@article{holden_park_price_floyd_oldham_2022, title={Evaluation of a method to measure fluorescent cell burden in complex culture systems}, volume={8}, url={http://dx.doi.org/10.1088/2057-1976/ac6701}, DOI={10.1088/2057-1976/ac6701}, abstractNote={Abstract}, number={3}, journal={Biomedical Physics & Engineering Express}, publisher={IOP Publishing}, author={Holden, R and Park, J and Price, A and Floyd, S and Oldham, M}, year={2022}, month={Apr}, pages={037003} }
 @article{edwards_maganti_tanksley_luo_park_balkanska-sinclair_ling_floyd_2020, title={BRD4 Prevents R-Loop Formation and Transcription-Replication Conflicts by Ensuring Efficient Transcription Elongation}, volume={32}, url={http://dx.doi.org/10.1016/j.celrep.2020.108166}, DOI={10.1016/j.celrep.2020.108166}, abstractNote={<h2>Summary</h2> Effective spatio-temporal control of transcription and replication during S-phase is paramount to maintaining genomic integrity and cell survival. Dysregulation of these systems can lead to conflicts between the transcription and replication machinery, causing DNA damage and cell death. BRD4 allows efficient transcriptional elongation by stimulating phosphorylation of RNA polymerase II (RNAPII). We report that bromodomain and extra-terminal domain (BET) protein loss of function (LOF) causes RNAPII pausing on the chromatin and DNA damage affecting cells in S-phase. This persistent RNAPII-dependent pausing leads to an accumulation of RNA:DNA hybrids (R-loops) at sites of BRD4 occupancy, leading to transcription-replication conflicts (TRCs), DNA damage, and cell death. Finally, our data show that the BRD4 C-terminal domain, which interacts with P-TEFb, is required to prevent R-loop formation and DNA damage caused by BET protein LOF.}, number={12}, journal={Cell Reports}, publisher={Elsevier BV}, author={Edwards, Drake S. and Maganti, Rohin and Tanksley, Jarred P. and Luo, Jie and Park, James J.H. and Balkanska-Sinclair, Elena and Ling, Jinjie and Floyd, Scott R.}, year={2020}, month={Sep}, pages={108166} }
 @article{tay_park_price_engelward_floyd_2020, title={HTS-Compatible CometChip Enables Genetic Screening for Modulators of Apoptosis and DNA Double-Strand Break Repair}, volume={5}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85085376126&partnerID=MN8TOARS}, DOI={10.1177/2472555220918367}, abstractNote={Dysfunction of apoptosis and DNA damage response pathways often drive cancer, and so a better understanding of these pathways can contribute to new cancer therapeutic strategies. Diverse discovery approaches have identified many apoptosis regulators, DNA damage response, and DNA damage repair proteins; however, many of these approaches rely on indirect detection of DNA damage. Here, we describe a novel discovery platform based on the comet assay that leverages previous technical advances in assay precision by incorporating high-throughput robotics. The high-throughput screening (HTS) CometChip is the first high-throughput-compatible assay that can directly detect physical damage in DNA. We focused on DNA double-strand breaks (DSBs) and utilized our HTS CometChip technology to perform a first-of-its-kind screen using an shRNA library targeting 2564 cancer-relevant genes. Conditions of the assay enable detection of DNA fragmentation from both exogenous (ionizing radiation) and endogenous (apoptosis) sources. Using this approach, we identified LATS2 as a novel DNA repair factor as well as a modulator of apoptosis. We conclude that the HTS CometChip is an effective assay for HTS to identify modulators of physical DNA damage and repair.}, number={8}, journal={SLAS DISCOVERY: Advancing the Science of Drug Discovery}, publisher={SAGE Publications}, author={Tay, Ian J. and Park, James J. H. and Price, Anna L. and Engelward, Bevin P. and Floyd, Scott R.}, year={2020}, month={May}, pages={247255522091836} }
 @article{nehama_di ianni_musio_du_patané_pollo_finocchiaro_park_dunn_edwards_et al._2019, title={B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres.}, volume={47}, url={http://europepmc.org/articles/PMC6796553}, DOI={10.1016/j.ebiom.2019.08.030}, abstractNote={BackgroundThe dismal survival of glioblastoma (GBM) patients urgently calls for the development of new treatments. Chimeric antigen receptor T (CAR-T) cells are an attractive strategy, but preclinical and clinical studies in GBM have shown that heterogeneous expression of the antigens targeted so far causes tumor escape, highlighting the need for the identification of new targets. We explored if B7-H3 is a valuable target for CAR-T cells in GBM.MethodsWe compared mRNA expression of antigens in GBM using TCGA data, and validated B7-H3 expression by immunohistochemistry. We then tested the antitumor activity of B7-H3-redirected CAR-T cells against GBM cell lines and patient-derived GBM neurospheres in vitro and in xenograft murine models.FindingsB7-H3 mRNA and protein are overexpressed in GBM relative to normal brain in all GBM subtypes. Of the 46 specimens analyzed by immunohistochemistry, 76% showed high B7-H3 expression, 22% had detectable, but low B7-H3 expression and 2% were negative, as was normal brain. All 20 patient-derived neurospheres showed ubiquitous B7-H3 expression. B7-H3-redirected CAR-T cells effectively targeted GBM cell lines and neurospheres in vitro and in vivo. No significant differences were found between CD28 and 4-1BB co-stimulation, although CD28-co-stimulated CAR-T cells released more inflammatory cytokines.InterpretationWe demonstrated that B7-H3 is highly expressed in GBM specimens and neurospheres that contain putative cancer stem cells, and that B7-H3-redirected CAR-T cells can effectively control tumor growth. Therefore, B7-H3 represents a promising target in GBM.FundAlex's Lemonade Stand Foundation; Il Fondo di Gio Onlus; National Cancer Institute; Burroughs Wellcome Fund.}, journal={EBioMedicine}, author={Nehama, D. and Di Ianni, N. and Musio, S. and Du, H. and Patané, M. and Pollo, B. and Finocchiaro, G. and Park, J.J.H. and Dunn, D.E. and Edwards, D.S. and et al.}, year={2019}, month={Aug}, pages={33–43} }
 @article{edwards_maganti_tanksley_luo_park_balkanska-sinclair_ling_floyd_2019, title={BRD4 Prevents R-Loop Formation and Transcription-Replication Conflicts by Ensuring Efficient Transcription Elongation}, volume={11}, url={https://doi.org/10.1101/854737}, DOI={10.1101/854737}, abstractNote={ABSTRACT}, publisher={Cold Spring Harbor Laboratory}, author={Edwards, Drake and Maganti, Rohin and Tanksley, Jarred P. and Luo, Jie and Park, James J.H. and Balkanska-Sinclair, Elena and Ling, Jinjie and Floyd, Scott R.}, year={2019}, month={Nov} }