Diagnostic platform for neglected diseases
Deciphering virulence determinants in infectious disease causing pathogens represent only half the battle. These diseases are often branded as “neglected” because of lack of proper diagnostic toolkits for early detection. However, timely diagnosis is the key to correct treatment. Our group therefore also strives to translate the scientific know how into reliable diagnostic tests based upon various immunological and molecular biology techniques. We offer free services to hospitals, animal farms and similar organizations to screen a panel of both human and veterinary infections.
Our current diagnostic landscape includes:
Detection of Trypanosoma evansi infection in horses by ELISA.
Screening of Babesia and Theleria infections in cattle by PCR.
Accurate species identification of Candida clinical isolates from patients by PCR.
Drug development for neglected diseases
Our translational portfolio also covers elucidation of new drug targets and drug development for protozoan parasites. Extensive research in the lab has shown that heat shock protein 90, Hsp90, a key molecular chaperone is essential for the growth of protozoan parasites. Using a semisynthetic Hsp90 inhibitor, namely 17-(allylamino)-17-demethoxygeldanamycin, it was shown that Hsp90 inhibition is effective in attenuating parasite growth and prolonging survival in a rodent model of malaria and trypanosomiasis. Therefore, we are exploring the potential of exploiting Hsp90 as a broad-spectrum target for treatment of infectious diseases. Since Hsp90 inhibitors are already under advanced stage clinical trials for cancer treatment, repurposing these drugs to treat infectious diseases seems to be a promising therapeutic strategy Potential of Hsp90 as anti-infective has been seen in the following infections in our laboratory:
Ring to trophozoite stage inhibition in P. falciparum
(Banumathy G., Singh V., Pavithra S. R., Tatu U. (2003). Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. J. Biol. Chem.)
Attenuation of parasite growth in mouse model of malaria
(Pallavi R, Roy N, Nageshan RK, Talukdar P, Pavithra SR, Reddy R, Venketesh S, Kumar R, Gupta AK, Singh RK, Yadav SC, Tatu U. Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug. J Biol Chem. 2010 Dec 3;285(49):37964-75)
Potent inhibition of T. evansi growth in mice modelRochani A. K., Mithra C., Singh M., Tatu U. (2014). Heat shock protein 90 as a potential drug target against surra. Parasitology 141 1148–1155. 10.1017/S0031182014000845)
Growth arrest and encystation in Giardia lamblia
(Nageshan RK, Roy N, Ranade S, Tatu U. Trans-spliced heat shock protein 90 modulates encystation in Giardia lamblia. PLoS Negl Trop Dis. 2014 May 1;8(5):e2829)
Growth arrest and encystation in Entamoeba histolytica
Singh, M., Sharma, S., Bhattacharya, A., & Tatu, U. (2015). Heat Shock Protein 90 regulates encystation in Entamoeba. Frontiers in Microbiology, 6, 1125
Essential for growth in Theileria annulata
(Kinnaird, J. H., Singh, M., Gillan, V., Weir, W., Calder, E. D. D., Hostettler, I., Tatu, U., Devaney, E., and Shiels, B. R. (2016) Characterization of HSP90 isoforms in transformed bovine leukocytes infected with Theileria annulata. Cellular Microbiology, doi: 10.1111/cmi.12669)
Design of first peptide based Hsp90 inhibitor
(Raman, S., Singh, M., Tatu, U., Suguna, K. (2015). First Structural View of a Peptide Interacting with the Nucleotide Binding Domain of Heat Shock Protein 90. Sci Rep. 2015 Nov 24;5:17015.)