Assistant Professor of Cell & Developmental Biology

Research Interests

Research Topics

Chromatin Structure, Computational Biology, Genome Organization, Genomics, Regulation of Gene Expression, RNA Biology

Disease Research Interests

Cancer, Drug Discovery

Research Description

RNA polymerase III transcription regulation and small noncoding (nc)RNA biology

Our lab is primarily focused on addressing fundamental questions about RNA polymerase III (Pol III) transcription: which genes it transcribes, how its activity is regulated across cell types, and how its RNA products influence cell function. Despite Pol III’s essential role in producing small noncoding RNAs such as tRNAs and 5S rRNA, it remains surprisingly understudied, partly due to technical challenges related to its repetitive gene targets and short, chemically modified RNAs. Yet, Pol III overactivity is a recurring feature in cancer and other disease contexts, highlighting the importance of understanding its regulation. We are developing tailored genomic and biochemical approaches to overcome these barriers and build a comprehensive, functional view of Pol III transcription across diverse biological settings.

Our recent work has revealed unexpected Pol III activity at previously unannotated noncoding RNA genes and uncovered novel interactions between Pol III and Pol II transcriptional programs. We have also identified Pol III-derived small RNAs that influence RNA processing and splicing, pointing to roles that extend beyond classical models of Pol III function. These findings continue to challenge the traditional view of Pol III as a static “housekeeping” enzyme and instead position it as a dynamic regulator that is integrated into broader gene expression networks in a cell type- and context-specific manner.

Looking ahead, our research is aimed at defining how Pol III transcription is shaped during development, differentiation, and disease. We are particularly interested in how chromatin context and regulatory proteins modulate Pol III activity, and how misregulation of this system contributes to pathological states. By combining genome-scale profiling, functional genomics, and mechanistic studies, we aim to expand the conceptual framework for Pol III biology and uncover new principles of RNA-based regulation in human cells.

Education

B.S. 2009 University of Rochester
Ph.D. 2014 Emory University
Postdoc. 2015-2021 Stanford University School of Medicine

Awards and Honors

2019-2024 NIH Pathway to Independence Award (K99/R00)
2015-2018 Ruth L. Kirschstein National Research Service Award (NRSA F32)

Additional Campus Affiliations

Recent Publications

Rajendra, K. C., Cheng, R., Zhou, S., Lizarazo, S., Smith, D. J., & Van Bortle, K. (2024). Evidence of RNA polymerase III recruitment and transcription at protein-coding gene promoters. Molecular cell, 84(21), 4111-4124.e5. https://doi.org/10.1016/j.molcel.2024.09.019

Singh, D. K., Cong, Z., Song, Y. J., Liu, M., Chaudhary, R., Liu, D., Wang, Y., Prasanth, R., K C, R., Lizarazo, S., Akhnoukh, M., Gholamalamdari, O., Moitra, A., Jenkins, L. M., Bhargava, R., Nelson, E. R., Van Bortle, K., Prasanth, S. G., & Prasanth, K. V. (2024). MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of Nuclear Rho-GEF. Molecular and cellular biology, 44(9), 372-390. https://doi.org/10.1080/10985549.2024.2383773

Zhou, S., Lizarazo, S., Mouli, L., Chorghade, S., Cheng, R., Rajendra, K. C., Kalsotra, A., & Van Bortle, K. (2024). Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations. (bioRxiv : the preprint server for biology). https://doi.org/10.1101/2024.07.02.601767

Cheng, R., Zhou, S., K C, R., Lizarazo, S., Mouli, L., Jayanth, A., Liu, Q., & Van Bortle, K. (2023). A Combinatorial Regulatory Platform Determines Expression of RNA Polymerase III Subunit RPC7α (POLR3G) in Cancer. Cancers, 15(20), Article 4995. https://doi.org/10.3390/cancers15204995

Cheng, R., & Van Bortle, K. (2023). RNA polymerase III transcription and cancer: A tale of two RPC7 subunits. Frontiers in Molecular Biosciences, 9, Article 1073795. https://doi.org/10.3389/fmolb.2022.1073795

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