Dr. Kasturi Haldar
The Rev. Julius A. Nieuwland, C.S.C., Professor of Biological Sciences and the James C. Parsons and Carrie Ann Quinn Director of the Center for Rare and Neglected Diseases
Phone: (574) 631-1474
Understanding disease pathology and developing treatments in rare and neglected diseases.
Our goal is to convert research findings into therapeutics in rare, inherited disorders as well as neglected infectious diseases. These diseases have generally been ignored by the pharmaceutical industry because the financial rewards for developing new drugs and vaccines to treat them are so insignificant.
In rare diseases we focus on lysosomal disorders such as Niemann Pick Type C (NP-C) and Mucopolysaccharidosis Type III A (MPS IIIA), that result in neurodegenerative disease.
We have developed a quantitative, rapid neurobehavioural score by which to measure NP-C disease in mice. Using this scale, we are able to identify unique genetic signatures associated with disease progression, develop biomarkers as well as screen for drugs to treat disease in mice, in order that drugs can be progressed to clinical trials and therapeutic utilization. Parallel studies are underway with MPS IIIA.
We also study how lysosomal compartments in host cells move proteins and lipids to vacuoles of pathogens such as Salmonella. Our research has shown that when Salmonella infects human cells, it stimulates lipid accumulation in lysosomes by targeting a single host protein whose function is now being investigated in lysosomal rare diseases such as Niemann Pick Type C.
Finally, the laboratory has had a long standing interest in malaria. A major emphasis is the human malaria parasite Plasmodium falciparum, which invades and develops in red blood cells to cause disease pathologies that include severe malarial anemia and cerebral disease.
The overall goal is to define unique and fundamental mechanisms in mammalian cells as well as microorganisms, that provide molecular insights, targets and therapies in rare and neglected diseases.
To accelerate the development of therapies we partner with pharmaceutical companies in innovative models of private public partnerships. To this end we have recently signed a collaborative agreement with Eli Lilly & Co for drug discovery and development for Niemann Pick C disease and malaria.
1. Osborne AR, Speicher KD, Tamez PA, Bhattacharjee S, Speicher DW, Haldar K: The host targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum. Mol Biochem Parasitol 2010, 171(1):25-31.
2. Tamez PA, Liu H, Fernandez-Pol S, Haldar K, Wickrema A: Stage-specific susceptibility of human erythroblasts to Plasmodium falciparum malaria infection. Blood 2009, 114(17):3652-3655.
3. 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, 105(37):14141-14146.
4. Haldar K, Murphy SC, Milner DA, Taylor TE: Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease. Annu Rev Pathol 2007, 2 :217-249.
5. Haldar K, Kamoun S, Hiller NL, Bhattacharje S, van Ooij C: Common infection strategies of pathogenic eukaryotes. Nat Rev Microbiol 2006, 4 (12):922-931.
6. Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estrano C, Haldar K: A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science 2004, 306(5703):1934-1937.
7. Harrison T, Samuel BU, Akompong T, Hamm H, Mohandas N, Lomasney JW, Haldar K: Erythrocyte G protein-coupled receptor signaling in malarial infection. Science 2003, 301(5640):1734-1736.