1979-1980 Teaching Assistant, Washington University, St. Louis, MO
1985-1989 Guest Researcher, Laboratory of Immunology NIAID, NIH
1989-1997 Assistant Professor, University of Chicago, Department of
1997-2002 Associate Professor, University of Chicago, Department of
2002-Current Professor, University of Rochester Medical School,
Department of Microbiology and Immunology
Specific Areas of Research Interest
The defining feature of the immune system is its ability to distinguish self from non-self. The major component of the immune system responsible for this self / non-self discrimination is the diverse repertoire of antigen-specific T lymphocytes. T cell receptors can only recognize antigens derived from pathogens or transformed cells if these antigens if the derived peptide fragments of pathogenic protieins combine with Major Histocompatibility Complex (MHC) molecules. The assembly of the antigenic peptide-MHC complex takes place in intracellular compartments, by a series of molecular events collectively referred to as "MHC-restricted antigen presentation". The research in my laboratory centers around the molecular events that regulate MHC class II-restricted antigen presentation and CD4 T cell activation in vivo. Our long term goal is to make connections between the mechanisms involved in peptide acquisition by class II molecules and those aspects of immunology that critically depend on the specific peptides presented by the class II molecule.
Specific Areas of Research Interest
1. Immunodominance in CD4 T cell responses. In specific immune responses pathogens or to protein antigens, T lymphocytes only respond to a limited number of peptide epitopes from the immunogens. These peptides are termed "immunodominant". Our experiments seek to understand the elements in vivo that dictate the narrowed selection of specificities in CD4 T cells during protective immune response, particularly pathogens such as influenza virus. One of our long-term goals is to apply the knowledge gained in animal models towards human vaccine design.
2. CD4 T cell response to influenza virus. One of our more recent areas of research is the antigen specificity and role that CD4 T cells play in the protective immune response to influenza virus. One of the major challenges in vaccine design for this pathogen is the high degree of genetic variability that occurs in different isolates, making most currently vaccines protective for only a short period of time, until a new influenza strain become prevalent in the population. Our interests focus on efforts to promote heterosubtypic immunity in the CD4 T cell compartment, by developing strategies to focus the CD4 T cells towards the most biologically active and genetically conserved epitopes.
3. Role of DM in regulating class II-restricted antigen presentation. The MHC-encoded DM molecule is now known to be a critical component of the class II presentation pathway by acting as a catalyst for peptide loading and for editing the peptide repertoire presented by class II molecules on antigen presenting cells. Our studies are aimed at understanding the molecular basis of such peptide discrimination by DM proteins and how they influence CD4 T cell activation and tolerance.
4. Molecular basis for MHC-linked autoimmunity. Genetically-determined susceptibility to autoimmune diseases is frequently associated with the expression of particular MHC class II gene products. Our laboratory is focused on delineating the structural features of MHC molecules that defects in self tolerance and induction of autoimmunity and the role that B cells play as antigen presenting cells during the induction and amplification of autoimmune responses