Fathman Lab In the Division of Immunology & Rheumatology

C. Garrison Fathman Laboratory of Cellular and Molecular Immunology

C. Garrison Fathman, M.D.

C. Garrison Fathman, M.D.
Academic Profile

Dr. C. Garrison Fathman, Professor of Medicine and Chief of the Division of Immunology and Rheumatology at Stanford University School of Medicine, also serves as Past Chairman of the Federation of Clinical Immunology Societies (FOCIS) and Director of the Center for Clinical Immunology at Stanford (CCIS).

Dr. Fathman’s contributions in translational medicine in the areas of cellular and molecular immunology, as well as adoptive cellular gene therapy, have brought him international recognition. In particular, he is acclaimed for his establishment and exploitation of the technologies of antigen-specific T-cell cloning and adoptive cellular gene therapy, accomplishments that have facilitated a remarkable series of subsequent advances in understanding conventional immune response and treating autoimmune diseases.

As Founder and Past Chairman of FOCIS, Dr. Fathman led an extremely successful international effort to acknowledge and develop the field of clinical immunology. As Director of the CCIS, the Stanford-based FOCIS Center of Excellence, Dr. Fathman has initiated multi-disciplinary studies to generate novel approaches for the treatment of autoimmune diseases, including insulin-dependent diabetes mellitus, rheumatoid arthritis, and multiple sclerosis. He has also developed state-of-the-art technologies of genomics, proteomics, and metabolomics to integrate approaches to diagnosis, prognosis, and therapy of these diseases.

After receiving his undergraduate degree from the University of Kentucky and his M.D. from Washington University in St. Louis, Dr. Fathman did his residency training at Dartmouth Affiliated Hospitals and completed a fellowship in Immunology and Rheumatology at Stanford University. He then spent four years doing research, first as a Clinical Associate at the Immunology Branch of the National Cancer Institute of the National Institutes of Health and subsequently as a member of the Basel Institute of Immunology in Switzerland. He returned to the United States to join the faculty as Associate Professor of Immunology at the Mayo Clinic in 1977 and was recruited to Stanford University School of Medicine in 1981.

Dr. Fathman is a member of many professional organizations, including the Association of American Physicians, American Society of Clinical Investigation (past Council member) and the American Association of Immunologists, and is the Past-President of the Clinical Immunology Society. He was associate editor of the prestigious Annual Review of Immunology for 25 years and serves on the editorial boards of numerous scientific journals. In addition, he has chaired a variety of national and international professional meetings and has written more than 250 articles on his research. Dr. Fathman also serves on the governing council of TrialNet (a group of studies looking at the prevention and early treatment of type 1 diabetes) and as past-Chairman of the autoimmune disease section of the Immune Tolerance Network.

Dr. Fathman has been and continues to be the recipient of numerous grants from both the National Institutes of Health (NIH) and various Foundations including Juvenile Diabetes Research Foundation (JDRF), American Diabetes Association (ADA), American College of Rheumatology (ACR) and the National Multiple Sclerosis (NMS) Society.

Current Program Project Grants from the NIH include:

He has been the Chairman of a JDRF Center:

He is the Principal Investigator of a Training Grant in Rheumatology:

His current investigator-initiated grants include:

Lastly, Dr. Fathman has been awarded a Mentor-Based Post-doctoral Fellowship from the ADA.

Address: CCSR 2225, Phone 723-7887; Email:

His lab has three main areas of interest:

I. Regulatory T cells and anergy

Two sets of identical T cell clones, one activated and one rendered anergic, have been compared by analyzing message as cDNA utilizing the technique of differential display. This allowed the identification and characterization of a novel gene expressed in the state of anergy; GRAIL, the gene related to anergy in lymphocytes. Transduction of T cell hybridomas with the “anergy specific” gene, GRAIL, a novel E3 ligase, inhibited the expression of IL-2, a cytokine required for T cell growth and differentiation and, expressed in T cells in vivo, rendered the CD4+ T cells anergic to challenge with antigen. We are currently characterizing targets and functions of this ubiquitin E3 ligase. Additionally, CD25+CD4+T regulator cells express GRAIL in vitro and in vivo. The identification and functional characterization of GRAIL will continue during the next several years, and should provide an interesting model of cell signaling and cell biology for gene knock-out studies, gene transfer studies, and transgenic mice. We are using cDNA microarray to look at gene expression patterns in Tregs and the suppressed cells in the CD25+ Treg model and using GVHD as a model of analysis in vivo.

II. Gene Therapy

The lab has extensive experience in the area of retroviral and lentiviral gene transduction of murine T cells and autologous dendritic cells leading to adoptive cell mediated “gene therapy” in murine models of autoimmune disease. This includes, but is not limited to, the delivery of regulatory cytokines, and inhibitors of cytokines including IL-4, IL-10, IL-12p40, and anti-TNF. The models we study include the non-obese diabetic (NOD) mouse model of insulin-dependent diabetes mellitus (IDDM), the collagen-induced arthritis (CIA) and SKG models of human rheumatoid arthritis, and experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. Using bioluminescence and biodistribution studies of luciferase expression, we can follow cell traffic in these models in vivo in real time. Mechanisms of effect are being studied with microarray and qPCR techniques to look at gene expression correlates with phenotype. Transduced MHC negative DCs are not effective in therapy suggesting a T cell interaction.

III. Pathogenesis and response to therapy of autoimmune diseases

The lab studies the NOD animal model of human IDDM, the collagen-induced and the SKG “spontaneous model” of human rheumatoid arthritis in mice, and EAE as a model of multiple sclerosis. Techniques of Microarray, laser-capture microscopy and proteomics are being used to study disease phenotype/gene expression correlates and compare patterns following successful therapy to identify “biomarkers” of success and/or mechanism of action. Interesting patterns of gene expression in pancreatic lymph nodes suggest the possibility of “immunoregulatory” events occurring extrathymically.


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