Welcome to the Van Bortle Lab
Our group combines biochemical, molecular and genomic approaches to investigate RNA polymerase III (Pol III) transcription dynamics and mechanisms and pathways that regulate Pol III. We are probing the full extent of Pol III transcription, its dynamic, context-specific activities during development, and the regulatory factors and molecular events that modulate Pol III activity. We are also pursuing the functional activities and consequences of specific, cancer-associated small ncRNA expressed by Pol III with the overarching goal of understanding how Pol III contributes to cancer growth and metastasis.
Our genes are expressed by three DNA-dependent RNA polymerase machineries, Pol I, Pol II, and Pol III. RNA polymerase III (Pol III) is unique in that it exclusively transcribes genes encoding small noncoding RNA (ncRNA), many of which are critical for cell growth and proliferation. Upregulation of Pol III activity and specific small ncRNA are hallmarks of cancer. Currently, a mechanistic understanding of the events that give rise to Pol III overactivity and the downstream functions of multiple cancer-associated small RNA species remains lacking.
The Pol III apparatus itself is unique in multiple respects, including the fact that Pol III switches its "identity" by replacing a single subunit during mammalian development. We have recently found that one form of Pol III, which re-emerges in many cancer types and is associated with poor survival outcomes, promotes the expression of specific small ncRNA implicated in cancer growth and metastasis. We are investigating the mechanisms underlying Pol III identity-driven transcription potential, as well as the downstream function(s) of Pol III-derived small ncRNA with the goal of deconstructing the relationship between Pol III overactivity, cancer growth, and health outcomes.
11.11.23 | Jenny, Rajendra, Sihang and Simon presented their work at the Cell and Developmental Biology (CDB) Department Retreat at Allerton
11.02.23 | Anshita and Leela presented their undergraduate research at the MCB Undergraduate Research Symposium! Congratulations Leela on receiving the School of MCB Director's Award for Exceptional Research Presentation!
10.15.23 | Our study of predicted regulatory features underlying POLR3G expression is published in a special issue on RNA polymerase I and III in Cancer. Congratulations first authors Jenny and Sihang and the rest of the team!
05.15.23 | Welcome undergraduate students David Condroski (Computer Science) and Jamie Im (Chemistry)!
05.09.23 | Rajendra passes Biophysics qualifying exam
05.01.23 | Anshita and Leela receive MCB Summer Undergraduate Research Fellowships (SURFs)
04.10.23 | Sihang passes CDB preliminary exam
04.04.23 | Jenny passes CDB preliminary exam
02.08.23 | Sihang's review on the Pol III transcriptome is published in WIREs RNA!
01.12.23 | Jenny's mini-review on Pol III RPC7 subunits (POLR3G and POLR3GL) is published in Frontiers Molecular Biosciences!
10.22.22 | Sihang and Jenny presented their work at the CDB
Cell and Developmental Biology Retreat, congratulations Sihang on winning a 3MT award!
09.01.22 | Welcome MCB undergraduate students Anshita Jayanth and Leela Mouli and Graduate Student Simón Lizarazo from Molecular and Integrative Physiology (MIP)
01.12.22 | Welcome graduate student Rajendra K C from the Center for Biophysics & Quantitative Biology (CBQB)
11.01.21 | Hello World from the Van Bortle Lab. Welcome graduate students Sihang Zhou and Ruiying (Jenny) Cheng from Molecular & Cell Biology (MCB)
Cheng R*, Zhou S*, K C R‡ , Lizarazo S,‡ Mouli L, Jayanth A, Liu Q, Van Bortle K#.
Cancers. 2023 15(20) 4995. doi: 10.3390/cancers15204995
Zhou S, Van Bortle K#.
Wiley Interdiscip Rev RNA. 2023 Feb 8:e1782. doi: 10.1002/wrna.1782
Cheng R, Van Bortle K#.
Front Mol Biosci. 2023 Jan 12;9:1073795. doi: 10.3389/fmolb.2022.1073795.
Van Bortle K, Marciano DP, Liu Q, Chou T, Lipchik AM, Gollapudi S, Geller BS, Monte E, Kamakaka RT, Snyder MP.
Nat Commun. 2022 May 30;13(1):3007. doi: 10.1038/s41467-022-30323-6
Van Bortle K, Phanstiel DH, Snyder MP.
Genome Biol. 2017 Sep 20;18(1):180. doi: 10.1186/s13059-017-1310-3
Phanstiel DH*, Van Bortle K*, Spacek D, Hess GT, Shamim MS, Machol I, Love MI, Aiden EL, Bassik MC, Snyder MP.
Mol Cell. 2017 Sep 21;67(6):1037-1048.e6. doi: 10.1016/j.molcel.2017.08.006
Van Bortle K, Nichols MH, Ramos E, Corces VG.
RNA. 2015 Oct;21(10):1807-17. doi: 10.1261/rna.052126.115
Van Bortle K, Nichols MH, Li L, Ong CT, Takenaka N, Qin ZS, Corces VG.
Genome Biol. 2014 Jun 30;15(6):R82. doi: 10.1186/gb-2014-15-5-r82
Simón Lizarazo and Rajendra K C
R package for quantifying and visualizing feature dominance in datasets. dominatR makes use of Shannon's entropy to identify features that are dominated within a particular category or condition. Includes built-in functions for data normalization, categorical entropy calculation, and feature dominance visualization.
Integration of disparate coding and noncoding annotations to define promoter regions for holistic studies of RNA polymerase I, II, and III. Briefly, related transcript start sites (TSS) are clustered and a promoter window is uniformly defined as 200 bp (position -150 to position +50 centered on a median cluster TSS). Promoters are defined individually for RNA subtypes and compiled into a master promoter file.
Graduate-level course that emphasizes core concepts and methods in functional genomics. Students are introduced to Linux / HPC environments, programming in R, and statistical methods . Students are tasked with retrieving, processing, and integrating multiple genomic modalities (shRNA RNA-seq, ChIP-seq, eCLIP) to address questions related to the regulation and function of a specific DNA-RNA-binding protein, with the overall goal of gaining proficiency in computational analysis