Assistant Professor of Pediatrics
- AB, Harvard University, 1995
- AM, Harvard University, 1995
- MD, Harvard Medical School, 2000
- Residency in Pediatrics, University of California, San Francisco, 2000-2003
- Chief Residency in Pediatrics, University of California, San Francisco, 2003-2004
- Fellowship in Pediatric Endocrinology, University of California, San Francisco, 2004-2007
- Pediatric Scientist Development Program, 2005-2008
- Central Tolerance
- Therapies for Inducing Tolerance
- Autoimmune Polyendocrinopathy Syndrome Type 1
- Chronic Inflammatory Demyelinating Polyneuropathy
- Type 1 Diabetes
- Turner Syndrome
Autoimmune diseases are a significant health problem, affecting 5-10% of the population. Despite its prevalence, however, the pathophysiology of most autoimmune diseases has been difficult to unravel, partly because most diseases have a complex genetic inheritance. Most autoimmune diseases have multiple contributing genetic loci, and many of these genetic loci have subtle effects on disease manifestation, making for complex systems to study. An exception to this are the rare monogenic syndromes of autoimmunity, such as Autoimmune Polyendocrinopathy Syndrome (APS) Type 1, also known as APECED. These syndromes are due to single gene defects that have a large impact on disease manifestation, thus making for a much simpler system to study.
APS Type 1 has classically been described as an autosomal recessive condition and is due to mutations in the Autoimmune Regulator (Aire) gene. The syndrome is characterized by autoimmunity in multiple different organs, including the parathyroid gland and the adrenal gland. We became interested in a particular dominant mutation in Aire (G228W) that seems to result in an atypical clinical picture. Like people, knockin mice harboring the G228W mutation also develop autoimmunity in a distinct set of organs, including the peripheral nerves and pancreatic islets. Our current research focus is to:
- Utilize this mouse model to understand the disease mechanisms underlying autoimmune peripheral neuropathy and autoimmune diabetes.
- Utilize this mouse model to test novel therapies to prevent and reverse autoimmunity.
- Understand how this point mutation disrupts the normal function of the Aire gene.