Michael Waterfield, MD, PhD

Autoimmune disease affects up to 5% of the population and can cause significant morbidity and mortality. Our labs main focus is to understand the basic mechanisms by which immune tolerance is broken in order to identify novel therapeutic targets for the treatment of autoimmune diseases. We utilize a variety of mouse models to study both central tolerance and peripheral tolerance. Central tolerance is the process by which autoreactive T cells are deleted in the thymus through negative selection. We are currently utilizing a variety of novel conditional knockout mice to study the roles of specific proteins in thymic tolerance.

A second area of active research in the lab is the role of effector T cells in autoimmune disease. One subtype of CD4+ effector T cell, termed T helper 17 (Th17) cells have been found to be important in the pathogenesis of multiple autoimmune diseases and Th17 cells have been targeted therapeutically for treatment. We have identified the activating transcription factor 7 interacting protein (ATF7ip) as a novel regulator of Th17 cell differentiation and are currently studying its mechanism of action in Th17 cells and other immune cells.
Education
Fellowship, 06/2011 - Pediatric Rheumatology, University of California, San Francisco
Residency, 06/2008 - Pediatrics, University of California, San Francisco
MD/PhD, 06/2005 - Medicine, Penn State College of Medicine
Websites
Publications
  1. ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8+ T Cell Effector and Memory Responses.
  2. Gene Expression Meta-Analysis Reveals Concordance in Gene Activation, Pathway, and Cell-Type Enrichment in Dermatomyositis Target Tissues.
  3. The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.
  4. Analysis of pulmonary features and treatment approaches in the COPA syndrome.
  5. 007 GILT-mediated antigen processing in thymic epithelial cells diminishes T cell-mediated protection from melanoma through promoting thymic deletion and regulatory T cells.
  6. Identification of a novel cis-regulatory element essential for immune tolerance.
  7. COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis.
  8. Erratum: Corrigendum: The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
  9. The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
  10. Autoimmunity's collateral damage: Immunodeficiency hints at autoreactivity to cytokines.
  11. Clues to immune tolerance: the monogenic autoimmune syndromes.
  12. NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase.