Signaling and trafficking mechanisms of pathogens and their mammalian hosts

Kasturi Haldar     Professor, Julius Nieuwland Chair of Biological Sciences Director, Center for Rare and Neglected Diseases University of Notre Dame   Office Phone: (574)631-1474 Center Phone: (574)631-3372 Center Fax: (574)631-9788 email: khaldar@nd.edu labpage: http://www.nd.edu/~haldarlb/ center webpage: http://www.nd.edu/~crnd/   Massachusetts Institute of Technology (PhD; Biochemistry)   Site of Fellowship Rockefeller University

e-mail | labpage

Research Interests

Regulation of pathogenic vacuoles and their links to disease.   The secretory pathway delivers proteins and lipids to organelles to support the growth of their membranes in a eukaryotic cell. My interests lie in studying how this pathway interacts with vacuoles of intracellular pathogens. My laboratory has investigated the human malaria parasite Plasmodium falciparum, a protozoan which invades and develops in red blood cells. We are also studying how the secretory and endo-vacuolar pathways of epithelial cells and macrophages move proteins and lipids to vacuoles of pathogens such as Salmonella, Mycobacteria, Chlamydia and Toxoplasma. My long-term objectives are to understand the common principles of vacuolar biogenesis of emerging and re-emerging infections and their links to chronic disease pathologies in animal models and human populations. The central questions in the malaria research focus on two unique, secretory functions. The first is a vacuolar network of tubovesicular membranes that provides nutrients to the parasite and thus provides novel drug targets. The second is a 'secretome' of about four hundred genes that remodel the host cell and are linked to virulence and disease.   We also interested in microbial genes that engage in molecular mimicry to regulate the trafficking/signaling of vacuoles containing pathogens such as Salmonella, Chlamydia, Mycobacteria and Toxoplasma in mammalian epithelial cells and/or macrophages. For all of these host-pathogen interactions we use emerging genetic techniques and functional assays to exploit the wealth of information that has emerged from genomics studies. To this end we ‘mine’ databases for functional motifs, develop high throughput assays and use proteomics and microarrays to track global changes in secretory gene expression. The work has defined unique and fundamental secretory mechanisms in host cells as well as micro-organisms, that provide molecular insights and targets in inherited diseases (such as lysosomal disorders) as well as infectious diseases (malaria and gastroenteritis).

Selected Publications

Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estraño C, Haldar K. A host-targeting signal in virulence proteins reveals a secretome in malarial infection.  Science. 2004 Dec 10;306(5703):1934-7.

Haldar K, Kamoun S, Hiller NL, Bhattacharje S, van Ooij C. Common infection strategies of pathogenic eukaryotes. Nat Rev Microbiol. 2006; 4:922-931.

Haldar K, Murphy SC, Milner DA, Taylor TE. Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease. Annu Rev Pathol. 2007;2:217-49.

Jackson LK, Nawabi P, Hentea C, Roark EA, Haldar K. The Salmonella virulence protein SifA is a G protein antagonist. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14141-6.

Nawabi P, Catron DM, Haldar K.  Esterification of cholesterol by a type III secretion effector during intracellular Salmonella infection. Mol Microbiol. 2008 Apr;68(1):173-85.