Michael Waterfield, MD, PhD
Associate Professor
Pediatrics
School of Medicine

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.

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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 & Training

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• Fellowship Pediatric Rheumatology University of California, San Francisco 06/2011
• Residency Pediatrics University of California, San Francisco 06/2008
• MD/PhD Medicine Penn State College of Medicine 06/2005

Websites

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• Clinical Profile at UCSF Benioff Children's Hospital (ucsfbenioffchildrens.org)

Grants and Projects

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• Regulation of medullary thymic epithelial cells and thymic central tolerance by Ikaros, NIH, 2022-2027

Publications (16)

Top publication keywords:
AutoimmunityImmunologic MemoryJointsPolyendocrinopathies, AutoimmuneInterleukin-2Th17 CellsRepressor ProteinsCentral ToleranceThymus GlandTranscription FactorsAutoantigensGenetic Diseases, InbornImmune ToleranceReceptors, Interleukin-7CD8-Positive T-Lymphocytes

• A balancing act in the control of self-antigen expression.
  Nature immunology 2024 Waterfield MR, Anderson MS
• Aire in Autoimmunity.
  Annual review of immunology 2024 Miller CN, Waterfield MR, Gardner JM, Anderson MS
• Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance.
  Science immunology 2023 Sin JH, Sucharov J, Kashyap S, Wang Y, Proekt I, Liu X, Parent AV, Gupta A, Kastner P, Chan S, Gardner JM, Ntranos V, Miller CN, Anderson MS, Schjerven H, Waterfield MR
• ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8+ T Cell Effector and Memory Responses.
  Journal of immunology (Baltimore, Md. : 1950) 2022 Sin JH, Kashyap S, Acenas D, Cortez JT, Lee J, Marson A, Matloubian M, Waterfield MR
• Gene Expression Meta-Analysis Reveals Concordance in Gene Activation, Pathway, and Cell-Type Enrichment in Dermatomyositis Target Tissues.
  ACR open rheumatology 2019 Neely J, Rychkov D, Paranjpe M, Waterfield M, Kim S, Sirota M

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• The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.
  The Journal of experimental medicine 2019 Sin JH, Zuckerman C, Cortez JT, Eckalbar WL, Erle DJ, Anderson MS, Waterfield MR
• Analysis of pulmonary features and treatment approaches in the COPA syndrome.
  ERJ open research 2018 Tsui JL, Estrada OA, Deng Z, Wang KM, Law CS, Elicker BM, Jones KD, Dell SD, Gudmundsson G, Hansdottir S, Helfgott SM, Volpi S, Gattorno M, Waterfield MR, Chan AY, Chung SA, Ley B, Shum AK
• 007 GILT-mediated antigen processing in thymic epithelial cells diminishes T cell-mediated protection from melanoma through promoting thymic deletion and regulatory T cells.
  Journal of Investigative Dermatology 2016 M.P. Rausch, T.C. Metzger, M. Waterfield, J. Cortez, M.S. Anderson, K.T. Hastings
• Identification of a novel cis-regulatory element essential for immune tolerance.
  The Journal of experimental medicine 2015 LaFlam TN, Seumois G, Miller CN, Lwin W, Fasano KJ, Waterfield M, Proekt I, Vijayanand P, Anderson MS
• GILT-mediated processing of a self and melanoma antigen in thymic epithelial cells promotes deletion and regulatory T cells (APP3P.113).
  The Journal of Immunology 2015 Matthew Rausch, Todd Metzger, Michael Waterfield, Jessica Cortez, Mark Anderson, Karen Hastings
• COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis.
  Nature genetics 2015 Watkin LB, Jessen B, Wiszniewski W, Vece TJ, Jan M, Sha Y, Thamsen M, Santos-Cortez RL, Lee K, Gambin T, Forbes LR, Law CS, Stray-Pedersen A, Cheng MH, Mace EM, Anderson MS, Liu D, Tang LF, Nicholas …
• Erratum: Corrigendum: The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
  Nature Immunology 2014 Michael Waterfield, Imran S Khan, Jessica T Cortez, Una Fan, Todd Metzger, Alexandra Greer, Kayla Fasano, Marc Martinez-Llordella, Joshua L Pollack, David J Erle, Maureen Su, Mark S Anderson
• The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
  Nature immunology 2014 Waterfield M, Khan IS, Cortez JT, Fan U, Metzger T, Greer A, Fasano K, Martinez-Llordella M, Pollack JL, Erle DJ, Su M, Anderson MS
• Autoimmunity's collateral damage: Immunodeficiency hints at autoreactivity to cytokines.
  Nature medicine 2011 Waterfield M, Anderson MS
• Clues to immune tolerance: the monogenic autoimmune syndromes.
  Annals of the New York Academy of Sciences 2010 Waterfield M, Anderson MS
• NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase.
  Molecular cell 2003 Waterfield MR, Zhang M, Norman LP, Sun SC