Zhongsheng You

Associate Professor of Cell Biology and Physiology, Associate Professor of Medicine

    • 1926 Citations
    19972020

    Research output per year

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    Personal profile

    Research interests

    The surveillance systems that safeguard the genome and the transcriptome ensure faithful transmission and expression of genetic information and determine the function and the fate of the cell. Defects in these systems are associated with cancer, aging and neurological disorders. Our laboratory is interested in understanding the molecular basis of the DNA and RNA surveillance systems and their relation to human diseases, especially cancer. Our work in DNA surveillance is focused on the cellular response to the most dangerous type of DNA damage, DNA double-strand breaks. This highly sophisticated DNA damage response suppresses cancer formation and is also an important target of cancer therapy. Our work has contributed to the understanding of a number of key biochemical processes such as ATM activation and DNA end resection in the DNA damage response. Currently, we are pursuing the following fundamental questions: 1. How do cells read the DNA damage signal and translate the signal into downstream checkpoint and repair responses? 2. How do cells maintain genome stability during DNA replication and gene expression? In the RNA surveillance area, we focus on the nonsense-mediated mRNA decay (NMD) pathway. NMD selectively eliminates aberrant transcripts harboring premature translation termination codons and also regulates the levels of many physiological mRNAs. NMD is an attractive target of therapeutic intervention for cancer and other genetic diseases (e.g., cystic fibrosis and Duchenne muscular dystrophy). Through a high-throughput drug screen using a novel reporter system, we have recently identified a group of cardiac glycosides such as ouabain and digoxin as potent inhibitors of NMD. Furthermore, we have discovered that intracellular calcium is a key regulator of NMD. Our current work is aimed at elucidating the mechanism and physiological significance of the calcium regulation of NMD. In addition, we are pursuing the potential connections between RNA surveillance and DNA surveillance pathways. We employ a powerful combination of experimental systems and tools, including human cell culture, Xenopus egg extracts, laser microirradiation, genetically encoded reporters and live cell imaging, to dissect the DNA and RNA surveillance systems—with the long-term goal of improving the treatment of cancer and other diseases.

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    Research Output

    • 1926 Citations
    • 29 Article
    • 3 Review article
    • 1 Chapter

    Phospho-Ser784-VCP Is Required for DNA Damage Response and Is Associated with Poor Prognosis of Chemotherapy-Treated Breast Cancer

    Zhu, C., Rogers, A., Asleh, K., Won, J., Gao, D., Leung, S., Li, S., Vij, K. R., Zhu, J., Held, J. M., You, Z., Nielsen, T. O. & Shao, J., Jun 9 2020, In : Cell Reports. 31, 10, 107745.

    Research output: Contribution to journalArticle

    Open Access
  • 1 Scopus citations

    Ca2+-Stimulated AMPK-Dependent Phosphorylation of Exo1 Protects Stressed Replication Forks from Aberrant Resection

    Li, S., Lavagnino, Z., Lemacon, D., Kong, L., Ustione, A., Ng, X., Zhang, Y., Wang, Y., Zheng, B., Piwnica-Worms, H., Vindigni, A., Piston, D. W. & You, Z., Jun 20 2019, In : Molecular cell. 74, 6, p. 1123-1137.e6

    Research output: Contribution to journalArticle

  • 10 Scopus citations

    Repair of protein-linked DNA double strand breaks: Using the adenovirus genome as a model substrate in cell-based assays

    Lamarche, B. J., Orazio, N. I., Goben, B., Meisenhelder, J., You, Z., Weitzman, M. D. & Hunter, T., Feb 2019, In : DNA Repair. 74, p. 80-90 11 p.

    Research output: Contribution to journalArticle

  • 1 Scopus citations

    Compound C inhibits nonsense-mediated RNA decay independently of AMPK

    Cheruiyot, A., Li, S., Nickless, A., Roth, R., Fitzpatrick, J. A. J. & You, Z., Oct 2018, In : PloS one. 13, 10, e0204978.

    Research output: Contribution to journalArticle

    Open Access
  • 1 Scopus citations

    Studying nonsense-mediated mRNA decay in mammalian cells using a multicolored bioluminescence-based reporter system

    Nickless, A. & You, Z., Jan 1 2018, Methods in Molecular Biology. Humana Press Inc., p. 213-224 12 p. (Methods in Molecular Biology; vol. 1720).

    Research output: Chapter in Book/Report/Conference proceedingChapter

  • 1 Scopus citations