Our group has an overall focus on immune-mediated diseases, and in particular diseases mediated by altered CD4+ T cell function. We have active research programs in Rheumatoid Arthritis, Psoriasis, Type I Diabetes, Age-Related Macular Degeneration, and Tuberculosis. Our approach is the combination of computational and statistical methods, high-throughput genomic technologies, and systems biology to eludicate the genetic mechanisms of these conditions and their functional implications.

 

Disease Focus.

Rheumatoid Arthritis. Rheumatoid athritis (RA) is an inflammatory polyarthritis affecting up to 1% of the population. We have worked with collaborators to identify the >100 alleles assocaited with rheumatoid arthritis. We have also fine-mapped the MHC locus, which continues to have the largest effect of all RA loci, to individual amino acid sites within the HLA. We are now focused on the role of altered CD4 T cell function in RA pathogenesis.

Type I Diabetes. Type 1 diabetes (T1D) is a highly heritable autoimmune disease that results from T cell-mediated destruction of the insulin-producing pancreatic β cells. The worldwide incidence of T1D has been steadily increasing. Working with collaborators, we are focused on defining the genetic architecture of the MHC in T1D and identifying causal alleles that alter CD4+ T cell function to cause disease.

Tuberculosis. Despite the availability of treatments, tuberculosis (TB) continues to result in >1 million deaths worldwide. The role of CD4+ T cell dysfunction is well known to mediate reactivation of TB, but the specific mechanisms continue to be unclear.

 

 

Functional genomics and Systems Biology of the Immune Cells.

In order to disentangle the role of genetic variation on gene regulation, we are focused on investigating the role of of common disease alleles on gene regulation. We exploit epigenetic modifications throughout the genome, which identify regions critical to active gene regulation. We are also deeply interested in applying bulk and single cell RNA sequencing, to query gene regulation in immunological cell-types. Our group is particularly adept with and heavily employs computational and integrative methods.

 

 

Human Genetics.

Our group has brough the power of human genetics to bear on these and other diseases. We focus on discovering and fine-mapping complex disease loci, and in particular loci for immune mediated diseases. We combine a wide range of genotyping and high-throughput sequencing techniques, with cutting edge statistical methods to pinpoint common and rare disease alleles. Our group has fine-mapped HLA associations for a wide range of diseases, and has identified the genetic architecture of rare varation in age-related macular degeneration.

 

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