Kevin Van Bortle

Assistant Professor of Cell and Developmental Biology

Research Topics

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

Disease Research Interests

Cancer, Drug Discovery

Education

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

RNA polymerase III transcription, gene regulation, small noncoding RNA

RNA polymerase III (Pol III) transcribes genes encoding tRNA, 5S ribosomal RNA, and other classes of small noncoding RNA involved in translation and other critical processes. Pol III activity is a prerequisite for cell growth and is linked to nutrient availability and extracellular growth cues via oncogenic and tumor-suppressor signaling pathways. Aberrant activation of growth signaling factors can lead to elevated levels of Pol III transcription, a hallmark of cancer.

My lab uses genomic approaches to investigate Pol III transcription dynamics during differentiation and in response to extracellular cues and signaling events. We are particularly interested in understanding the regulatory mechanisms that promote or restrict Pol III activity and which underly Pol III dysregulation in cancer. Our recent work suggests that a specific Pol III subunit, POLR3G, which is highly expressed in proliferative cells and a myriad of cancer contexts, enhances Pol III transcription and drives expression of small NF90-associated (SNAR-A) noncoding RNA. We seek to better understand the mechanism of POLR3G-enhanced transcription, the function of SNAR-A and other Pol III-transcribed small RNA, and the role of POLR3G as a potential disease factor and future therapeutic target.

Awards

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

Representative Publications

Van Bortle, K, Marciano, DP, Liu, Q, Lipchik, AM, Gollapudi, S, Geller, B, Monte, E, Kamakaka, R, Snyder, MP. A cancer-associated RNA polymerase III identity drives robust transcription and expression of SNAR-A noncoding RNA. bioRxiv *preprint*. Cold Spring Harbor Laboratory, p.2021.04.21.440535. doi:10.1101/2021.04.21.440535

Liu, Q, Wu, H, Luo, QJ, Chao, J, Duren, Z, Zhu, C, Zhao, B, Liu, J, Zhao, MT, Narasimha, A, Van Bortle, K, Gruber, JJ, Wei, E, Lipchik, AM, Li, Y, Marciano, DP, Lee, BA, Guo, H, Furihata, T, Tsai, MS, Watson, NK, Tian, L, Steinmetz, LM, Wong, WH, Kay, MA, Wu, JC, Snyder, MP. Tyrosine kinase inhibitors induce cardiac dysfunctions through alterations of GATA4-mediated networks and mitochondrial function during cardiomyocyte differentiation. bioRxiv *preprint*. Cold Spring Harbor Laboratory, p. 2020.05.04.077024. doi: 10.1101/2020.05.04.077024

Liu, Q, Van Bortle, K, Zhang, Y, Zhao, MT, Zhang, JZ, Geller, BS, Gruber, JJ, Chao, J, Wu, JC, Snyder, MP. (2018). Disruption of mesoderm formation during cardiac differentiation due to developmental exposure to 13-cis-retinoic acid. Sci Rep. 8(1):12960

Van Bortle, K, Phanstiel, DH, Snyder, MP. (2017). Topological organization and dynamic regulation of human tRNA genes during macrophage differentiation. Genome Biol. 18(1):180

Phanstiel, DH*, Van Bortle, K*, Spacek, D, Hess, GT, Shamim, MS, Machol, I, Love, MI, Aiden, EL, Bassik, MC, Snyder, MP. (2017). Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development. Mol. Cell. 67(6):1037-1048

Liu, Q, Jiang, C, Xu, J, Zhao, MT, Van Bortle, K, Cheng, X, Wang, G, Chang, HY, Wu, JC, Snyder, MP. (2017). Genome-wide Temporal Profiling of Transcriptome and Open Chromatin of Early Cardiomyocyte Differentiation Derived From hiPSCs and hESCs. Circ. Res. 121(4):376-391

Van Bortle, K, Nichols, M, Ramos, E, Corces, VG. (2015). Integrated tRNA, transcript, and protein profiles in response to steroid hormone signaling. RNA. 21(10)1807-17

Van Bortle, K, Peterson, A, O’Connor, M, Corces, VG. (2015). CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster. Cell Cycle. 14(16):2677-87

Morchoisne-Bolhy, S, Geoffroy, MC, Bouhlel, IB, Alves, A, Audugé, N, Baudin, X, Van Bortle, K, Powers, MA, Doye, V. (2015). Intranuclear Dynamics of the Nup107-160 complex. Mol Biol Cell. 26(12)2343-56

Van Bortle, K, Nichols, M, Li, L, Ong, CT, Takenaka, N, Qin, ZS, Corces, VG. (2014). Insulator function and topological domain border strength scale with architectural protein occupancy. Genome Biol. 15(6):R82

Ong, CT, Van Bortle, K, Ramos, E, Corces, VG. (2013). Poly(ADP-ribosyl)ation regulates insulator function and intrachromosomal interactions in Drosophila. Cell. 155(1):148-159.

Kellner, WA, Van Bortle, K, Li, L, Ramos, E, Takenaka, N, Corces, VG. (2013). Distinct isoforms of the Drosophila Brd4 homologue are present at enhancers, promoters and insulator sites. Nucleic Acids Res. 41(20):9274-9283. Gurudatta BV, Yang J, Van Bortle, K, Donlin-Asp, PG, Corces, V. (2013). Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle. Cell Cycle. 12(10).

Van Bortle, K, Ramos, E, Takenaka, N, Yang, J, Wahi, J, Corces, V. (2012). Drosophila CTCF tandemly aligns with other insulator proteins at the borders of H3K27me3 domains. Genome Res. 22(11)2176-2187.

Kellner, WA, Ramos, E, Van Bortle, K, Takenaka, N, Corces, VG. (2012). Genome-wide phosphoacetylation of histone H3 at Drosophila enhancers and promoters. Genome Res. 22(6):1081-1088.

Wood, A, Van Bortle, K, Ramos, E, Takenaka, N, Rohrbaugh, M, Jones, B, Jones, K, Corces, V. (2011). Regulation of chromatin organization and inducible gene expression by a Drosophila insulator. Mol. Cell. 44(1):29-38

Complete Publications List