Research Bio
EVOLUTION OF IMMUNE SURVEILLANCE,
TUMOR AND VIRAL IMMUNITY
The overall goal of our research is to understand the co-evolutionary relationships between the structure of selected molecules (e.g., heat shock proteins [hsps], hsp-receptors [CD91], NK cell receptors [KIR, FcRs], non-classical class Ib molecules [XNCs]) and their functions in innate and adaptive immunity against tumors and viruses using the frog Xenopus laevis as animal model.
One specific research area addresses the postulated dual role of the hsps gp96 and hsp70 in immunity. The comparative tumor-immunity model developed in Xenopus provides an alternative to mice in order to explore the ability of hsps to generate responses against tumors that have down-regulated their MHC class Ia molecules thereby escaping immune surveillance. To better reveal the respective role of classical and non-classical MHC class I genes in immune surveillance and T cell development, we are developing transgenesis strategies to modulate their expression in vivo by RNAi knockdown and induced transgene expression.
A second area concerns phylogenetic history and biological significance several immune receptor gene families (e.g., KIR, FcR-like) that appear to regulate leukocyte functions through integration of inhibitory and activating signals, by genomic and genetic approaches based on the recently fully sequenced genome of the X. laevis sister species Silurana (Xenopus) tropicalis.
A third research area concerns basic comparative and applied studies of viral pathogenesis and immunity in amphibians caused by Poxvirus-like Iridoviruses such as Frog virus 3 (FV3). Because of the threat of emerging wildlife viral diseases on global biodiversity, fundamental research on comparative viral immunity has become crucial. We have established Xenopus as an important experimental model to study the host defense and the pathogenesis of Iridovirus infection, and evaluate the contribution of immunocompromised animals in the dissemination of the diseases. We are also developing a method to knockout (KO) putative virulence genes by site-specific integration of a selectable fluorescent marker into the FV3 genome. Susceptible Xenopus larvae provide an ideal model to evaluate the impact of KOs on in vivo virus load, host mortality and the induction of pro-inflammatory genes.
Xenopus laevis Research Resource for Immunology: The University of Rochester is home to the world's most comprehensive resource specializing in the use of the amphibian Xenopus laevis for immunological research. Several genetically-defined inbred strains and clones are available for study. The facility also maintains and develops research tools such as transgenic animals, monoclonal antibodies, cell lines, DNA libraries and molecular probes. The resource includes a satellite facility devoted to study infectious diseases caused by Iridovirus. The resource is funded by the National Institutes of Health (NIAID).
