Research Scientist, Chemistry at Carnegie Mellon University
Assistant Research Professor of Infectious Diseases and Microbiology at University of Pittsburgh (Adjunct Faculty)
The Chakrabarti group focuses on understanding: (1) the mechanism which maintains the fidelity of genome replication, particularly, replication at chromosome ends (telomeres). In this project we dissect the telomerase RNA mediated molecular pathways that contribute to telomere replication and genome maintenance; and (2) small RNA mediated gene regulation in human pathogens causing parasitic infections.
RNA mediated gene regulation has taken a central place in almost all eukaryotes and pathogenic protozoa are no exception. we employ integrative analysis of genome wide high-throughput RNA sequencing (RNA-seq), quantitative mass spectrometry combined with genetic and functional assays to infer biologic contexts of disease development. Particularly we are interested in elucidating the composition and mechanism of function of the small RNA regulatory complexes in clinically important parasitic protozoa Plasmodium falciparum and Trypanosoma brucei.
For this work, we collaborate with Dr. Mike Widom for computational analysis of high-throughput RNA sequencing, Dr. Subha Das for developing chemical tools to capture small RNA-protein complexes and Dr. Peter Yau (University of Illinois Urbana-Champaign, Biotechnology) for Mass Spectrometry analysis. Additionally, we are now able to characterize the structure and function of telomerase RNA from a genetically amenable vertebrate pathogen, Trypanosoma brucei. Since majority of the virulence genes in parasites are expressed from subtelomeric loci, we envision this study to be a steppingstone for our ongoing work on understanding the fidelity of telomere replication, genome maintenance and regulation of virulence properties in parasites. For this work, we collaborate with Dr. Bruce Armitage and Dr. Danith Ly to design and employ PNAs to capture and characterize P. falciparum telomerase and with Dr. Bibo Li (Cleveland State University, Biological Sciences) to genetically characterize the telomerase of T. brucei. Thus, my overall goal in CNAST is to develop an exciting research program focusing on pathogen genomics, RNA metabolism, and host-pathogen interactions which should ultimately facilitate drug development against these deadly human pathogens.
Sandhu, R.; Sanford, S.; Basu, S.; Park, M.; Pandya, U.M.; Li, B., Chakrabarti, K. A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei. Cell Research. 2013, 23(4):537-51.
Simoes-Barbosa, A.; Chakrabarti, K.; Pearson, M.; Benarroch, D.; Shuman, S.; Johnson, P.J. Box H/ACA snoRNAs are preferred substrates for the trimethylguanosine synthase in the divergent unicellular eukaryote T.vaginalis. RNA. 2012, 18(9):1656-65.
Ares. M. Jr.; Chakrabarti, K.; Stuttering against marginotomy. Nature Struct Mol Biol. 2008, 15(1):18-9.
Chakrabarti, K.; Pearson, M.; Grate, L.; Sterne-Weiler; T., Deans, J.; Donohue, J.P.; Ares, M. Jr. Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis. RNA. 2007, 13(11):1923-39.
Schiller, M.R.; Chakrabarti, K.; King, G.F., Schiller, N.I., Eipper, B.A., Maciejewski, M.W. Regulation of RhoGEF activity by intramolecular and intermolecular SH3 domain interactions. J Biol Chem. 2006, 281(27):18774-86.
Tse, M.T.*; Chakrabarti, K.*; Gray, C.; Chitnis, C.E.; Craig, A. Divergent binding sites on intercellular adhesion molecule-1 (ICAM-1) for variant Plasmodium falciparum isolates. Mol Microbiol. 2004, 51(4):1039-49. (Co-first Authors)