C. Garrison Fathman

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

Postdoctoral Advisees

Johannes Grisar, Jack Lin, Claudia Sandoval Montes, Laura Su, Xiaobin Tang, Linda Yip

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Immunology
• Medicine

Web Site Links

• My lab site

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. View Full Information

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...

Publications

• Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes. Yip L, Su L, Sheng D, Chang P, Atkinson M, Czesak M, Albert PR, Collier AR, Turley SJ, Fathman CG, Creusot RJ. Nat Immunol. 2009; 10 (9): 1026-33
• Lymphoid-tissue-specific homing of bone-marrow-derived dendritic cells. Creusot RJ, Yaghoubi SS, Chang P, Chia J, Contag CH, Gambhir SS, Fathman CG. Blood. 2009; 113 (26): 6638-47
• Naive CD4 t cell proliferation is controlled by mammalian target of rapamycin regulation of GRAIL expression. Lin JT, Lineberry NB, Kattah MG, Su LL, Utz PJ, Fathman CG, Wu L. J Immunol. 2009; 182 (10): 5919-28
• The transmembrane E3 ligase GRAIL ubiquitinates and degrades CD83 on CD4 T cells. Su LL, Iwai H, Lin JT, Fathman CG. J Immunol. 2009; 183 (1): 438-44
• The single subunit transmembrane E3 ligase gene related to anergy in lymphocytes (GRAIL) captures and then ubiquitinates transmembrane proteins across the cell membrane. Lineberry N, Su L, Soares L, Fathman CG. J Biol Chem. 2008; 283 (42): 28497-505