Dr. Mathis obtained a PhD from the University of Rochester and performed postdoctoral studies at the Laboratoire de Génétique Moléculaire des Eucaryotes in Strasbourg, France and Stanford University Medical Center. She returned to Strasbourg at the end of 1983, establishing a laboratory at the LGME [later the Institut de Genetique et de Biologie Moleculare et Cellulaire (IGBMC)] in conjunction with Dr. Christophe Benoist. The lab moved to the Joslin Diabetes Center in Boston in 1999. Through 2008, Dr. Mathis was a Professor of Medicine at Brigham and Women’s Hospital and Harvard Medical School (HMS), and Associate Research Director and Head of the Section on Immunology and Immunogenetics at Joslin. She held visiting professorships at the Walter and Eliza Hall Institute in Melbourne in 1997/8 and at Tokyo University in 2008. Dr Mathis is currently a Professor in the Department of Immunology at HMS and holder of the Morton Grove-Rasmussen Chair in Immunohematology. She is also a Principal Faculty Member at the Harvard Stem Cell Institute and an Associate Faculty Member of the Broad Institute.

She presently serves on advisory boards of Rockefeller University, the Howard Hughes Medical Institute, Genentech, Pfizer, Amgen, Janssen, Xaira Therapeutics and Goldman Sachs Life Sciences (amongst others), and of several research institutes worldwide. She has co-founded several biotech start-ups: Tempero Therapeutics, Brake Inc., Trex Bio, Abata Therapeutics and Zag Bio. Dr. Mathis was elected to the US National Academy of Sciences in 2003, the German Academy in 2007, and the American Academy of Arts and Sciences in 2012. She received the Excellence in Science Award from the Federation of American Societies in Experimental Biology in 2016, the inaugural Menarini Prize for Outstanding Woman Immunologist from the International Union of Immunological Societies in 2023, and the William B Coley Award for Distinguished Research in Basic Immunology from the Cancer Research Institute in 2024; and was named a Distinguished Fellow of the American Association of Immunologists in 2025. Her lab works in the fields of T cell differentiation, immunological tolerance, autoimmunity and inflammation. She has trained over 180 students and postdoctoral fellows from all over the world.