Research Interests
Immunity to Viral Infections and Cancers
A major interest in our laboratory is biology of Human Leukocyte Antigen (HLA) class I (HLA-I) molecules, which are critical for immune surveillance by CD8+ T cells and natural killer (NK) cells of the immune response. HLA-I molecules display viral and mutated peptides on the cell surface for recognition by antigen receptors of CD8+ T cells. The HLA-I genetic locus is the highly polymorphic. Generally, HLA-I assembly with peptides occurs in the endoplasmic reticulum (ER) of cells. Our laboratory is investigating unconventional HLA class I trafficking and assembly routes, particularly those within endo-lysosomal compartments, which could confer superior protective functions to certain HLA-I variants under specific pathological conditions. CD8 is a co-receptor for immune recognition of infected and cancer cells by CD8+ T cells and NK cells. We study variations in HLA class I-CD8 interactions and resulting functional effects on the immune response. We are also interested in factors that influence the diversity of peptides presented by a given HLA class I molecule (the peptidome).
Calreticulin in an ER chaperone that plays important roles in the folding of HLA-I molecules in the ER. Calreticulin itself becomes mutated in certain types of myeloproliferative neoplasms (MPN). Another major current interest in our laboratory relates to the molecular mechanisms of cell transformation by the MPN mutant calreticulin as well as immune recognition of cells expressing MPN mutant calreticulin.