Dr. Yan received his Ph.D. in 2006 from University of Texas at Austin. After completing postdoctoral work at Harvard Medical School, Dr. Yan joined UT Southwestern Department of Internal Medicine and Department of Microbiology in January 2011.

Research in our lab focuses on understanding how HIV exploits host factors to evade innate immune detection. Viral nucleic acids introduced into cells or synthesized during infection trigger cytosolic sensors of innate immunity to produce antiviral cytokines, such as type I interferons (IFN). Some viruses evade immune sensing. Although HIV introduces genomic RNA and then generates a variety of DNA products in the cytosol through reverse transcription, HIV infection of T cells and macrophages does not trip these alarms. How HIV avoids activating innate immune sensors of foreign nucleic acids is unknown. Few copies of HIV DNA integrate in a cell during infection, leaving behind some HIV DNA in the cytosol. Unintegrated HIV DNA is believed to be cleared by host enzymes. We recently found that the cytosolic exonuclease TREX1 suppressed interferon triggered by HIV. We are interested in characterizing mechanism(s) by which the innate immune recognition of HIV is regulated. We hope to develop novel antiretroviral therapeutics that is based on enhancing innate immunity.

Another area of interest in our lab is to understand the pathogenesis of human autoimmune diseases. Mutations in human TREX1 gene are associated with Aicardi-Goutieres syndrome (AGS), a severe neurological brain disease often found in infant and young children, familial chilblain lupus (FCL) and systemic lupus erythematosus (SLE). Trex1−/− mice develop autoimmune noninfectious inflammatory myocarditis and often die of heart failure. Studies of Trex1−/− mice suggested that DNA derived from endogenous retroelements maybe the underlying cause of autoimmunity. Endogenous retroelements share many similarities with retroviruses in their life cycle, especially reverse transcription. Retroelements comprise nearly half of the human genome. We are interested in investigating how our cells regulate these mobile genetic elements and what are the molecular and clinical consequences when things go awry. We hope to develop useful biomarkers and treatments for related human autoimmune diseases.

The long-term goals of our lab are to understand the innate strategy of nucleic acid recognition in the cell, similarities in recognition of retroviruses and retroelements, and fundamental principles of self vs non-self discrimination.