The onset of autoimmunity is a complex and incompletely understood process, but it well established that, in genetically susceptible individuals, specific environmental and hormonal conditions alter regulatory control of the immune system, resulting in chronic inflammation and the loss of self-tolerance. Genetic understanding of clinically and molecularly complex autoimmune diseases empowers therapeutic discoveries by improving clinical trial design and precision diagnostics.  SLE lags behind that of other complex genetic diseases in FDA-approved diagnostic and treatment options, emphasizing an urgent need for such discoveries.

I have dedicated my research career to define the genetic susceptibility of lupus and understanding how it disrupts immune system regulation to drive the autoantibody production and systemic inflammation that results in tissue damage and organ failure.  Over the past two decades, our work has contributed significantly to research establishing SLE as a complex genetic disease.  We have successfully identified and functionally characterized SLE risk alleles positioned in noncoding regulatory regions spanning the TNFAIP3, UBE2L3, and TNIP1 risk loci that modulate transcription factor recruitment/binding, epigenome modifications, and/or chromatin-chromatin interactions that alter the expression of genes implicated in SLE pathology.

Our current research leverages innovative high-throughput and multiomic sequencing approaches and computational prediction models to create a high-throughput approach to identify which of the tens of thousands of candidate causal variants spanning the 330 genome-wide significant SLE risk loci impact signaling pathways in human primary B and T cells to drive disease mechanisms.  By pinpointing the variants and regulatory mechanisms that drive autoimmunity, this research will help bridge the gap between genetic risk and disease mechanisms, thereby empowering genetically informed therapeutic development for SLE in the future.