Laboratory of Clinical Microbiology and Immunology
John.Zabriskie@rockefeller.edu Pathogenic mechanisms of microbially induced autoimmune diseases.
Dr. Zabriskie’s lab is primarily interested in the development of a vaccine for the prevention of streptococcal infections using the group A streptococcal carbohydrate (Gr. A CHO) as an immunogen. Clinical studies with human sera containing anti-Gr. A CHO antibodies are opsonic for several different M+-specific strains, and this opsonic property can be absorbed by N-acetyl-glucosamine-tagged Sepharose beads. Animal studies show that by either passive immunization with anti-Gr. A CHO antibodies or active immunization with Gr. A CHO, mice can be protected from a lethal injection of group A streptococci of at least three different M+-specific strains. In addition, group A streptococcal oral colonization studies in mice have shown that oral immunization of mice with the Gr. A CHO prevents colonization of mice with live group A streptococci. Currently, the Zabriskie lab is repeating the oral colonization studies in chimpanzees, with administration of Gr. A CHO both orally and systemically prior to colonization with live group A streptococci.
A second project in the Zabriskie lab concerns protection of the host against the lethal effects of superantigen toxins, which bind to the lateral sides of the major histocompatibility complex and T cell receptor molecules rather than into the antigen-specific groove. This unique binding initiates a virtual explosion of the inflammatory cascade, and approximately 25 percent of all T cells may be stimulated at a given time, while conventional antigens trigger less than one percent. Previous work has shown that a single antipeptide antibody, prepared against two regions of amino acid sequence homology of the toxins, results in protection against lethal challenge with several different superantigen toxins. In addition, a smaller peptide of 12 amino acids also protects against lethal challenge when given one to two hours before superantigen administration. Single acid substitution experiments with the 12-mer peptide revealed that the first three amino acids, cysteine, methionine, and tyrosine, are responsible for the inhibitory effects. Tripeptides in their natural order, or reversed order, and both the D and L forms can also protect in an in vitro proliferation assay. Dr. Zabriskie’s current studies concentrate on determining whether it is the antibodies to these tripeptides, or the peptides themselves, that are protective in a lethal shock model in mice.
Born in Switzerland, Dr. Zabriskie completed his B.A. at Princeton University in 1951. He received his M.D. from the Columbia University College of Physicians and Surgeons in 1955. From 1955 to 1957 he was an intern and assistant resident in pediatrics at Bellevue Hospital before serving in the United States Air Force in France from 1957 to 1959. After a year as senior resident at the Babies Hospital, Dr. Zabriskie came to Rockefeller in 1960 as guest investigator and assistant physician. He became assistant professor in 1962, associate professor with tenure in 1968, and head of laboratory in 1993.