Education & Training
- B.S.,Departments of Biology and Classical Studies, University of Michigan, Ann Arbor, Michigan, 1991-1995,
- B.S. with Distinction in Biology (High Honors) and Distinction in Latin Language and Literature, University of Michigan, 1995
- Graduate, Department of Genetics, Harvard Medical School, Harvard University, 1996-2003
- Ph.D.,Genetics, Harvard University, 2003
Research Interest Summary
Research Categories
Research Interests
The Kaplan lab studies transcriptional mechanisms of RNA Polymerase II (Pol II), the eukaryotic RNA polymerase responsible for expression of coding genes and many non-coding RNAs. Pol II transcription is also major determinant of eukaryotic chromatin states and therefore impacts gene expression in numerous and unanticipated ways. Our long-term approach to understanding gene expression as impacted by Pol II activity has been to leverage isolation of genetic reagents – Pol II and factor mutants – to advance biochemical, biophysical, and genomic studies on Pol II function. We marry new and emerging technologies to understand Pol II, from systematic genetic interaction studies to deep mutational scanning, to massively parallel promoter assays.
Our selected publications below provide examples of the tools and intellectual infrastructure we are building to reveal Pol II mechanisms. Gene expression aberrancies are a major contributor to many diseases including cancer. Altered cotranscriptional RNA processing is also implicated greatly in a wide range of cancer types and this RNA processing is sensitive to changes in Pol II elongation rate. Understanding how Pol II elongation rate alters transcriptomes in model organisms can reveal paradigms for how altered Pol II function might contribute to disease. To more specifically understand how Pol II defects can cause disease, we are developing new projects in human cell lines to determine mechanisms by which Pol II mutations cause a neurodevelopmental syndrome.
Representative Publications
Zhu, Y., I. O. Vvedenskaya, S. H. Sze, B. E. Nickels and C. D. Kaplan (2024). Quantitative analysis of transcription start site selection reveals control by DNA sequence, RNA polymerase II activity and NTP levels. Nat Struct Mol Biol 31(1): 190-202. https://www.ncbi.nlm.nih.gov/pubmed/38177677, https://www.nature.com/articles/s41594-023-01171-9.pdf
Qiu, C., P. Arora, I. Malik, A. J. Laperuta, E. M. Pavlovic, S. Ugochukwu, M. Naik and C. D. Kaplan (2024). Thiolutin has complex effects in vivo but is a direct inhibitor of RNA polymerase II in vitro. Nucleic Acids Res. https://pubmed.ncbi.nlm.nih.gov/38214235/
Duan, B., C. Qiu, S. H. Sze and C. Kaplan (2023). Widespread epistasis shapes RNA Polymerase II active site function and evolution. bioRxiv. https://www.ncbi.nlm.nih.gov/pubmed/36909581
Dutagaci, B., B. Duan, C. Qiu, C. D. Kaplan and M. Feig (2023). Characterization of RNA polymerase II trigger loop mutations using molecular dynamics simulations and machine learning. PLoS Comput Biol 19(3): e1010999. https://www.ncbi.nlm.nih.gov/pubmed/36947548
Kruglyak, L., A. Beyer, J. S. Bloom, J. Grossbach, T. D. Lieberman, C. P. Mancuso, M. S. Rich, G. Sherlock and C. D. Kaplan (2023). Insufficient evidence for non-neutrality of synonymous mutations. Nature 616(7957): E8-E9. https://www.ncbi.nlm.nih.gov/pubmed/37076734
Zhao, T., I. O. Vvedenskaya, W. K. Lai, S. Basu, B. F. Pugh, B. E. Nickels and C. D. Kaplan (2021). Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae. Elife 10. https://www.ncbi.nlm.nih.gov/pubmed/34652274
Qiu, C., H. Jin, I. Vvedenskaya, J. A. Llenas, T. Zhao, I. Malik, A. M. Visbisky, S. L. Schwartz, P. Cui, P. Cabart, K. H. Han, W. K. M. Lai, R. P. Metz, C. D. Johnson, S. H. Sze, B. F. Pugh, B. E. Nickels and C. D. Kaplan (2020). Universal promoter scanning by Pol II during transcription initiation in Saccharomyces cerevisiae. Genome Biol 21(1): 132. https://www.ncbi.nlm.nih.gov/pubmed/32487207
Malik, I., C. Qiu, T. Snavely and C. D. Kaplan (2017). Wide-ranging and unexpected consequences of altered Pol II catalytic activity in vivo. Nucleic Acids Res 45(8): 4431-4451. https://www.ncbi.nlm.nih.gov/pubmed/28119420
Qiu, C., O. C. Erinne, J. M. Dave, P. Cui, H. Jin, N. Muthukrishnan, L. K. Tang, S. G. Babu, K. C. Lam, P. J. Vandeventer, R. Strohner, J. Van den Brulle, S. H. Sze and C. D. Kaplan (2016). High-Resolution Phenotypic Landscape of the RNA Polymerase II Trigger Loop. PLoS Genet 12(11): e1006321. https://www.ncbi.nlm.nih.gov/pubmed/27898685
Braberg, H., H. Jin, E. A. Moehle, Y. A. Chan, S. Wang, M. Shales, J. J. Benschop, J. H. Morris, C. Qiu, F. Hu, L. K. Tang, J. S. Fraser, F. C. Holstege, P. Hieter, C. Guthrie, C. D. Kaplan and N. J. Krogan (2013). From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II. Cell 154(4): 775-788. http://www.ncbi.nlm.nih.gov/pubmed/23932120