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Heng-Chi Lee

TitleAssociate Professor
InstitutionUniversity of Chicago
DepartmentMolecular Genetics and Cell Biology
AddressChicago IL 60637
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    Small non-coding RNAs play remarkable roles in regulating gene expression by binding to Argonaute family proteins and guiding them to recognize their targets. We are interested in understanding how small RNAs function as a surveillance system that defends the genome against foreign nucleic acids, such as transposons. A conserved subfamily of Argonaute, named PIWI, binds PIWI-interacting RNA (piRNA) and plays critical roles in silencing transposons in various animals. Using C. elegans as a model organism, our recent study suggests PIWI and >25,000 genome-encoded piRNAs survey the whole transcriptome to detect "non-self" nucleic acids. Interestingly, our research demonstrated that piRNAs can establish "non-self memory" that silences its targets over multiple generations! In addition, self-transcripts appear to be protected by another group of small RNAs from piRNA silencing.

    Genetic analyses have laid the groundwork for our knowledge of this defense system, but the molecular mechanisms are still poorly understood. We aim to investigate several fundamental questions including: 1. How do piRNAs recognize their RNA targets/ 2. How are "self" and "non-self" memories established and inherited? 3. How are various small RNAs produced and specifically associated with distinct Argonaute complexes? By applying complementary approaches including genomics, genetics and biochemistry, we aim to identify important principles of small RNA-based genome defense mechanisms that are likely conserved between different animals. Importantly, as PIWI mutants exhibit fertility defects in various animals, we hope our research will provide important insights toward the molecular pathogenesis of infertility.
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    R01GM132457     (LEE, HENG-CHI)May 1, 2019 - Jan 31, 2025
    NIH
    piRNA-mediated genome surveillance of germline transcripts
    Role: Principal Investigator

    R00GM108866     (LEE, HENG-CHI)Sep 1, 2014 - Dec 31, 2018
    NIH
    Mechanism of piRNA-mediated recognition and silencing of foreign genes
    Role: Principal Investigator

    K99GM108866     (LEE, HENG-CHI)Sep 1, 2014 - Jul 31, 2016
    NIH
    Mechanism of piRNA-mediated recognition and silencing of foreign genes
    Role: Principal Investigator

    F32GM099372     (LEE, HENG-CHI)Aug 1, 2011 - Jul 31, 2014
    NIH
    Investigating the Biogenesis and Function of piRNAs in Germline Development
    Role: Principal Investigator

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Zhang D, Gaylord O, Chen W, Lee HC, Brown JS. Sensitized piRNA reporter identifies multiple RNA processing factors involved in piRNA-mediated gene silencing. Genetics. 2023 08 09; 224(4). PMID: 37210214; PMCID: PMC10691750.
      Citations: 2     Fields:    Translation:AnimalsCells
    2. Brown J, Zhang D, Chen W, Lee HC. Sensitized piRNA reporter identifies multiple RNA processing factors involved in piRNA-mediated gene silencing. bioRxiv. 2023 Jan 22. PMID: 36712000; PMCID: PMC9882300.
      Citations:    
    3. Chen W, Brown JS, He T, Wu WS, Tu S, Weng Z, Zhang D, Lee HC. GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance. Nat Commun. 2022 09 09; 13(1):5306. PMID: 36085149; PMCID: PMC9463143.
      Citations: 6     Fields:    Translation:AnimalsCells
    4. Wu WS, Brown JS, Chen PH, Shiue SC, Lee DE, Lee HC. CLASH Analyst: A Web Server to Identify In Vivo RNA-RNA Interactions from CLASH Data. Noncoding RNA. 2022 Jan 12; 8(1). PMID: 35076587; PMCID: PMC8788457.
      Citations: 1     
    5. Lee HH, Wang YN, Yang WH, Xia W, Wei Y, Chan LC, Wang YH, Jiang Z, Xu S, Yao J, Qiu Y, Hsu YH, Hwang WL, Yan M, Cha JH, Hsu JL, Shen J, Ye Y, Wu X, Hou MF, Tseng LM, Wang SC, Pan MR, Yang CH, Wang YL, Yamaguchi H, Pang D, Hortobagyi GN, Yu D, Hung MC. Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation. Nat Commun. 2021 05 13; 12(1):2788. PMID: 33986289; PMCID: PMC8119676.
      Citations: 12     Fields:    Translation:HumansAnimalsCells
    6. Chen W, Hu Y, Lang CF, Brown JS, Schwabach S, Song X, Zhang Y, Munro E, Bennett K, Zhang D, Lee HC. The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle. Genetics. 2020 06; 215(2):421-434. PMID: 32245789; PMCID: PMC7268986.
      Citations: 16     Fields:    Translation:AnimalsCells
    7. Wu WS, Brown JS, Chen TT, Chu YH, Huang WC, Tu S, Lee HC. piRTarBase: a database of piRNA targeting sites and their roles in gene regulation. Nucleic Acids Res. 2019 01 08; 47(D1):D181-D187. PMID: 30357353; PMCID: PMC6323935.
      Citations: 31     Fields:    Translation:Cells
    8. Wu WS, Huang WC, Brown JS, Zhang D, Song X, Chen H, Tu S, Weng Z, Lee HC. pirScan: a webserver to predict piRNA targeting sites and to avoid transgene silencing in C. elegans. Nucleic Acids Res. 2018 07 02; 46(W1):W43-W48. PMID: 29897582; PMCID: PMC6030828.
      Citations: 19     Fields:    Translation:Animals
    9. Zhang D, Tu S, Stubna M, Wu WS, Huang WC, Weng Z, Lee HC. The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes. Science. 2018 02 02; 359(6375):587-592. PMID: 29420292; PMCID: PMC5939965.
      Citations: 105     Fields:    Translation:Animals
    10. Tang W, Tu S, Lee HC, Weng Z, Mello CC. The RNase PARN-1 Trims piRNA 3' Ends to Promote Transcriptome Surveillance in C. elegans. Cell. 2016 Feb 25; 164(5):974-84. PMID: 26919432; PMCID: PMC4785802.
      Citations: 73     Fields:    Translation:AnimalsCells
    11. Gu W, Lee HC, Chaves D, Youngman EM, Pazour GJ, Conte D, Mello CC. CapSeq and CIP-TAP identify Pol II start sites and reveal capped small RNAs as C. elegans piRNA precursors. Cell. 2012 Dec 21; 151(7):1488-500. PMID: 23260138; PMCID: PMC3581324.
      Citations: 124     Fields:    Translation:AnimalsCells
    12. Lee HC, Gu W, Shirayama M, Youngman E, Conte D, Mello CC. C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell. 2012 Jul 06; 150(1):78-87. PMID: 22738724; PMCID: PMC3410639.
      Citations: 202     Fields:    Translation:AnimalsCells
    13. Shirayama M, Seth M, Lee HC, Gu W, Ishidate T, Conte D, Mello CC. piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell. 2012 Jul 06; 150(1):65-77. PMID: 22738726; PMCID: PMC3597741.
      Citations: 310     Fields:    Translation:AnimalsCells
    14. Lee HC, Aalto AP, Yang Q, Chang SS, Huang G, Fisher D, Cha J, Poranen MM, Bamford DH, Liu Y. The DNA/RNA-dependent RNA polymerase QDE-1 generates aberrant RNA and dsRNA for RNAi in a process requiring replication protein A and a DNA helicase. PLoS Biol. 2010 Oct 05; 8(10). PMID: 20957187; PMCID: PMC2950127.
      Citations: 36     Fields:    Translation:HumansAnimalsCells
    15. Lee HC, Li L, Gu W, Xue Z, Crosthwaite SK, Pertsemlidis A, Lewis ZA, Freitag M, Selker EU, Mello CC, Liu Y. Diverse pathways generate microRNA-like RNAs and Dicer-independent small interfering RNAs in fungi. Mol Cell. 2010 Jun 25; 38(6):803-14. PMID: 20417140; PMCID: PMC2902691.
      Citations: 183     Fields:    Translation:Animals
    16. Lee HC, Chang SS, Choudhary S, Aalto AP, Maiti M, Bamford DH, Liu Y. qiRNA is a new type of small interfering RNA induced by DNA damage. Nature. 2009 May 14; 459(7244):274-7. PMID: 19444217; PMCID: PMC2859615.
      Citations: 140     Fields:    Translation:AnimalsCells
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