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
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.
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. Please submit inquiries to firstname.lastname@example.org.