Kasturi Haldar, the Julius Nieuwland Professor of Biology and Parsons-Quinn Director for the Center for Rare and Neglected Diseases at the University of Notre Dame is an authority on the mechanisms by which human malaria parasites remodel their host cells. Her laboratory pioneered the application of modern cell biological tools to studying malarial infection of the erythrocyte. They identified a novel transport signal that enables parasite protein to access the host erythrocyte and thus defined secretome of several hundred parasite effectors involved in virulence and structural remodeling of the host. Other major achievements include the identification of the pathway of parasite protein export to the erythrocyte and demonstration that the host targeting signal of malaria parasites is shared by the Irish potato famine pathogen Phytophthora infestans.
The Haldar lab also identified novel malarial Golgi dynamics that underlie a lipid rich, nutrient import pathway in infected erythrocytes and enable transport of cholesterol-rich host 'raft' complexes, essential nutrient solutes and lipids to the malarial vacuole. They have further established that the sterol biosynthetic pathway and cholesterol are important to intracellular infection by Salmonella.
In addition, Haldar and her colleagues have shown that adrenergic signaling is an active process in erythrocyte and required for malaria invasion and growth. They have established erythrocyte signaling pathways can be targets for malarial infection and may be important for treatment of malaria.
- B.Sc., Bryn Mawr College
- Ph.D., Biochemistry, Massachusetts Institute of Technology
- Postdoctoral Fellow, Rockefeller University
Awards and Honors
- Elected Fellow, American Academy of Microbiology
- Elected Fellow, American Academy for the Advancement of Science
- Burroughs Wellcome Fund, New Investigator Award and New Initiatives in Malaria Award
- Safeukui I, Gomez ND, Adelani AA, Burte F, Afolabi NK, Akondy R, et al. (2015) Malaria Induces Anemia through CD8+ T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen. mBio 6(1):e02493-14
- Jauréguiberry S, Ndour PA, Roussel C, Ader F, Safeukui I, Nguyen M, et al. (2014) Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins. Blood 124(2):167-75
- Bhattacharjee S, Stahelin RV, Speicher KD, Speicher DW, Haldar K (2012) Endoplasmic Reticulum PI(3)P lipid binding targets malaria proteins to the host cell. Cell 148(1-2):201-212
- Tamez PA, Liu H, Fernandez-Pol S, Haldar K, Wickrema A (2009) Stage-specific susceptibility of human erythroblasts to Plasmodium falciparum malaria infection. Blood 22;114(17):3652-5
- van Ooij C, Tamez P, Bhattacharjee S, Hiller NL, Harrison T, Liolios K, et al. (2008) The malaria secretome: from algorithms to essential function in blood stage infection. PLoS Pathog 4(6):e1000084
- Tamez PA, Bhattacharjee S, van Ooij C, Hiller NL, Llinás M, Balu B, et al. (2008) An Erythrocyte Vesicle Protein Exported by the Malaria Parasite Promotes Tubovesicular Lipid Import from the Host Cell Surface. PLOS Pathog 4(8):e1000118.
- Bhattacharjee S, Hiller NL, Liolios K, Win J, Kanneganti TD, Young C, Kamoun S, Haldar K (2006) The malarial host-targeting signal is conserved in the Irish potato famine pathogen. PLOS Pathog 2(5):e50
Michael Malim is currently Head of the School of Immunology & Microbial Sciences and Professor of Infectious Diseases, King’s College London, as well as Director of the MRC Doctoral Training Partnership in Biomedical Sciences and Theme Lead for Infection and Immunity in the Biomedical Research Centre at Guy’s & St Thomas’ NHS Foundation Trust & King’s College London. Since 2018, he has been Vice President (Non-Clinical) at the Academy of Medical Sciences.
He was previously a faculty member in the Departments of Microbiology and Medicine at the University of Pennsylvania.
Malim’s laboratory works on the molecular pathogenesis of virus infections of importance to global health, particularly HIV-1 and influenza A virus, and embraces a broad range of molecular genetic, cultured cell, biochemical, structural, bioinformatic and cohort-based methods to explore the fundamental principles of virus replication and host-mediated control. One long-running topic of interest has been the HIV-1 non-structural protein, Vif. This led to the identification of the human protein APOBEC3G as an anti-viral effector specifically antagonised by Vif, and revealed a novel form of innate immunity involving the destructive editing of viral DNA.
Before becoming joint Editor-in-Chief for PLOS Pathogens in 2019, Malim served as a Section Editor after joining the Editorial Board in 2004. He also serves as an Editor for Virology.
- B.Sc., Biochemistry, University of Bristol
- D. Phil, Biochemistry, University of Oxford
Awards and Honors
- Elizabeth Glaser Pediatric AIDS Foundation Scientist Award
- KT Jeang Retrovirology Prize
- Elected, Fellow of the Academy of Medical Sciences
- Elected, Member of the European Molecular Biology Organisation
- Elected, Fellow of the American Academy of Microbiology
- Elected, Fellow of the Royal Society
- Jimenez-Guardeño, J.M., Apolonia, L., Betancor, G. and Malim, M.H. (2019). Immunoproteasome activation enables human TRIM5a restriction of HIV-1. Nature Microbiology 4, 933-940
- Dicks, M.D.J., Betancor, G., Jimenez-Guardeño, J.M., Pessel-Vivares, L., Apolonia, L., Goujon, C., and Malim, M.H. (2018). Multiple components of the nuclear pore complex interact with the amino-terminus of MX2 to facilitate HIV-1 restriction. PLoS Pathogens 14, e1007408
- Doyle, T., Moncorgé, O., Bonaventure, B., Pollpeter, D., Lussignol, M., Tauziet, M., Apolonia, L., Catanese, M.-T. Goujon, C. and Malim, M.H. (2018). The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry. Nature Microbiology 3, 1369-1376
- Goujon, C., Moncorgé, O., Bauby, H., Doyle, T., Ward, C.C., Schaller, T., Hué, S., Barclay, W.S., Schulz, R. and Malim, M.H. (2013). Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature 502, 559-562
- Sherer, N.M., Swanson, C.M., Hué, S., Roberts, R.G., Bergeron, J.R.C. and Malim, M.H. (2011). Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication. PLoS Pathogens 7, e1002395.
- Harris, R.S., Bishop, K.N., Sheehy, A.M., Craig, H.M., Petersen-Mahrt, S.K., Watt, I.N., Neuberger, M.S. and Malim, M.H. (2003). DNA deamination mediates innate immunity to retroviral infection. Cell 113, 803-809
- Sheehy, A.M., Gaddis, N.C., Choi, J.D. and Malim, M.H. (2002). Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418, 646-650