Michael Waterfield, MD, PhD

Asst Professor In Residence
Pediatrics
+1 415 353-7337

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.

Publications: 

Aire in Autoimmunity.

Annual review of immunology

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

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)

Sin JH, Kashyap S, Acenas D, Cortez JT, Lee J, Marson A, Matloubian M, Waterfield MR

The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.

The Journal of experimental medicine

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

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

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

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

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

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 SK, Nahmod K, Makedonas G, Canter DL, Kwok PY, Hicks J, Jones KD, Penney S, Jhangiani SN, Rosenblum MD, Dell SD, Waterfield MR, Papa FR, Muzny DM, Zaitlen N, Leal SM, Gonzaga-Jauregui C, Boerwinkle E, Eissa NT, Gibbs RA, Lupski JR, Orange JS, Shum AK

Erratum: Corrigendum: The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.

Nature immunology

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

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

Clues to immune tolerance: the monogenic autoimmune syndromes.

Annals of the New York Academy of Sciences

Waterfield M, Anderson MS