Dr. Niroshika Keppetipola, Chemistry and Biochemistry

Education and Professional Positions

PhD. Sloan Kettering Cancer Center, Cornell University, New York
Post doctoral, University of California, Los Angeles
Assistant Professor, California State University at Fullerton

Current Research Interests

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 on 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. In addition to its role as a splicing regulator, PTBP1 plays a role in mRNA 3’ end processing, mRNA stability and IRES mediated translation. PTBP1 has many post-translational modifications but the role of most of these modifications are not understood. We are using PTBP1 as a model system to understand how modifications at specific amino acid side chains alter the splicing activity of the protein. Our experiments use a variety of molecular biology and biochemistry techniques both in vivo and in vitro.

Five publications related to current research interests

  1. 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
  2. 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
  3. 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
  4. 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
  5. Keppetipola N, and Shuman S. (2006). “Mechanism of the phosphatase component of Clostridium thermocellum polynucleotide kinase-phosphatase.” RNA 12, 73-82. PMCID: PMC1370887

Recent Student Awards

2014

Website

http://chemistry.fullerton.edu/people/full-time-faculty/231-dr-niroshika-keppetipola