets and corresponding precision medicine approaches, while collaborating to develop better inhibitors with better pharmacological properties.

Novel regulators of Th differentiation: DYRK1A and CDK8

Presentation by Bernard Khor, MD, PhD, at University of Washington Laboratory Medicine Grand Rounds

Community presentation: Immune aging in people with DS

Paying back and forward to the community is a priority for us. We shared our recently published findings with LifeSPAN, a group dedicated to improving the lives of people with disabilities including Down syndrome - link here.

Recent publications, selected