Mark Anderson, MD, PhD

Director, Medical Scientist Training Program
Co-Chair, UCSF Immunology Program Steering Committee
Professor
Diabetes Center
Research Overview: 

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).

APS1 patients also harbor a rich assortment of different autoimmune diseases and autoantibodies that indicate the specificity of the autoimmune response. Recently, we have established collaborations characterizing these autoantibodies with the DeRisi lab at UCSF using a proteome wide approach. This has revealed some unexpected phenotypes that have helped open new areas to investigate. In addition, APS1 patients show severe susceptibility to COVID-19 due to a paradoxical autoimmune response against type 1 interferons. In a collaborative effort with the DeRisi and Casanova lab at the Rockefeller, we have come to determine that type 1 interferon autoantibodies underlie a significant portion of severe COVID-19 cases, even in vaccinated patients. We are now exploring how these type 1 interferon autoantibodies are more broadly triggered.

Beyond APS1, we are also exploring other single gene defects that are associated with autoimmune diseases like type 1 diabetes. Our approach has been to study both rare human families with strong inheritance of type 1 diabetes and also to model this in mouse. For example, we recently identified that STAT3 gain of function mutations help trigger type 1 diabetes through an exuberant CD8 T cell response in the pancreatic islets.

Taken together, our general approach to unlocking the complexity of autoimmunity has been to utilize outliers as a window into this fascinating clinical problem.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Human Genetics
Research Summary: 
The Genetic Control of Autoimmune Disease
Mentorship Development: 

11/23/20    Building Community in the UCSF MSTP 
2/18/21    Three Truths and Three Tries: Facing and Overcoming Critical Social Justice Challenges at the Micro, Mezzo, and Macro Levels    

Websites

Publications: 

A ROR?t+ cell instructs gut microbiota-specific Treg cell differentiation.

Nature

Kedmi R, Najar TA, Mesa KR, Grayson A, Kroehling L, Hao Y, Hao S, Pokrovskii M, Xu M, Talbot J, Wang J, Germino J, Lareau CA, Satpathy AT, Anderson MS, Laufer TM, Aifantis I, Bartleson JM, Allen PM, Paidassi H, Gardner JM, Stoeckius M, Littman DR

Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes.

JCI insight

Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC

Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized Lipodystrophy.

Diabetes

Mandel-Brehm C, Vazquez SE, Liverman C, Cheng M, Quandt Z, Kung AF, Parent A, Miao B, Disse E, Cugnet-Anceau C, Dalle S, Orlova E, Frolova E, Alba D, Michels A, Oftedal BE, Lionakis MS, Husebye ES, Agarwal AK, Li X, Zhu C, Li Q, Oral E, Brown R, Anderson MS, Garg A, DeRisi JL

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs.

Science immunology

Bastard P, Vazquez S, Liu J, Laurie MT, Wang CY, Gervais A, Le Voyer T, Bizien L, Zamecnik C, Philippot Q, Rosain J, Catherinot E, Willmore A, Mitchell AM, Bair R, Garçon P, Kenney H, Fekkar A, Salagianni M, Poulakou G, Siouti E, Sahanic S, Tancevski I, Weiss G, Nagl L, Manry J, Duvlis S, Arroyo-Sánchez D, Paz Artal E, Rubio L, Perani C, Bezzi M, Sottini A, Quaresima V, Roussel L, Vinh DC, Reyes LF, Garzaro M, Hatipoglu N, Boutboul D, Tandjaoui-Lambiotte Y, Borghesi A, Aliberti A, Cassaniti I, Venet F, Monneret G, Halwani R, Sharif-Askari NS, Danielson J, Burrel S, Morbieu C, Stepanovskyy Y, Bondarenko A, Volokha A, Boyarchuk O, Gagro A, Neuville M, Neven B, Keles S, Hernu R, Bal A, Novelli A, Novelli G, Saker K, Ailioaie O, Antolí A, Jeziorski E, Rocamora-Blanch G, Teixeira C, Delaunay C, Lhuillier M, Le Turnier P, Zhang Y, Mahevas M, Pan-Hammarström Q, Abolhassani H, Bompoil T, Dorgham K, COVID HGE consortium † , French COVID study group † , COMET consortium † , Gorochov G, Laouenan C, Rodríguez-Gallego C, Ng LFP, Renia L, Pujol A, Belot A, Raffi F, Allende LM, Martinez-Picado J, Ozcelik T, Keles S, Imberti L, Notarangelo LD, Troya J, Solanich X, Zhang SY, Puel A, Wilson MR, Trouillet-Assant S, Abel L, Jouanguy E, Ye CJ, Cobat A, Thompson LM, Andreakos E, Zhang Q, Anderson MS, Casanova JL, DeRisi JL

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

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

Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Michailidis E, Hoffmann HH, Eto S, Garcia-Prat M, Bizien L, Parra-Martínez A, Yang R, Haljasmägi L, Migaud M, Särekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garçon P, Rivière JG, Lagier JC, Gentile S, Rosen LB, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Mégarbane B, Triantafyllia V, Fekkar A, Heath JR, Franco JL, Anaya JM, Solé-Violán J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte OM, Zhang Y, Snow AL, Holland SM, Biggs CM, Moncada-Vélez M, Arias AA, Lorenzo L, Boucherit S, Anglicheau D, Planas AM, Haerynck F, Duvlis S, Ozcelik T, Keles S, Bousfiha AA, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarström Q, Hammarström L, Dupont A, Kurolap A, Metz CN, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros LA, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye SG, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann NY, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes LF, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig MC, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer AH, Kennelly SP, Bourke NM, Halwani R, Sharif-Askari FS, Dorgham K, Sallette J, Sedkaoui SM, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh DC, Erikstrup C, Condino-Neto A, Prando C, Bondarenko A, Spaan AN, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton RP, Mane S, HGID Lab, COVID Clinicians, COVID-STORM Clinicians, NIAID Immune Response to COVID Group, NH-COVAIR Study Group, Danish CHGE, Danish Blood Donor Study, St. James's Hospital, SARS CoV2 Interest Group, French COVID Cohort Study Group, Imagine COVID-Group, Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank Investigators, COVID Human Genetic Effort, CP-COVID-19 Group, CONSTANCES cohort, 3C-Dijon Study, Cerba Health-Care, Etablissement Français du Sang Study group, Anderson MS, Boisson B, Béziat V, Zhang SY, Andreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, de Lamballerie X, Burdet C, Bouadma L, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen PK, Piemonti L, Rodríguez-Gallego C, Notarangelo LD, Su HC, Kisand K, Okada S, Puel A, Jouanguy E, Rice CM, Tiberghien P, Zhang Q, Casanova JL, Abel L, Cobat A