Mark Anderson, MD, PhD

Professor of Medicine
Robert B. Friend and Michelle M. Friend Endowed Chair in Diabetes Research
Diabetes Center
+1 415 502-8052

EDUCATION/CLINICAL TRAINING
MD: MD, PhD, University of Chicago, 1994
Residency: University of Minnesota, MD, Internal Medicine, 1994-1997
Chief Resident, University of Minnesota 1997-1998
Fellowship: Massachusetts General Hospital, Adult Endocrinology, 1998-2001
Board Certification: Endocrinology and Metabolism, 2001, Renewed 2012

ACADEMIC INTERESTS
The main research interest of our laboratory group is to examine the genetic control of autoimmune diseases to gain a better understanding of the mechanisms by which immune tolerance is broken. A major focus of our lab group is a human autoimmune syndrome called Autoimmune Polyglandular Syndrome Type 1 (APS1 or APECED), which is classically manifested by an autoimmune attack directed at multiple endocrine organs. This disease is inherited in a monogenic autosomal recessive fashion and the defective gene has been identified and is called Aire (for autoimmune regulator). Aire knockout mice, like their human counterparts, develop an autoimmune disease that is targeted to multiple organs. Through the use of the mouse model we, along with others, have determined that Aire plays an important role in immune tolerance by promoting the expression of many self proteins in specialized antigen presenting cells in the thymus called medullary epithelial cells (mTEC’s).

Recently, we have determined that this process is not only critical in the thymus, but also in peripheral lymphoid organs. Current studies in the lab are directed at further understanding the relative contribution of specialized Aire-expressing cells to immune tolerance in multiple autoimmune disease models. In addition to these ongoing studies, our laboratory is also interested the pathogenesis of autoimmune diabetes and in developing other models of autoimmune disease by using transgenic, knockout, and knock-in approaches.

CLINICAL INTERESTS:
Type 1 diabetes and associated autoimmune disorders

Appointments: 415-353-2350

Publications: 

Thymic tolerance as a key brake on autoimmunity.

Nature immunology

Cheng M, Anderson MS

Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance.

Immunity

Perry JSA, Russler-Germain EV, Zhou YW, Purtha W, Cooper ML, Choi J, Schroeder MA, Salazar V, Egawa T, Lee BC, Abumrad NA, Kim BS, Anderson MS, DiPersio JF, Hsieh CS

Author Correction: Discovery of stimulation-responsive immune enhancers with CRISPR activation.

Nature

Simeonov DR, Gowen BG, Boontanrart M, Roth TL, Gagnon JD, Mumbach MR, Satpathy AT, Lee Y, Bray NL, Chan AY, Lituiev DS, Nguyen ML, Gate RE, Subramaniam M, Li Z, Woo JM, Mitros T, Ray GJ, Curie GL, Naddaf N, Chu JS, Ma H, Boyer E, Van Gool F, Huang H, Liu R, Tobin VR, Schumann K, Daly MJ, Farh KK, Ansel KM, Ye CJ, Greenleaf WJ, Anderson MS, Bluestone JA, Chang HY, Corn JE, Marson A

CD36 Mediates Cell-Surface Antigens to Promote Thymic Development of the Regulatory T Cell Receptor Repertoire and Allo-tolerance.

Immunity

Perry JSA, Russler-Germain EV, Zhou YW, Purtha W, Cooper ML, Choi J, Schroeder MA, Salazar V, Egawa T, Lee BC, Abumrad NA, Kim BS, Anderson MS, DiPersio JF, Hsieh CS

Revealing the specificity of regulatory T cells in murine autoimmune diabetes.

Proceedings of the National Academy of Sciences of the United States of America

Spence A, Purtha W, Tam J, Dong S, Kim Y, Ju CH, Sterling T, Nakayama M, Robinson WH, Bluestone JA, Anderson MS, Tang Q

Autoimmune Polyendocrine Syndromes.

The New England journal of medicine

Husebye ES, Anderson MS, Kämpe O

Insights into immune tolerance from AIRE deficiency.

Current opinion in immunology

Proekt I, Miller CN, Lionakis MS, Anderson MS

Revisiting the Road Map of Medullary Thymic Epithelial Cell Differentiation.

Journal of immunology (Baltimore, Md. : 1950)

Michel C, Miller CN, Küchler R, Brors B, Anderson MS, Kyewski B, Pinto S

Combination central tolerance and peripheral checkpoint blockade unleashes antimelanoma immunity.

JCI insight

Bakhru P, Zhu ML, Wang HH, Hong LK, Khan I, Mouchess M, Gulati AS, Starmer J, Hou Y, Sailer D, Lee S, Zhao F, Kirkwood JM, Moschos S, Fong L, Anderson MS, Su MA

Discovery of stimulation-responsive immune enhancers with CRISPR activation.

Nature

Simeonov DR, Gowen BG, Boontanrart M, Roth TL, Gagnon JD, Mumbach MR, Satpathy AT, Lee Y, Bray NL, Chan AY, Lituiev DS, Nguyen ML, Gate RE, Subramaniam M, Li Z, Woo JM, Mitros T, Ray GJ, Curie GL, Naddaf N, Chu JS, Ma H, Boyer E, Van Gool F, Huang H, Liu R, Tobin VR, Schumann K, Daly MJ, Farh KK, Ansel KM, Ye CJ, Greenleaf WJ, Anderson MS, Bluestone JA, Chang HY, Corn JE, Marson A

Exome Sequencing Reveals Mutations in AIRE as a Cause of Isolated Hypoparathyroidism.

The Journal of clinical endocrinology and metabolism

Li D, Streeten EA, Chan A, Lwin W, Tian L, Pellegrino da Silva R, Kim CE, Anderson MS, Hakonarson H, Levine MA

Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4.

Proceedings of the National Academy of Sciences of the United States of America

Sagan SA, Winger RC, Cruz-Herranz A, Nelson PA, Hagberg S, Miller CN, Spencer CM, Ho PP, Bennett JL, Levy M, Levin MH, Verkman AS, Steinman L, Green AJ, Anderson MS, Sobel RA, Zamvil SS

AIRE expands: new roles in immune tolerance and beyond.

Nature reviews. Immunology

Anderson MS, Su MA

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

Editorial overview: Autoimmunity.

Current opinion in immunology

Anderson MS, Mackay F

Identification of MiR-205 As a MicroRNA That Is Highly Expressed in Medullary Thymic Epithelial Cells.

PloS one

Khan IS, Park CY, Mavropoulos A, Shariat N, Pollack JL, Barczak AJ, Erle DJ, McManus MT, Anderson MS, Jeker LT

Brd4 bridges the transcriptional regulators, Aire and P-TEFb, to promote elongation of peripheral-tissue antigen transcripts in thymic stromal cells.

Proceedings of the National Academy of Sciences of the United States of America

Yoshida H, Bansal K, Schaefer U, Chapman T, Rioja I, Proekt I, Anderson MS, Prinjha RK, Tarakhovsky A, Benoist C, Mathis D

Transglutaminase 4 as a prostate autoantigen in male subfertility.

Science translational medicine

Landegren N, Sharon D, Shum AK, Khan IS, Fasano KJ, Hallgren Å, Kampf C, Freyhult E, Ardesjö-Lundgren B, Alimohammadi M, Rathsman S, Ludvigsson JF, Lundh D, Motrich R, Rivero V, Fong L, Giwercman A, Gustafsson J, Perheentupa J, Husebye ES, Anderson MS, Snyder M, Kämpe O

Too much of a good thing: NLRC4 and autoinflammation.

The Journal of experimental medicine

Anderson MS

Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance.

The Journal of experimental medicine

Khan IS, Mouchess ML, Zhu ML, Conley B, Fasano KJ, Hou Y, Fong L, Su MA, Anderson MS

Spontaneous development of autoimmune uveitis Is CCR2 dependent.

The American journal of pathology

Chen YF, Zhou D, Metzger T, Gallup M, Jeanne M, Gould DB, Anderson MS, McNamara NA

Panostotic expansile bone disease with massive jaw tumor formation and a novel mutation in the signal peptide of RANK.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Schafer AL, Mumm S, El-Sayed I, McAlister WH, Horvai AE, Tom AM, Hsiao EC, Schaefer FV, Collins MT, Anderson MS, Whyte MP, Shoback DM

Canonical microRNAs in thymic epithelial cells promote central tolerance.

European journal of immunology

Khan IS, Taniguchi RT, Fasano KJ, Anderson MS, Jeker LT

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

BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.

Science translational medicine

Shum AK, Alimohammadi M, Tan CL, Cheng MH, Metzger TC, Law CS, Lwin W, Perheentupa J, Bour-Jordan H, Carel JC, Husebye ES, De Luca F, Janson C, Sargur R, Dubois N, Kajosaari M, Wolters PJ, Chapman HA, Kämpe O, Anderson MS

Lineage tracing and cell ablation identify a post-Aire-expressing thymic epithelial cell population.

Cell reports

Metzger TC, Khan IS, Gardner JM, Mouchess ML, Johannes KP, Krawisz AK, Skrzypczynska KM, Anderson MS

Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4? T cells.

Immunity

Gardner JM, Metzger TC, McMahon EJ, Au-Yeung BB, Krawisz AK, Lu W, Price JD, Johannes KP, Satpathy AT, Murphy KM, Tarbell KV, Weiss A, Anderson MS

Insights into type 1 diabetes from the autoimmune polyendocrine syndromes.

Current opinion in endocrinology, diabetes, and obesity

Cheng MH, Anderson MS

Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development.

Cell stem cell

Parent AV, Russ HA, Khan IS, LaFlam TN, Metzger TC, Anderson MS, Hebrok M

Autoimmune retinopathy in a patient with autoimmune polyendocrine syndrome type I.

Ocular immunology and inflammation

Breunig A, Lee MS, Miller BS, Binstadt BA, Anderson MS, Montezuma S

Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection.

Proceedings of the National Academy of Sciences of the United States of America

Taniguchi RT, DeVoss JJ, Moon JJ, Sidney J, Sette A, Jenkins MK, Anderson MS

Monogenic autoimmunity.

Annual review of immunology

Cheng MH, Anderson MS

Control of central and peripheral tolerance by Aire.

Immunological reviews

Metzger TC, Anderson MS

Myocarditis: a defect in central immune tolerance?

The Journal of clinical investigation

Metzger TC, Anderson MS

Aire and T cell development.

Current opinion in immunology

Anderson MS, Su MA

The role of Aire in clonal selection.

Immunology and cell biology

Taniguchi RT, Anderson MS

Clues to immune tolerance: the monogenic autoimmune syndromes.

Annals of the New York Academy of Sciences

Waterfield M, Anderson MS

An autoimmune response to odorant binding protein 1a is associated with dry eye in the Aire-deficient mouse.

Journal of immunology (Baltimore, Md. : 1950)

DeVoss JJ, LeClair NP, Hou Y, Grewal NK, Johannes KP, Lu W, Yang T, Meagher C, Fong L, Strauss EC, Anderson MS

Identification of an autoantigen demonstrates a link between interstitial lung disease and a defect in central tolerance.

Science translational medicine

Shum AK, DeVoss J, Tan CL, Hou Y, Johannes K, O'Gorman CS, Jones KD, Sochett EB, Fong L, Anderson MS

AIRE in the thymus and beyond.

Current opinion in immunology

Gardner JM, Fletcher AL, Anderson MS, Turley SJ

An aberrant prostate antigen-specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans.

The Journal of clinical investigation

Hou Y, DeVoss J, Dao V, Kwek S, Simko JP, McNeel DG, Anderson MS, Fong L

A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy.

The Journal of experimental medicine

Louvet C, Kabre BG, Davini DW, Martinier N, Su MA, DeVoss JJ, Rosenthal WL, Anderson MS, Bour-Jordan H, Bluestone JA

The role of X-linked FOXP3 in the autoimmune susceptibility of Turner Syndrome patients.

Clinical immunology (Orlando, Fla.)

Su MA, Stenerson M, Liu W, Putnam A, Conte F, Bluestone JA, Anderson MS

Update in endocrine autoimmunity.

The Journal of clinical endocrinology and metabolism

Anderson MS

Effector mechanisms of the autoimmune syndrome in the murine model of autoimmune polyglandular syndrome type 1.

Journal of immunology (Baltimore, Md. : 1950)

Devoss JJ, Shum AK, Johannes KP, Lu W, Krawisz AK, Wang P, Yang T, Leclair NP, Austin C, Strauss EC, Anderson MS

Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.

The Journal of experimental medicine

Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, Bluestone JA

Deletional tolerance mediated by extrathymic Aire-expressing cells.

Science (New York, N.Y.)

Gardner JM, Devoss JJ, Friedman RS, Wong DJ, Tan YX, Zhou X, Johannes KP, Su MA, Chang HY, Krummel MF, Anderson MS

Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire.

The Journal of clinical investigation

Su MA, Giang K, Zumer K, Jiang H, Oven I, Rinn JL, Devoss JJ, Johannes KP, Lu W, Gardner J, Chang A, Bubulya P, Chang HY, Peterlin BM, Anderson MS

Expression of Aire and the early wave of apoptosis in spermatogenesis.

Journal of immunology (Baltimore, Md. : 1950)

Schaller CE, Wang CL, Beck-Engeser G, Goss L, Scott HS, Anderson MS, Wabl M

Small proline-rich protein 1B (SPRR1B) is a biomarker for squamous metaplasia in dry eye disease.

Investigative ophthalmology & visual science

Li S, Nikulina K, DeVoss J, Wu AJ, Strauss EC, Anderson MS, McNamara NA

What's new in the Aire?

Trends in immunology

Cheng MH, Shum AK, Anderson MS

Lessons on immune tolerance from the monogenic disease APS1.

Current opinion in genetics & development

DeVoss JJ, Anderson MS

Spontaneous autoimmunity prevented by thymic expression of a single self-antigen.

The Journal of experimental medicine

DeVoss J, Hou Y, Johannes K, Lu W, Liou GI, Rinn J, Chang H, Caspi RR, Caspi R, Fong L, Anderson MS

Modifier loci condition autoimmunity provoked by Aire deficiency.

The Journal of experimental medicine

Jiang W, Anderson MS, Bronson R, Mathis D, Benoist C

The cellular mechanism of Aire control of T cell tolerance.

Immunity

Anderson MS, Venanzi ES, Chen Z, Berzins SP, Benoist C, Mathis D

The NOD mouse: a model of immune dysregulation.

Annual review of immunology

Anderson MS, Bluestone JA

Aire: an update.

Current opinion in immunology

Su MA, Anderson MS

Autoimmune endocrine disease.

Current opinion in immunology

Anderson MS

Projection of an immunological self shadow within the thymus by the aire protein.

Science (New York, N.Y.)

Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D

Enhanced antigen presentation in the absence of the invariant chain endosomal localization signal.

The Journal of experimental medicine

Anderson MS, Swier K, Arneson L, Miller J

Invariant chain can function as a chaperone protein for class II major histocompatibility complex molecules.

Proceedings of the National Academy of Sciences of the United States of America

Anderson MS, Miller J