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: 

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

Single-Dose and Multiple-Dose Pharmacokinetics of Vaniprevir in Healthy Men.

Clinical and translational science

Caro L, de Hoon J, Depré M, Cilissen C, Miller J, Gao W, Panebianco D, Guo Z, Troemel SL, Anderson MS, Uemura N, Butterton J, Wagner J, Wright DH

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

LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity.

The Journal of clinical investigation

Proekt I, Miller CN, Jeanne M, Fasano KJ, Moon JJ, Lowell CA, Gould DB, Anderson MS, DeFranco AL

Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis.

Journal of the American Society of Nephrology : JASN

Landegren N, Pourmousa Lindberg M, Skov J, Hallgren Å, Eriksson D, Lisberg Toft-Bertelsen T, MacAulay N, Hagforsen E, Räisänen-Sokolowski A, Saha H, Nilsson T, Nordmark G, Ohlsson S, Gustafsson J, Husebye ES, Larsson E, Anderson MS, Perheentupa J, Rorsman F, Fenton RA, Kämpe O

AIRE expands: new roles in immune tolerance and beyond.

Nature reviews. Immunology

Anderson MS, Su MA

Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1.

Scientific reports

Landegren N, Sharon D, Freyhult E, Hallgren Å, Eriksson D, Edqvist PH, Bensing S, Wahlberg J, Nelson LM, Gustafsson J, Husebye ES, Anderson MS, Snyder M, Kämpe O

Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns.

Nature immunology

Malhotra D, Linehan JL, Dileepan T, Lee YJ, Purtha WE, Lu JV, Nelson RW, Fife BT, Orr HT, Anderson MS, Hogquist KA, Jenkins MK

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

Central tolerance to self revealed by the autoimmune regulator.

Annals of the New York Academy of Sciences

Chan AY, 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

Autoimmune hepatitis in a murine autoimmune polyendocrine syndrome type 1 model is directed against multiple autoantigens.

Hepatology (Baltimore, Md.)

Hardtke-Wolenski M, Taubert R, Noyan F, Sievers M, Dywicki J, Schlue J, Falk CS, Ardesjö Lundgren B, Scott HS, Pich A, Anderson MS, Manns MP, Jaeckel E

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

Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus.

The Journal of clinical investigation

Price JV, Haddon DJ, Kemmer D, Delepine G, Mandelbaum G, Jarrell JA, Gupta R, Balboni I, Chakravarty EF, Sokolove J, Shum AK, Anderson MS, Cheng MH, Robinson WH, Browne SK, Holland SM, Baechler EC, Utz PJ

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

Efficacy of facemask ventilation techniques in novice providers.

Journal of clinical anesthesia

Gerstein NS, Carey MC, Braude DA, Tawil I, Petersen TR, Deriy L, Anderson MS

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

Defective autoimmune regulator-dependent central tolerance to myelin protein zero is linked to autoimmune peripheral neuropathy.

Journal of immunology (Baltimore, Md. : 1950)

Su MA, Davini D, Cheng P, Giang K, Fan U, DeVoss JJ, Johannes KP, Taylor L, Shum AK, Valenzise M, Meloni A, Bour-Jordan H, 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

Acquired autoimmune polyglandular syndrome, thymoma, and an AIRE defect.

The New England journal of medicine

Cheng MH, Fan U, Grewal N, Barnes M, Mehta A, Taylor S, Husebye ES, Murphy EJ, 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

The sickness unto Deaf.

Nature immunology

Gardner JM, Anderson MS

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

A robust immunoassay for anti-interferon autoantibodies that is highly specific for patients with autoimmune polyglandular syndrome type 1.

Clinical immunology (Orlando, Fla.)

Zhang L, Barker JM, Babu S, Su M, Stenerson M, Cheng M, Shum A, Zamir E, Badolato R, Law A, Eisenbarth GS, Anderson MS

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

T cell activation by processed antigen is equally blocked by I-E and I-A-restricted immunodominant peptides.

European journal of immunology

Lakey EK, Casten LA, Anderson MS, Smolenski LA, Smith JA, Margoliash E, Pierce SK