My research interests focused on deciphering the molecular mechanism and signaling in DNA & RNA damage responses. My goal is to apply modern technologies (ex: CRISPR-i screens), integrate cellular and biochemical methods to define the regulatory protein landscape within the DNA / RNA repair signaling and to identify diagnostic and therapeutic targets for cancer treatment.
RNA-Binding Proteins in DNA Repair and PARP Inhibitor Resistance
Poly(ADP-ribose) polymerase inhibitors have become a paradigm for targeted cancer therapy in treating ovarian & breast cancer patients carrying BRCA1/2 mutations. Despite the success of PARP inhibitors in cancer treatment, various resistance mechanisms develop to limit their clinical efficacy. Our lab focused on studying the emerging roles of RNA-binding proteins (RBPs) in DNA repair and sensitivity/resistance to PARP inhibitor.
Poly(ADP-ribose) in Regulating R-loop and Metabolic Enzymes
Poly(ADP-ribose) polymerase-1 (PARP-1) is activated by damaged DNA and synthesizes poly(ADP-ribose), which acts as a scaffold to recruit DNA repair proteins to the site of damage. In addition to the classical role of poly(ADP-ribose) in DNA repair, we are also exploring its involvement in modulating DNA/RNA hybrid (R-loop) formation, as well as the previously unexplored effects of poly(ADP-ribose) on the regulation of metabolic enzymes.
RNA Damage Responses
5-FU’s utility in cancer treatment has long been attributed to inducing dNTP imbalance and DNA damage in cancer cells. Recently, we demonstrate that 5-FU’s efficacy results instead from RNA damage during ribosome biogenesis. We are currently investigating the molecular quality control mechanism by which 5-FU-containing RNAs are sensed and elucidating the signaling pathways linking damaged RNA to cell death.
2018 Ph.D. in Graduate Institute of Cellular and Molecular Biology, University of Texas at Austin
2008 M.S. in Graduate Institute of Microbiology and immunology, National Taiwan University
2006 B.S. in Department of Biological Sciences, National Sun Yat-Sen University
2025 – present, Assistant Professor, Institute of Molecular Medicine, National Taiwan University
2019 – 2024, Postdoctoral Research Scientist, The Koch Institute at MIT
2021 – 2024, Associate Faculty Member, Faculty Opinions (F1000)
Awards and Fellowships
2025 - Talent Recruitment Research Grant, National Taiwan University
2023 - 2030 Cross-Generation Emerging Young Scholar, National Science and Technology Council
2022 - Convergence Scholar Fellowship, Center for Precision Cancer Medicine, Koch Institute, MIT
2021 - Ludwig Center at MIT Postdoctoral Fellow & Fellowship, MIT
- Chen J-K*, Merrick K*, Kong YW, Izrael-Tomasevic A, Eng G, Handly E, Patterson J, Cannell I, Suarez-Lopez L, Hosios A, Dinh A, Kirkpatrick D, Yu K, Rose C, Hwangbo H, Palmer A, Heiden MV, Yilmaz Ö, and Yaffe MB. “An RNA Damage Response Network Mediates the Lethality of 5-FU in Colorectal Cancer.” Cell Rep Med, 2024. (MIT news) (Drug Discovery News).
- Lin W-L*, Chen J-K*, Wen X, He W, Zarceno G, Paull T, Liu H-w. “DDX18 prevents R-loop induced DNA damage and genome instability via PARP-1.” Cell Rep, 2022.
- Sriram G*, Milling L*, Chen J-K, Abrahamd W, Handly E, Irvine D, Yaffe MB. “The Injury Response to DNA Damage Promotes Anti-Tumor Immunity”, Sci Sig, 2021.
- Chen J-K and Yaffe MB. “Atlas Drugged.” (invited preview) Cell, 2019.
- Chen J-K, Lin W-L, Chen Z, Liu H-w. “PARP-1-dependent recruitment of cold-inducible RNA-binding protein promotes double-strand break repair and genome stability.” Proc Natl Acad Sci USA, 2018.
- Lin C-H, Chen J-K, Ko T-M, Wei C-Y, Wu J-Y, Chung W-H, Chen S-Y, Liao Y-D, Hung S-I, Chen YT. “Immunologic basis for allopurinol-induced severe cutaneous adverse reactions: HLA-B*58:01-restricted activation of drug-specific T cells and molecular interaction.” J Allergy Clin Immunol, 2015.
- Kim J, Park RY, Chen J-K, Kim J, Jeong S, Ohn T. “Splicing factor SRSF3 represses the translation of programmed cell death 4 mRNA by associating with the 5′-UTR region.” Cell Death Differ, 2014.
- Ko T-M, Chung W-H, Wei C-Y, Shih H-Y, Chen J-K, Lin C-H, Chen Y-T, Hung S-I. “Shared and restricted T-cell receptor usage is crucial for carbamazepine-induced Stevens–Johnson syndrome.” J Allergy Clin Immunol, 2011.
