Malini Raghavan

Malini Raghavan, Ph.D.

Professor of Microbiology and Immunology
Rackham Faculty Ally for Diversity in Graduate Education, Immunology Program Faculty Co-Representative
Interim Acting Director, Graduate Program in Immunology
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Malini Raghavan obtained her BS from the Women's Christian College in Chennai, India in 1983 and her MSc from the Indian Institute of Technology, Kanpur in 1985, doing research in organic chemistry in the laboratory of Dr. S Chandrasekaran. She came to the United States for her graduate studies, obtaining a PhD in Chemistry from Princeton University in 1991, following her thesis work in the laboratory of Dr. Clarence Schutt. She then did her postdoctoral training in Immunology at Caltech, in the laboratory of Dr. Pamela Bjorkman. She then joined the faculty of the University of Michigan, Department of Microbiology and Immunology in 1996, where she has since been.

Research Interests

Major Histocompatibility Complex (MHC) class I molecules are ligands for antigen receptors of CD8+ T cells and Natural Killer (NK) cells. Human MHC class I molecules are encoded by three sets of genes –the human leukocyte antigens (HLA-A, HLA-B and HLA-C). These genes are highly polymorphic, and particular alleles have profound influences on disease outcomes in infectious diseases, autoimmunity, transplantation and cancer. A major interest in our laboratory is in the HLA class I Antigen Processing and Presentation Pathway, the cellular pathway by which complexes of peptides and HLA class I molecules are generated and displayed on the cell surface for immune surveillance by CD8+ T cells and NK cells. Generally, HLA class I assembly with peptides occurs in the endoplasmic reticulum (ER) of cells. Our laboratory is investigating unconventional HLA class I assembly routes. Although cell-surface forms of HLA class I are generally peptide-bound, our recent studies indicate the prevalence of peptide-free (empty) HLA class I on the cell surface, enhanced for some allotypes. We study the functions of empty HLA class I molecules. We also study the relevance of HLA class I-CD8 interactions to the functions of different immune cell subsets. We are interested in factors that influence the diversity of peptides presented by a given HLA class I molecule (the peptidome).

Calreticulin in a ER chaperone that plays important roles in the folding of MHC class I molecules and a number of other glycoproteins. Our recent studies have defined the interactions of calreticulin with calcium, nucleotides and phospholipids and their functional effects upon MHC class I assembly and upon the phagocytosis of dying cells. Calreticulin itself becomes mutated in certain types of myeloproliferative neoplasms (MPN). A 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. We also study the molecular mechanisms by which calreticulin contributes to the maintenance of ER homeostasis under conditions where misfolded and insoluble glycoproteins accumulate.

Research Opportunities for Rotating Students