Post doctoral University of California, Los Angeles PhD Sloan Kettering Cancer Center, Cornell University BSc. University of Colombo, Sri Lanka

An important way that cells respond to environment is by controlling gene expression and in turn protein expression. The splicing of mRNA intermediates is an important mechanism for cells to control development and respond to changes in the environment. Changes in splicing events lead to neurologic disease and cancer. RNA binding proteins that function as splicing regulators tightly controls the process of splicing. Modifications of these proteins such as the addition of a phosphate or acetyl group leads to changes in the proteins' activity and concentration. This in turn generates mRNA isoforms and protein variants including those related to disease states. The Polypyrimidine Tract Binding Protein 1 (PTBP1) is an RNA binding protein controlling the splicing of many mRNA intermediates including those involved in cancer. My research group is studying PTBP1 to understand how the proteins' activity is altered by post-translational modifications.

Keppetipola N, Sharma S, Li Q, and Black DL. (2012) “Neuronal regulation of Pre-mRNA Splicing by Polypyrimidine Tract Binding Proteins, PTBP1 and PTBP2” Crit Rev Biochem Mol Biol. 47(4):360-78. PMCID: PMC3422667 Keppetipola N, Jain R, Meineke B, Diver M, and Shuman S. (2009)“Structure-activity relationships in Kluyveromyces lactis gamma-toxin, a eukaryal tRNA anticodon nuclease.” RNA 15, 1036-44. PMCID: PMC2685522 Keppetipola N, and Shuman S. (2008) “A phosphate-binding histidine of binuclear metallophosphodiesterase enzymes is a determinant of 2',3' cyclic nucleotide phosphodiesterase activity” J. Biol. Chem. 283, 30942-9. PMCID: PMC2576524 Keppetipola N, and Shuman S. (2007) “Characterization of the 2’, 3’ cyclic phosphodiesterase activities of Clostridium thermocellum polynucleotide kinase-phosphatase and bacteriophage lambda phosphatase” Nucleic Acids Res. 35, 7721-32. PMCID: PMC2190708 Keppetipola N, Nandakumar J, and Shuman S. (2007) “Reprogramming the end healing pathway of a bacterial RNA repair enzyme.” Nucleic Acids. Res.35, 3624-3630. PMCID: PMC1920235 Keppetipola N, Jain R, and Shuman S. (2007). "Novel triphosphate phosphohydrolase activity of Clostridium thermocellum TTM, a member of the triphosphate tunnel metalloenzyme superfamily" J. Biol. Chem. 282, 11941-9. PMID: 17303560 Keppetipola N, and Shuman S. (2006). "Distinct enzymic functional groups are required for the phosphomonoesterase and phosphodiesterase activities of Clostridium thermocellum polynucleotide kinase-phosphatase." J. Biol. Chem. 281, 19251-19259. PMID: 16675457 Keppetipola N, and Shuman S. (2006). "Mechanism of the phosphatase component of Clostridium thermocellum polynucleotide kinase-phosphatase." RNA 12, 73-82. PMCID: PMC1370887 Keppetipola N, and Shuman S. (2005). "Characterization of a thermophilic ATP-dependent DNA ligase from the euryarchaeon Pyrococcus horikoshii." J. Bacteriol. 187, 6902-8. PMCID: PMC1251619