Professor of Pediatrics
Associate Program Director for Pediatrics, CTSI Clinical Research Center
Phone: (415) 476-3181
Fax: (415) 502-5127
- Harvard University, Cambridge, MA, BA, cum laude, biochemistry, 1967-71
- Harvard Medical School, Harvard MIT Program in Health Sciences & Technology, Boston, MA , MD, 1971-75
- St. Louis Children's Hospital, Washington University, St. Louis, MO, residency, pediatrics, 1975-77
- Washington University, St. Louis, MO, fellowship, infectious disease, 1977-78
- Baylor College of Medicine, Houston, TX, Influenza Research Center and Dept. of Pediatrics, fellowship, pediatric infectious disease and immunology, 1978-79
- Baylor College of Medicine, Houston, TX, Howard Hughes Medical Institute, reseach associate, pediatric infectious diseases, immunology, genetics, 1979-84
- American Board of Pediatrics
- Fellow, American Academy of Pediatrics
- Practitioner of Pediatric Infectious Diseases, Pediatric Infectious Diseases Society
- Inherited disorders of lymphocyte development
- Primary immune disorders
UCSF Program Affiliations
- Member, UCSF Biomedical Sciences Graduate Program (BMS)
- Member, UCSF Immunology Graduate Program
- UCSF Institute for Human Genetics
- UCSF Clinical and Translational Science Institute (CTSI)
- Member, UCSF Pharmaceutical Sciences and Pharmacogenomics Graduate Program
Jennifer Puck, MD, came to UCSF in 2006 as a professor of pediatrics in the Division of Immunology and Rheumatology and medical director of the UCSF Clinical and Translational Science Institute (CTSI) Pediatric Clinical Research Center. Dr. Puck’s research is in human primary immunodeficiencies. Her scientific contributions include mapping and identification of the genes for X-linked severe combined immunodeficiency (XSCID) and autoimmune lymphoproliferative syndrome (ALPS), completion of a clinical trial of retroviral gene therapy for patients with XSCID who failed bone marrow transplantation, and definition of the disease and gene defects in STAT3 in hyper-IgE syndrome (Job's syndrome), a multisystem disorder. On the translational side, she has developed a test to screen all newborns for severe lymphocyte disorders and is planning a large pilot trial. Dr. Puck also uses mouse models to probe lymphocyte development and is investigating a new gene identified by her lab that, when knocked out, results in arrest of T-cell development from common lymphoid presursors.
Dr. Puck’s program focuses on human primary immunodeficiencies, diseases that are pleiotropic in phenotype and rare, but treatable. They are important because they illuminate generalizable mechanisms in human host defenses and autoimmunity that often differ from predictions based on targeted gene disruptions in mice. Projects include investigation of genetics, clinical and molecular characterization, and management of selected primary immunodeficiencies. Studies in humans are augmented with mouse models to advance basic understanding and develop therapies, including hematopoietic stem cell gene therapy. Documentation and scoring of clinical features of selected diseases has been a starting point for experiments to probe linkage and underlying molecular mechanisms. The overarching goal is to return to the clinic with new approaches for population screening, specific diagnosis, identification of genetic modifiers, and treatment.
Severe combined immunodeficiency (SCID) is a major topic of research in the laboratory. In 1993, Dr. Puck’s group and another laboratory independently identified the X-linked SCID disease gene, accounting for 50% of all cases, as the common gamma chain cytokine receptor; now 14 SCID genes are known, but details of pathogenesis and genotype/phenotype correlations remain to be fully worked out. Individuals with SCID are healthy at birth, but die of infections in infancy unless provided with a functional immune system. Bone marrow transplantation, enzyme replacement, and even gene therapy have changed this previously fatal disease to a treatable one. SCID infants identified by a prior family history and treated early in life have better survival, less morbidity and lower treatment costs than those recognized only after onset of serious infections. Unfortunately, most infants with SCID today are not identified in the pre-infectious period. Universal newborn screening could remedy this problem. T-cell receptor excision circles (TRECs) can be quantitated in the dried blood spots already collected from all babies, and babies with SCID lack TRECs. TREC newborn screening is being pursued to identify SCID cases in time for pre-symptomatic treatment and also afford opportunities to (1) investigate all causes of absent TRECs; (2) learn the true incidence of SCID; (3) find additional SCID genes; and (4) discover correlations between clinical features and particular geneotypes. This information in turn could lead to optimization of treatment, including implementation of gene targeted therapies.
Dr. Puck has also worked to define other human primary immunodeficiencies, including autoimmune lymphoproliferative syndrome (ALPS), due to defects in lymphocyte apoptosis, and hyper-immunoglobulin E syndrome (HIES or Job syndrome). The variable expressivity and penetrance of these disorders provides a challenge to discover genetic modifiers using genomic technologies in combination with rigorous clinical scoring of large patient and family cohorts.