The Malini Raghavan Research Group

We are a group of interdisciplinary scientists who seek to understand the assembly pathways of major histocompatibility complex (MHC) class I molecules and how genetic variations in the human MHC (also called human leukocyte antigens (HLA)) class I affect immunity to virus infections. HLA class I molecules bind to intracellular peptides and present these peptides to cytotoxic T cells, which recognize and kill virus-infected cells and tumor cells. HLA class I molecules also regulate the functional activities of natural killer (NK) cells of the immune response. We study the molecular mechanisms of function of factors relevant to the assembly of HLA class I molecules with peptides. We also study how HLA class I variants differ in their assembly characteristics, and how such differences affect immunity and disease outcomes.

Another major goal in our laboratory is to understand the functions of calreticulin, a chaperone of the endoplasmic reticulum (ER). A number of protein folding diseases arise from the misfolding of glycoproteins in the ER. One example is alpha1-antitrypsin (AAT)-deficiency, a genetic disorder that arises from the presence of misfolded variants of AAT. Calreticulin controls the folding, secretion and solubility of many glycoproteins including MHC class I molecules and AAT. Additionally, calreticulin itself is mutated in myleoproliferative neoplasms, and the mutations are predicted to affect the innate and adaptive immune functions of calreticulin. We study many of these aspects of calreticulin biology, with relevance to health and disease.