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: 

Case report: Discovery of a de novo FAM111B pathogenic variant in a patient with an APECED-like clinical phenotype.

Frontiers in immunology

Ferr? EMN, Yu Y, Oikonomou V, Hilfanova A, Lee CR, Rosen LB, Burbelo PD, Vazquez SE, Anderson MS, Barocha A, Heller T, Soldatos A, Holland SM, Walkiewicz MA, Lionakis MS

Autoantigen profiling reveals a shared post-COVID signature in fully recovered and Long COVID patients.

medRxiv : the preprint server for health sciences

Bodansky A, Wang CY, Saxena A, Mitchell A, Takahashi S, Anglin K, Huang B, Hoh R, Lu S, Goldberg SA, Romero J, Tran B, Kirtikar R, Grebe H, So M, Greenhouse B, Durstenfeld MS, Hsue PY, Hellmuth J, Kelly JD, Martin JN, Anderson MS, Deeks SG, Henrich TJ, DeRisi JL, Peluso MJ

Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs.

The Journal of clinical investigation

Casanova JL, Anderson MS

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

Prevalence of type-1 interferon autoantibodies in adults with non-COVID-19 acute respiratory failure.

Respiratory research

Ghale R, Spottiswoode N, Anderson MS, Mitchell A, Wang G, Calfee CS, DeRisi JL, Langelier CR