Stanford School of Medicine
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Key Documents

PDFNIH Biosketch available Online PDFCurriculum Vitae available Online

C. Garrison Fathman

Contact Information

  • Clinical Offices
    Immunology & Rheumatology Clinic 300 Pasteur Dr A175 MC 5309 Stanford, CA 94305
    Telephone Work (650) 723-6961 Fax (650) 725-8418
  • Academic Offices
    Personal Information
    Email cfathman@stanford.edu Tel (650) 723-7887, (650) 725-6319
    Administrative Contact
    Carol Figueroa Administrator/Assistant to Dr. C. Garrison Fathman Tel Work 650-725-6319
    Not for medical emergencies or patient use

Clinical Focus

  • Immunology
  • Immunology and Rheumatology

Administrative Appointments

  • Associate Director, ITI Institute Stanford , (2008– present )
  • President, Federation of Clinical Immunology Societies (FOCIS) , (2000– 2005 )
  • Division Chief, Division of Immunology and Rheumatology, Stanford University Medical Center , (1997– present )
  • Director, Center for Clinical Immunology at Stanford (CCIS) , (1993– present )

Professional Education

  • National Institute of Health (1975) MD
  • SUMC - Graduate Medical Education (1973) CA
  • Mary Hitchcock Mem Hosp (1971) NH
  • Mary Hitchcock Mem Hosp (1971) NH
  • Mary Hitchcock Mem Hosp (1970) NH
  • Washington University School Of Medicine (1969) MO
  • B.A., Univ. Kentucky, Lexington Pre-Med (1964)
  • M.D., Washington Univ., St. Louis Medicine (1969)

Graduate & Fellowship Program Affiliations

Industry Relationships

Stanford is committed to ethical and transparent interactions with our industry partners. It is our policy to disclose payments of $5,000 or more, equity valued at $5,000 or more in a publicly traded company, or any equity in a privately held company, to physicians and scientists employed by Stanford University from companies or other commercial entities with which they interact as part of their professional activities. 

  • Consulting: Bayhill, Nodality, lumen
  • Equity: Bayhill, Nodality, lumen

Research Interests

My laboratory of molecular and cellular immunology is interested in mechanisms of T cell anergy and the pathophysiology and immunotherapy of preclinical animal models of autoimmune disease.
I. T Cell Anergy: We have identified a ubiquitin E3 ligase (GRAIL) that seems to be central to the control of T cell anergy. We developed a novel prokaryotic system to screen for E3 ligase substrates and identified RhoGDI as an E3 substrate of GRAIL. Expression of GRAIL in Jurkat T cells resulted in inhibition of Rho activity. Dominant active Rho overcame the GRAIL phenotype and dominant negative Rho blocked IL-2 transcription. Using two-hybrid technology to identify proteins that bound the lumenal or extracellular domain of GRAIL identified CD151, a member of the tetraspanin family of membrane proteins. GRAIL over-expression promoted polyubiquitination of all tested tetraspanins. GRAIL mediated ubiquitination of tetraspanins resulted in proteasomal degradation and loss of cell surface expression. These findings identify for the first time an E3 ligase with a substrate-binding domain spatially restricted by a membrane from its ubiquitination machinery and an E3 ligase for the tetraspanin family.
II. Gene Therapy: Human rheumatoid arthritis is a “disease” that has many phenotypes, ranging from slowly to rapidly progressive arthritis, from joint disease predominant to dominant extra-articular manifestations. Current murine models of RA include several that relate to one or more of these phenotypes. We hypothesize that the local delivery of anti-inflammatory proteins via adoptive cellular gene therapy using syngeneic dendritic cells (DCs) transduced to express immunoregulatory proteins, in three murine models of RA, will provide therapeutic effect both in the prevention of disease onset and in therapy of established disease, and by studying all three models, we may identify different mechanisms of effect, or discover that different therapeutic agents are required for one versus the other model. Furthermore, using cDNA analysis of various should allow identification of gene expression patterns in inflamed versus normal tissues from mice successfully treated by gene therapy. These data may identify the mechanism(s) of therapeutic intervention.
III. Regulatory T cells: In an attempt to study the potential therapeutic uses of Tregs, we settled on a murine model of graft versus host disease (GVHD). We initially demonstrated that donor-derived Tregs inhibited lethal GVHD after allogeneic bone marrow transplantation. More recently we demonstrated in host mice with leukemia and lymphoma, that Tregs suppressed the early expansion of alloreactive donor T cells and their capacity to induce GVHD without abrogating their GVT effector function, mediated primarily by the perforin lysis pathway.
We also examined the differential effect of CD62L+ and CD62L- subsets of Tregs on T1D transfer and on GVHD-related mortality. We demonstrated that CD4+CD25+ splenocytes inhibited diabetes in co-transfer with islet-infiltrating cells. Furthermore, CD62L expression was necessary for this disease delaying effect of Tregs in vivo, but not for their suppressor function in vitro. These data demonstrated that CD62L+Tregs but not CD62L-Tregs delayed diabetes transfer, and that Tregs are comprised of at least two sub-populations that behave differently in co-transfer in despite demonstrating equivalent suppressor functions in vitro. Similarly, in the GVHD mouse model, although both L selectin positive and L selectin negative subpopulations showed the characteristic features of Tregs in vitro, in co-transfer with donor CD4 + CD25- T cells, only the CD62L+ subset of Tregs prevented severe tissue damage to the colon, and protected recipients from lethal aGVHD. These findings, obtained in collaboration with Dr. Negrin, suggest that the ability of Tregs to efficiently enter secondary lymphoid organs is a prerequisite for their protective function in aGVHD.

Publications