C. Garrison Fathman


Bio:   Dr. Fathman is an example of a clinician scientist who has developed a clear vision for implementation of translational research. He has over 300 publications, many of them in the top peer-reviewed journals including Science, Nature, Cell, Journal of Experimental Medicine, JCI, Immunity, Nature Medicine and Nature Immunology. Among Dr. Fathman’s seminal contributions to his field, is the initial cloning of CD4 T lymphocytes while he was a member of the Basel Institute for Immunology. There he met and collaborated with Hans Hengartner who had studied with Rolf Zinkernagle. The use of soft agar seeding of activated cells by Rolf had allowed the cloning of what are now called hybridomas and drove the field monoclonal antibody production. Using this same technology, Dr. Fathman was able to clone allo-reactive T lymphocytes. Dr. Fathman left Basel and became an Associate Professor of Immunology at Mayo Medical School in 1977. There, along with one of his postdoctoral fellows, Masao Kimoto, he adapted the soft agar cloning technology to clone antigen specific CD4 T cells for the first time. The ability to study single T cell specificities allowed rapid advancement in understanding the components of the ternary complex for T cell activation and led Dr. Fathman to identify trans-complementing MHC Class 2 products used in antigen presentation before the biochemical two chain nature of MHC Class 2 products was described. Shortly thereafter, he was the first to identify “idiotypic structures“ on cloned CD4 T cells predating the identification of the T cell receptor for antigen by molecular biological techniques. Dr. Fathman moved from Mayo to Stanford in 1981 and continued his studies on T cell clones, initially identifying the “shared epitope” on HLA Class 2 molecules in RA patients. As a new faculty member at Stanford, he expanded his studies to examine animal models of autoimmunity. The initial observation that led to his studies on the use of monoclonal antibodies to treat animal models of autoimmunity came from the observation that immune unresponsiveness could be induced in mice by the use of anti-CD4 antibodies at the time of antigen immunization. Subsequently he was the first to use anti-CD4 antibodies to block allograft transplant rejection and was the first to use peptides of an autoantigen (myelin basic peptide), to induce a state of “anergy” in mice to ameliorate disease. Initially, anti-CD4 antibody was used to block progression to diabetes in NOD mice. Many subsequent publications were linked to this NOD colony including several seminal observations on pathophysiology, immunotherapy, and gene expression. One major finding was the identification of a non- thymic mechanism for inducing or maintaining peripheral tolerance in NOD that was similar in human T1D. This observation was made possible by comparing gene expression profiles of NOD to a congenic mouse that is isogenic with NOD except for a non-disease permissive MHC, the NOD.B10 mouse. Using microarrays, his lab was able to identify genes whose expression profile was different between the NOD vs NOD.B10 but controlled in a tissue–specific and age-dependent manner. these data were used to identify a gene, DEAF1, that had at least two isoforms, one full-length isoform whose function and protein sequence homology was similar to that of AIRE in the thymus, and a truncated dominant negative isoform, Deaf1-Var1, that lost its transcriptional function but was expressed in the pancreatic lymph nodes of NOD mice and human T1D patients. His studies demonstrated that the canonical isoform was instrumental in controlling the ectopic expression of “self antigens” in the pancreatic lymph nodes (PLN) of NOD.B10 mice and normal non-diabetic individuals, but the non-canonical dominant negative isoform was expressed in the PLN of NOD mice and in human T1D suggesting there was a similar loss of peripheral tolerance in both NOD mice and T1D.

Professional Education

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

Honors & Awards

  • Naomi M. Kanof Award for Distinguished Achievement in Clinical Investigation, Society for Investigative Dermatology (1997)
  • Alumni Achievement Award, Washington University Medical School (1999)
  • President's Award, Clinical Immunology Society (2006)
  • Master, American College of Rheumatology (2007)
  • Founder's Award, Federation of Clinical immunology Societies (2010)
  • Division Teaching Award, Stanford University School of Medicine, Department of Medicine (2011)
  • Mayo Clinic Distinguished Alumnus, Mayo Clinic (2015)

Administrative Appointments

  • President, Federation of Clinical Immunology Societies (FOCIS) (2002 - 2005)
  • Associate Director, ITI Institute Stanford (2008 - Present)
  • President, Clinical Immunology Society (2000 - 2001)
  • Director, Center for Clinical Immunology at Stanford (CCIS) (1993 - Present)
  • Division Chief, Division of Immunology and Rheumatology (1997 - 2014)
  • Associate Editor, Annual Review of Immunology (1981 - 2005)
  • Council, American Society for Clinical Investigation (1984 - 1987)
  • Council, Midwinter Conference of Immunologists (1981 - 1986)