Overall, understanding the mechanisms underlying R-loop-mediated genomic instability may provide key insights into (1) unannotated biological pathways; (2) the pathogenesis of many diseases and syndromes including cancer and neurological disorders; and (3) identification of novel targets and innovative strategies to leverage the formation, resolution, and/or processing of R-loops for precision medicine.
Current Research Funding
CTSI Biomedical Research Grant PI: Edward A. Motea 11/19/2018-11/18/2019
Goal: To elucidate the role of PARP1/RPRD1B in co-transcriptional R-loop-induced genomic instability.
Role: Principal Investigator
NIH/NCI, 1 R01 CA201489-02, Role: Co-Investigator (PI: Boothman, DA) 07/01/2016-06/30/2021
This grant focuses on the lab’s discovery that Kub5/Hera (K-H) regulates RNAPII at specific genetic promoters that include CDK1 in a subset of BRCA-proficient cancers. Loss of K-H expression compromises homologous recombination (HR) and hypersensitizes cells to PARP inhibitors. Aim 1 focuses on determining the structure/function of K-H regulation of the CTD domain of RNPII binding to specific promoter regions of CDK1. Aim 2 studies examine the therapeutic index of K-H-deficient breast cancers that are, in turn, hypersensitive to PARP inhibitors. Overlap: None.
Motea, E. A., Huang X, Singh N, Kilgore J, Williams N, Xie XJ, Gerber D, Beg MS, et al. (2019) NQO1-dependent, tumor-selective radiosensitization of non-small cell lung cancers. Clinical Cancer Research, 25 (8), 2601-2609. PMID: 30617135.
Motea E. A.#, Fattah, F. J., Xiao, L., Girard, L., Rommel, A., Morales, J. C., Patidar, P. L., Zhou, Y., Porter, A. C., Xie, Y., Minna, J. D., Boothman, D. A.# (2018) Kub5-Hera/RPRD1B deficiency promotes “BRCAness” and vulnerability to PARP inhibition in BRCA-proficient Breast Cancers, Clinical Cancer Research, 24 (24), 6459-6470. PMCID: PMC6295248, #co-corresponding authors
Choi JS, Kim S, Motea E, Berdis A. Inhibiting translesion DNA synthesis as an approach to combat drug resistance to DNA damaging agents. Oncotarget. 2017 Jun 20;8(25):40804-40816. doi: 10.18632/oncotarget.17254. PubMed PMID: 28489578; PubMed Central PMCID: PMC5522278.
Yan Y, Zhou K, Xiong H, Miller JB, Motea EA, Boothman DA, Liu L, Siegwart DJ. Aerosol delivery of stabilized polyester-siRNA nanoparticles to silence gene expression in orthotopic lung tumors. Biomaterials. 2017 Feb;118:84-93. doi: 10.1016/j.biomaterials.2016.12.001. Epub 2016 Dec 2. PubMed PMID: 27974266.
Huang X, Motea EA, Moore ZR, Yao J, Dong Y, Chakrabarti G, Kilgore JA, Silvers MA, Patidar PL, Cholka A, et al. Leveraging an NQO1 Bioactivatable Drug for Tumor-Selective Use of Poly(ADP-ribose) Polymerase Inhibitors. Cancer Cell. 2016 Dec 12;30(6):940-952. doi: 10.1016/j.ccell.2016.11.006. PubMed PMID: 27960087; PubMed Central PMCID: PMC5161231.
Morales JC, Richard P, Patidar PL, Motea EA, Dang TT, Manley JL, Boothman DA. XRN2 Links Transcription Termination to DNA Damage and Replication Stress. PLoS Genet. 2016 Jul 20;12(7):e1006107. doi: 10.1371/journal.pgen.1006107. eCollection 2016 Jul. PubMed PMID: 27437695; PubMed Central PMCID: PMC4954731.
Patidar PL, Motea EA, Fattah FJ, Zhou Y, Morales JC, Xie Y, Garner HR, Boothman DA. The Kub5-Hera/RPRD1B interactome: a novel role in preserving genetic stability by regulating DNA mismatch repair. Nucleic Acids Res. 2016 Feb 29;44(4):1718-31. doi: 10.1093/nar/gkv1492. Epub 2016 Jan 26. PubMed PMID: 26819409; PubMed Central PMCID: PMC4770225.
The Motea lab welcomes creative collaborations. There are available openings for bright and highly motivated individuals for graduate and postdoctoral positions in the lab. Interested individuals can submit inquiries by email to firstname.lastname@example.org.