Distinguished Lecture, Jeffrey V. Ravetch : Fc Receptors – Drivers of Immunity
Programme
10:30 | Opening remarks and introduction by Jules Hoffmann, Chair of Integrative Biology, USIAS |
10:40 | Lecture by Jeffrey V. Ravetch, Rockefeller University, US : |
11:40 | Discussion moderated by Jules Hoffmann |
Abstract
Fc Receptors – Drivers of Immunity
How do antibodies mediate diverse effector activities through an apparently invariant Fc domain?
The solution to this paradox is to be found in the diversity of receptors that engage the Fc domain, collectively called the Fcγ receptors. These cell surface receptors, selectively expressed on various immune cell populations, confer specificity on the IgG immune response by their selective engagement of Fcs that differ in subclass and glycan composition. The Fc domain thus displays a surprising degree of structural diversification enabling distinct structures to engage individual members of this extended family of receptors. Unique Fc structures and their cognate receptors have been defined that result in either pro-inflammatory, anti-inflammatory, or immunomodulatory activity of antibodies in vivo. These observations have provided a molecular explanation for the mechanisms by which antibodies can mediate their therapeutic or pathogenic activities and has resulted in in the development and approval of novel therapeutics for autoimmune, infectious and neoplastic diseases.
Jeffrey V. Ravetch
Jeffrey V. Ravetch, MD, PhD is the Theresa and Eugene Lang Professor at The Rockefeller University and Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology.
Professor Ravetch, a native of New York City, received his undergraduate training in molecular biophysics and biochemistry at Yale University and earned his BS degree in 1973 working with Donald M. Crothers on the thermodynamic and kinetic properties of synthetic oligoribonucleotides. He continued his training at The Rockefeller University – Cornell Medical School MD/PhD programme, earning his doctorate in 1978 in genetics with Norton Zinder and Peter Model, during which he investigated the genetics of viral replication and gene expression for the single stranded DNA bacteriophage f1. In 1979 he earned his MD from Cornell University Medical School. He pursued postdoctoral studies at the NIH with Phil Leder where he identified and characterised the genes for human antibodies and the DNA elements involved in switch recombination. From 1982 to 1996, Professor Ravetch was a member of the faculty of the Memorial Sloan-Kettering Cancer Center and Cornell Medical College.
Professor Ravetch and his team have focused on the Fc domain of antibodies and the receptors it engages, determining the mechanisms by which this domain enables antibodies to mediate their diverse biological activities in vivo. His work established the novel structural basis for Fc domain functional diversity and the pre-eminence of FcR pathways in host defense, inflammation and tolerance, describing novel inhibitory signaling pathways to account for the paradoxical roles of antibodies as promoting and suppressing inflammation. His studies have focused on the redesign of antibodies to enhance their therapeutic capacity for the treatment of autoimmune diseases like lupus and arthritis, as well as cancer and infectious diseases. His work has been widely extended into clinical applications for the treatment of neoplastic, inflammatory and infectious diseases.
Professor Ravetch has received numerous awards during his career, including the William B. Coley Award, Cancer Research Institute (2007), the Gairdner International Award (2012), the Sanofi-Institut Pasteur Award (2012) the Wolf Prize in Medicine (2015), the Ross Prize in Molecular Medicine (2017), and most recently, the Robert Koch Award (2018).