Trinh Lab Research Opportunities
Bon Trinh, Ph.D.
Assistant Professor of Pathology
Location: MR5 Building, 3226
Thanks to recent advances in the next generation sequencing technologies, many thousands of noncoding RNAs (ncRNA) and regulatory elements called enhancers have been identified throughout the human genome. Recent studies, including our own, pointed to the novel role of ncRNAs in coordinating with proteins to drive gene expression in a cell-type specific manner via chromatin modulation (Trinh et al, Blood J, 2021). Nevertheless, most ncRNAs and enhancers remain to be precisely mapped and functionally defined. The research goals of the Trinh lab are to understand how proteins and ncRNAs coordinate in controlling gene expression via chromatin structure, and to identify novel RNA regulators of cancer-associated genes for therapeutic development. Specifically, we focus on understanding the role of proteins and RNAs via modulation of chromatin architecture in normal and malignant myelopoiesis, and myeloid cell-tumor cell communication in the tumor microenvironment as well as cancer drug resistance. To that end, the lab employs a combination of experimental and computational approaches.
- Overexpression and knock-down of protein-coding and noncoding genes using various approaches (see: What you will learn on this rotation)
- Investigate the effects of gene overexpression and knock down on cell growth and differentiation.
- Generate plasmid constructs for gene overexpression and knock-down.
- Investigate molecular interactions among RNA, DNA, and proteins in normal and cancer cells.
- Examine gene expression profile, molecular interaction profile, or chromatin structure profile using NGS data sets.
What you will learn on this rotation
Depending on student’s background and interests, and priorities of the laboratory, the students will have opportunities to learn various techniques and involve in ongoing research projects
Molecular biology techniques: molecular cloning, real-time RT-PCR, RNA synthesis, western blot, northern blot, RNA pull-down, Immunoprecipitations (RNA-Protein, RNA-chromatin, Protein-Protein, Protein-DNA, Protein-Chromatin), Chromatin 3D structure
Cellular techniques: Depleted or enforced gene expression by CRISPRko, shRNA, siRNA, ASOs, CRISPRa, cDNA, and in vitro transcribed RNAs via viral and non-viral (lipofection and electroporation) delivery methods); Cell growth and differentiation assays, cell staining methods
Animal techniques: Generation and phenotypic analyses of leukemia mouse models
Bioinformatics and statistics: Next generation sequencing analyses of gene expression profile, analyses of global molecular interactions (RNA-Protein, RNA-chromatin, Protein-Protein, Protein-DNA, Protein-Chromatin), and chromatin structure, statistical analyses.
Potential Long-term Projects for thesis
- Protein-ncRNA coordination in myeloid cell development and AML
- Protein-ncRNA coordination in cancer drug response
- Protein-ncRNA coordination in the tumor microenvironment
- Therapeutic strategies “renormalizing” chromatin structure
- Trinh BQ*, Ummarino S, Zhang Y, Ebralidze AK, Bassal MA, Nguyen TM, Heller G, Coffey R, Tenen DE, van der Kouwe E, Fabiani E, Gurnari C, Wu CS, Angarica VE, Yang H, Chen S, Zhang H, Thurm AR, Marchi F, Levantini E, Staber PB, Zhang P, Voso TM, Pandolfi PP, Kobayashi SS, Chai L, Di Ruscio A & Tenen DG*. Myeloid lncRNA LOUP Mediates Opposing Regulatory Effects of RUNX1 and RUNX1-ETO in t(8;21) AML. Blood Journal. 2021. PMID: 33971010 (*corresponding authors).
- van der Kouwe E, Heller G, Czibere A, Agreiter C, Castilla LH, Delwel R, Di Ruscio A, Ebralidze AK, Forte M, Grebien F, Heyes E, Kazianka L, Klinger J, Kornauth C, Le T, Lind K, Barbosa MA, Pemovska T, Pichler A, Pulikkan JA, Schmolke AS, Schweicker C, Sill H, Sperr W, Spittler A, Surapally S, Trinh BQ, Valent P, Vanura K, Welner RS, Zuber J, Tenen DG, Staber BP. Core binding factor leukemias hijack T-cell prone PU.1 antisense promoter. Blood Journal. 2021. PMID: 34010414.
- Umarino S, Hausman C, Gaggi G, Rinaldi L, Bassal MA, Zhang Y, Seelam AJ, Kobayashi IS, Borchiellini M, Ebralidze AK, Ghinassi B, Trinh BQ, Kobayashi SS, Di Ruscio A. NAD modulates DNA methylation and cell differentiation. Cells. 2021. MDPI
- Trinh BQ, Barengo N, Kim SB, Lee JS, Naora H. The homeobox gene DLX4 regulates erythro-megakaryocytic differentiation by stimulating IL-1b and NF-kB signaling. Journal of Cell Science 128(16):3055-67. 2015. PMID: 26208636
- Trinh BQ, Ko SY, Haria D, Barengo N, & Naora H. The homeoprotein DLX4 controls ovarian tumor angiogenesis by regulating expression of inducible nitric oxide synthase. Molecular Cancer. Apr 30;14(1):97. 2015. PMID: 25924901
- Haria D*, Trinh BQ*, Ko SY, Barengo N, Liu JS & Naora H. The homeoprotein DLX4 stimulates NF-κB activation and CD44-mediated tumor-mesothelial cell interactions in ovarian cancer. American Journal of Pathology 185(8):2298-308. 2015. PMID: 26067154 (*equal contribution)
- Trinh BQ, Ko SY, Barengo N, Lin SY, Naora H. Dual functions of the homeoprotein DLX4 in modulating responsiveness of tumor cells to topoisomerase II-targeting drugs. Cancer Research 73:1000-10. 2013. PMID: 23222298
- Trinh BQ, Naora H. Homeobox genes and theirs functional significance in ovarian tumorigenesis, Ovarian Cancer / Book 1, ISBN 978-953-307-812-0, 2012
- Trinh BQ, Barengo N, Naora H. Homeodomain protein DLX4 counteracts key transcriptional control mechanisms of the TGF-b cytostatic program and blocks the anti-proliferative effect of TGF-b. Oncogene 30: 2718-2729. 2011. PMID: 21297662
- Xie X, Hsu JL, Choi MG, Xia W, Yamaguchi H, Chen CT, Trinh BQ, Lu Z, Ueno NT, Wolf JK, Bast RC Jr, Hung MC. A novel hTERT promoter-driven E1A therapeutic for ovarian cancer. Molecular Cancer Therapeutics Aug;8(8):2375-82. 2009. PMID: 19671744