Chen Chen
Graduate student and postdoc positions are available.
Research
Affiliations
Reproductive & Developmental Sciences Programs (RDSP)
Cell and Molecular Biology Program
Genetics and Genome Sciences Program
Laboratory: Germ Cell Biology
My laboratory studies the molecular mechanisms underlying mammalian spermatogenesis and infertility using molecular, cellular, biochemical, mouse genetics and genomics approaches. The lab is broadly interested in genes and pathways influencing germ/stem cell self-renewal, differentiation and fertility with a current focus on the function of Tudor domain proteins and other Piwi-piRNA pathway associated factors in gene silencing, genome stability, epigenetics, stem cell biology and cancer.
Funding
NIH R01 HD084494
Tudor domain proteins in germline genome defense
NIH R01 GM132490
Mitochondria-anchored protein complexes in piRNA biogenesis and function
Selected Publications
Wei C, Yan X, Mann JM, Geng R, Wang Q, Xie H, Demireva EY, Sun L, Ding D, Chen C. PNLDC1 catalysis and postnatal germline function are required for piRNA trimming, LINE1 silencing, and spermatogenesis in mice. PLoS Genet. 2024 Sep 23;20(9):e1011429. doi: 10.1371/journal.pgen.1011429.
Wei C, Jing J, Yan X, Mann JM, Geng R, Xie H, Demireva EY, Hess RA, Ding D, Chen C. MIWI N-terminal RG motif promotes efficient pachytene piRNA production and spermatogenesis independent of LINE1 transposon silencing. PLoS Genet. 2023 Nov 13;19(11):e1011031. doi: 10.1371/journal.pgen.1011031.
Liu J, Hermo L, Ding D, Wei C, Mann JM, Yan X, Melnick AF, Wu Y, Withrow A, Cibelli J, Hess RA, Chen C. SYPL1 defines a vesicular pathway essential for sperm cytoplasmic droplet formation and male fertility. Nat Commun. 2023 Aug 22;14(1):5113. doi: 10.1038/s41467-023-40862-1.
Ding D, Wei C, Dong K, Liu J, Stanton A, Xu C, Min J, Hu J, Chen C. LOTUS domain is a novel class of G-rich and G-quadruplex RNA binding domain. Nucleic Acids Res. 2020 Aug 7:gkaa652. doi: 10.1093/nar/gkaa652.
Sun YH, Zhu J, Xie LH, Li Z, Meduri R, Zhu X, Song C, Chen C, Ricci EP, Weng Z, Li XZ. Ribosomes guide pachytene piRNA formation on long intergenic piRNA precursors. Nat Cell Biol. 2020 Feb 3. doi: 10.1038/s41556-019-0457-4.
Ding D, Liu J, Dong K, Melnick A, Latham KE, Chen C. Mitochondrial membrane-based initial separation of MIWI and MILI functions during pachytene piRNA biogenesis. Nucleic Acids Res. 2018, Dec 22. DOI:10.1093/nar/gky1281.
Ding D, Liu J, Midic U, Wu Y, Dong K, Melnick A, Latham KE, Chen C. TDRD5 binds piRNA precursors and selectively enhances pachytene piRNA processing in mice. Nat Commun. 2018 Jan 9;9(1):127. doi: 10.1038/s41467-017-02622-w.
Zhang H, Liu K, Izumi N, Huang H, Ding D, Ni Z, Sidhu SS, Chen C, Tomari Y, Min J. Structural basis for arginine methylation-independent recognition of PIWIL1 by TDRD2. Proc Natl Acad Sci U S A. 2017 Nov 8. pii: 201711486. doi: 10.1073/pnas.1711486114.
Ding D, Liu J, Dong K, Midic U, Hess RA, Xie H, Demireva EY, Chen C. PNLDC1 is essential for piRNA 3’ end trimming and transposon silencing during spermatogenesis in mice. Nat Commun. 2017 Oct 10;8(1):819. doi: 10.1038/s41467-017-00854-4.
Chen C*, Nott TJ, Jin J, Pawson T*. Deciphering arginine methylation: Tudor tells the tale. Nat Rev Mol Cell Biol. 2011 Sep 14;12(10):629-42. *Corresponding author.
Xu C, Bian C, Yang W, Galka M, Ouyang H, Chen C, Qiu W, Liu H, Jones AE, Mackenzie F, Pan P, Li SS, Wang H, Min J. Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2). Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19266-7.
Liu K*, Chen C*, Guo Y*, Lam R, Bian C, Xu C, Zhao DY, Jin J, MacKenzie F, Pawson T, Min J. Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18398-403. *Equal contribution.
Chen C, Jin J, James DA, Adams-Cioaba MA, Park JG, Guo Y, Tenaglia E, Xu C, Gish G, Min J, Pawson T. Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20336-41.
Jin J, Xie X*, Chen C*, Park JG, Stark C, James DA, Olhovsky M, Linding R, Mao Y, Pawson T. Eukaryotic protein domains as functional units of cellular evolution. Science Signaling. 2009 Nov 24;2(98):ra76. *Equal contribution.
Chen C, Ouyang W, Grigura V, Zhou Q, Lim H, Zhao GQ, Carnes K, Arber S, Kurpios N, Murphy TL, Cheng AM, Hassell JA, Chandrashekar V, Hofmann M, Hess RA, Murphy KM. ERM is required for transcriptional control of the spermatogonial stem cell niche. Nature. 2005 August 18; 436:1030-34.
Teaching
ANS 815 - Advanced Topics in Reproduction and Development (Course director)
ANS 307 - Animal Reproduction
Related Work
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2017 Animal Science Graduate Research Forum
Published on October 23, 2017
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Genetic Advance for Male Birth Control
Published on October 16, 2017