Biography

Malaria afflicts about half of the world population causing over 600,000 deaths each year. In addition to contributing significantly towards overall childhood mortality in the poorest nations, the disease is estimated to cause considerable reductions in the economic growth of countries that bear a heavy malaria burden. The situation is made worse because the widespread prevalence of drug-resistant parasites is rendering the limited number of available drugs less effective for clinical use. Therefore, there is a pressing need for novel therapeutic options to treat multidrug resistant malaria. It is also important to understand the molecular mechanism of parasite growth and differentiation so that novel therapeutic targets can be identified.

A major focus of my research program is to identify next-generation antimalarial compounds from both natural products and synthetic libraries residing in druggable chemical space. To pursue this goal, we have successfully concluded screening of >5,000 marine macro- and micro- organism and > 10,000 fungal extract libraries. Dereplication of active extracts has led to the identification of many unique antiplasmodial scaffolds and the work has resulted in issued US patents. In vitro evolution of resistance followed by whole genome sequence analysis has led to the identification of molecular targets of the identified scaffolds. Another aspect of research in my laboratory focuses on repurposing cancer drugs for malaria therapies. In this endeavor, we have utilized type II scaffolds targeting human protein kinases to identify multi-stage active antimalarials.

Recent Publications

1. Jiang, T., Lee, J.W., Collins, J.E., Schaefer, S., Chen, D., Nardella, F., Wendt, K., Peramuna, T.G., Paes, R., McLellan, J.L., Bhasin, J., Durst, G.L., Hanson, K., Chakrabarti, D., Cichewicz., Winzeler, E.A. (2024) Fungal derived methyldeoxyphomins target Plasmodium falciparum segregation through the inhibition of PfActin1. Accepted for publication in PNAS.
2. Schulz, D.C., Chávez-Riveros, A., Goertzen, M.G., Brummel, B.R., Paes, R., Santos, N.M., Tenneti, S., Abboud, K.A., Rocca, J.R., Seabra, G., Li, C., Chakrabarti, D., Huigens, R.W. (2024) Chloroformate-mediated ring cleavage of indole alkaloids leads to re-engineered antiplasmodial agents. Org. Biomol. Chem. Doi:10.1039/d4obob00853g. PMID: 39113550
3. Collins, J.E., Jiang, T., Lee, J.W., Wendt, K.L., Nardella, F., Jeon, J., Paes, R., Santos, N.M., Rocamora, F., Chang, M., Schaefer, S., Cichewicz, R., Winzeler, E.A., Chakrabarti, D. (2024) Understanding the antiplasmodial action of resistant refractory Xanthoquinodin A1. ACS Infect Dis 10:2276-2287. Doi:10.1021/acsinfecdis.4c00232. PMID: 38810215
4. Jiang, T., Godinez-Macias, K.P., Collins, J.E., Lee, J.W., Wendt, K.L., Carolino, K., Chakrabarti, D., Cichewicz, R.H., Winzeler, E.A. (2024) Identification of fungal natural products with potent inhibition in Toxoplasma gondii. Microbiol Spectr. 12:e0414223. doi: 10.1128/spectrum.04142-23. PMID: 38421191
5. Wang, L*., Bohmer, M*, Wang, J., Calla, J., Nardella, F., Schindler, K., Pazicky, S., Tumwebaze, P., Rozenthal, P., Bozdech, Z., Chakrabarti, R., Cooper, R., Desai, S., Winzeler, E., Chakrabarti, D.*, Gray, N.* (2023) Co-corresponding author. Discovery of Potent Antimalarial Type II kinase inhibitors with selectivity over human kinases.  Med.Chem 67:1460-1480 doi: 10.1021/acs.jmedchem.3c02046 PMID: 38214254
6. Rayala, R., Chaudhuri, P., Bunnell, A., Roberts, B., Chakrabarti D., Nefzi, A. (2023) Diversity oriented synthesis of piperizine tethered thiazole compounds with antiplasmodial activity. Int J. Mol. Sci. 12;24:17414. Doi: 10.3390/ijms2425417414. PMID:38139243
7. Collins, J.E., Lee, J.W., Rocamora, F., Saggu, G.S., Wendt, K.L., Santos, N, Paes, R., Hanson, K. Niles, J.C., Desai, S.A., Winzeler, E.A., Cichewicz, R.H., Chakrabarti, D. (2023) Antiplasmodial peptaibols act through membrane directed mechanisms. Cell Chem. Biol. doi.org/10.1016/j.chembiol.2023.10.025. PMID: 37995692
8. Chakrabarti, D. and Doerig, C. (2023) Editorial Overview: Recent advances in fundamental and translational research on parasitic protists Curr. Opin. Microbiol. 75: 102360. doi: 10.1016/j.mib.2023.102360. PMID: 37467615
9. Lee, J.W., Collins, J.E., Hulverson, M.A., Aguila, L.K.T., Kim, C.M., Wendt, K.L., Chakrabarti, D., Ojo, K.K., Wood, G.E., Van Voorhis, W.C., Cichewicz, R.H. (2023) Appraisal of fungus-derived xanthoquinodins as broad-spectrum anti-infectives targeting phylogenetically diverse human pathogens. J. Nat. Prod. 86: 1596-1605. doi:10.1021/acs.jnatprod.3c00283. PMID:37276438.
10. Bohmer, M.J., Wang, J., Istavan, E.S., Luth, M.R., Collins, J.E., Huttlin, E.L., Wang, L., Mittal, N., Hao, M., Kwiatkowski, N.P., Gygi, S.P., Chakrabarti, R., Deng, X., Goldberg, D.E., Winzeler, E.A., Gray, N.S., D. (2023) Human polo-like kinase inhibitors as antiplasmodials. ACS Infect. Dis. 9:1004-10021. doi: 10.1021/acsinfecdis.3c00025. PMID: 36919909.
11. Iyamu, I.D., Zhao, Y., Parvatkar, P.T., Roberts, B.F., Cassandra, D.R., Wojtas, L., Kyle, D.E., Chakrabarti, D., Manetsch, R. (2022) Structure-activity and structure-property relationship studies of spirocyclic chromanes with antimalarial activity. Biorg Med Chem 57:116629. doi: 10.1016/j.bmc.2022.116629. PMID: 35091169.
12. Collins JE, Lee JW, Bohmer MJ, Welden JD, Arshadi AK, Du L, Cichewicz RH, Chakrabarti D. (2021) Cyclic Tetrapeptide HDAC inhibitors with improved Plasmodium falciparum selectivity and killing profile. ACS Infect Dis. 7: 2889-2903. doi: 10.1021/acsinfecdis.1c00341. PMID: 3441031