Kasturi Haldar, PhD Professor Pathology and Microbiology-Immunology Regulation of pathogenic vacuoles Curricula: Cell Biology Immunology and Microbial Pathogenesis E-mail:   k-haldar@northwestern.edu

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. Over the past ten years, my laboratory has investigated the human malaria parasite Plasmodium falciparum, a protozoan which invades and develops in red blood cells. Recently, we have also begun 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.

The central questions in the malaria research focus on two unique secretory organelles. The first is a vacuolar network of tubovesicular membranes that provides nutrients to the parasite. The second is an ‘apicoplast’ that is a secondary endosymbiont and relic chloroplast which nonetheless retains its plastid genome.

We also interested in microbial genes that 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 pathogens we use emerging genetic techniques in the development of functional assays to exploit the wealth of information that has emerged from genomics studies. To this end we ‘mine’ databases for functional motifs for unique organelles, develop high throughput assays and use microarrays to track global changes in secretory gene expression during intracellular pathogen development.

The work should define unique and fundamental secretory mechanisms exploited by diverse micro-organisms, that may provide new targets for immunological prophylaxis and/or chemotherapy.

Publications:

Harrison, T., Samuel, B., Akompong, T., Hamm, H., Narla, M., Lomasney, J., Haldar, K. (2003) Erythrocyte G protein coupled receptor signaling in malarial infection.  Science Sept 19th issue in press.

Lopez-Estrano, C., Bhattacharya, S., Harrison, T. and Haldar, K. (2003) Coperative domains define a unique host cell targeting signal in P. falciparum-infected erythrocytes.  Proc. Natl. Acad. Sci. USA in press.

Hiller, N.L., Akompong, T., Morrow, J., Holder, A. A., Haldar, K. (2003) Identification of a stomatin orthologue in vacuoles induced in human erythrocytes by malaria parasites: a role for microbial raft-proteins in apicomplexan vacuole biogenesis.  J. Biol. Chem. in press

Nawabi, P., Lykidis, A. Ji, D. D. and Haldar, K. (2003). Neutral lipid analysis reveals elevation of acylglycerols and lack of cholesterol esters in P. falciparum-infected erythrocytes.  Eukaryotic Cell in press.