Dr. Fox received his undergraduate degree from the Massachusetts Institute of Technology (1970-1974), and his M.D. degree from Harvard Medical School (1974-1978). Following training in Internal Medicine and Rheumatology at the Brigham and Women's Hospital (1978-1982), he pursued a Research Fellowship with Drs. Stuart Schlossman and Ellis Reinherz at the Dana-Farber Cancer Center (1982-l985) in the area of human T cell activation. He was appointed Assistant Professor in the Division of Rheumatology at the University of Michigan in 1985 and was promoted to Associate Professor and Division Chief in 1990 and Professor in 1995. In 2018 he stepped down from the Division Chief position after 28 years in that role. He also served from 1987-2023 as Director of the Hybridoma Core facility for the University of Michigan Medical School and as Director of the University of Michigan Clinical Autoimmunity Center of Excellence, funded by the NIH from 2014-2024. He also directed several other Centers and Programs at the University of Michigan, including the Multipurpose Arthritis and Musculoskeletal Diseases Center, the Rheumatic Disease Core Center and the T32 rheumatology Training Grant. Dr. Fox holds the Frederick Huetwell and William D Robinson endowed Professorship in Rheumatology. He is currently a Deputy Director of the NIH-funded Immune Tolerance Network and cochairs the Inflammation and Immunity Steering Committee of the Biomarkers Consortium in the Foundation for the NIH.
Dr. Fox is a member of the American Society for Clinical Investigation and the Association of American Physicians. He is a Master of the American College of Rheumatology (ACR), and served in numerous volunteer roles in the ACR,
In 2007-2008, Dr. Fox served as the seventy-first President of the American College of Rheumatology and the sixth ACR President from the University of Michigan.

Dr. Fox's research focuses on defining and characterizing pathways of human T cell activation, determining the role of these pathways in the pathogenesis of autoimmune disease, investigating T cell interactions with synovial fibroblasts, understanding pathways of inflammation in arthritic joints, and understanding the role of interleukin-17 in arthritis. He is also studying the pathogenesis and treatment of scleroderma. He is the author of more than 270 scientific papers and book chapters and has served on the Editorial Board of Arthritis & Rheumatism and as an Associate Editor of the Journal of Immunology, the Journal of Clinical Investigation and JCI Insight.

Research in Dr. Fox's laboratory is directed at defining and characterizing pathways of human T cell activation, and the role of these pathways in the pathogenesis of autoimmune diseases, especially rheumatoid arthritis. In organ-targeted immune-mediated diseases such as rheumatoid arthritis, the interactions between lymphocytes and cells characteristic of the targeted tissue are of special interest. This laboratory has focused extensively on understanding how T cells and synovial fibroblasts interact and has shown that each cell type activates the other. Synovial fibroblasts can present both superantigens and peptide antigens to T cells, including autoantigens that may be important in the development of arthritis. Conversely, T cells can activate synovial fibroblasts, even in the absence of antigen recognition. The response of fibroblasts to T cells is enhanced by interleukin-17, a cytokine now known to be characteristic of a distinctive effector T cell subset.
Studies in vivo in mice with collagen-induced arthritis, a model system for rheumatoid arthritis, also have shed light on the importance of interleukin-17-producing T cells in joint inflammation. Dr. Fox's laboratory developed a strategy to control collagen arthritis by injection of myeloid dendritic cells transfected with a gene construct that leads to the expression of interleukin-4. These genetically modified dendritic cells are potent regulators of the IL-17 response, although TH-17 cells can ultimately become resistant to the effects of IL-4. Other experiments focus on the molecular characterization of TH-17 cells that are either sensitive or resistant to immunoregulation. Resistant TH-17 cells might be of special importance in the pathogenesis of chronic immune-mediated diseases in humans.

In recent years Dr. Fox's laboratory has focused on two new areas of investigation. One of these is the discovery that the CD13 molecule, known as a myeloid cell surface N-aminopeptidase is expressed, and shed by synovial fibroblasts and other cell types that participate in organ-targeted autoimmunity. This sCD13 is a powerful inflammatory mediator, with chemotactic, angiogenic, arthritogenic and immunothrombotic properties, through binding to its receptors, which we have identified as the B1R and PAR4 molecules.

The other new area of research concerns the lymphocyte surface molecule CD6 and its ligands. Working closely with the collaborating laboratory of Dr. Feng Lin at the Cleveland Clinic, an important role for CD6 has been identified in multiple autoimmune diseases and in their animal models. An anti-CD6 monoclonal antibody (mAb) that was generated in Dr. Fox's laboratory, is highly effective in the treatment of autoimmune diseases in CD6-humanized mice. Drs. Fox and Lin have also defined 2 new ligands of CD6, that are important in both autoimmunity and cancer. Furthermore, Dr. Fox's group has shown that his anti-CD6 mAb stimulates lymphocytes to kill cancer cells, with a generally more potent effect than checkpoint inhibitors currently used as cancer immunotherapies, despite their propensity to induce autoimmunity.. These discoveries pinpoint CD6 as a compelling new target for many cancers and autoimmune diseases. In 2023 Drs. Fox and Lin, together with the Cleveland Clinic and the University of Michigan, formed a new company, Abcon Therapeutics, to develop and test novel biologic therapeutics directed at CD6 and its ligands.