Fellowship Princeton University, Postdoctoral Fellow - Molecular Biology University of Pittsburgh, PhD - Molecular Biology

Our laboratory mainly focuses on studying the p53 pathway in tumor cells. Recent work involve the p53 regulator MDMX. We are investigating the regulation of MDMX by ubiquitination and phosphorylation, the roles of MDMX in regulating p53 response to DNA damage and ribosomal stress, and the role of MDMX in tumor formation. We are also trying to develop inhibitors against MDM2 and MDMX as therapeutic agents. A second area of research addresses the role of SirT1 in stress response in tumor cells, regulation of SirT1 expression by E2F1, and the role of SirT1 phosphorylation.

Huang Q, Chen L, Schonbrunn E, Chen J. MDMX inhibits casein kinase 1α activity and stimulates Wnt signaling. Embo J. 2020 Jun.39(14):e104410. Pubmedid: 32511789. Pmcid: PMC7361285. Li Q, Karim RM, Cheng M, Das M, Chen L, Zhang C, Lawrence HR, Daughdrill GW, Schonbrunn E, Ji H, Chen J. Inhibition of p53 DNA binding by a small molecule protects mice from radiation toxicity. Oncogene. 2020 Jun.39(29):5187-5200. Pubmedid: 32555331. Pmcid: PMC7398576. Liu X, Huang Q, Chen L, Zhang H, Schonbrunn E, Chen J. Tumor-derived CK1α mutations enhance MDMX inhibition of p53. Oncogene. 2020 Jan.39(1):176-186. Pubmedid: 31462704. Sang P, Shi Y, Lu J, Chen L, Yang L, Borcherds W, Abdulkadir S, Li Q, Daughdrill GW, Chen J, Cai J. α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53-MDM2/MDMX Protein-Protein Interactions. J Med Chem. 2020 Feb.63(3):975-986. Pubmedid: 31971801. Pmcid: PMC7025332. Sang P, Shi Y, Higbee P, Wang M, Abdulkadir S, Lu J, Daughdrill GW, Chen J, Cai J. Rational Design and Synthesis of Right-Handed d-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein-Protein Interactions. J Org Chem. 2020 Aug.85(16):10552-10560. Pubmedid: 32700908. Sang P, Shi Y, Lu J, Chen L, Yang L, Borcherds W, Abdulkadir S, Li Q, Daughdrill G, Chen J, Cai J. Correction to α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53-MDM2/MDMX Protein-Protein Interactions. J Med Chem. 2020 Aug.63(17):10087. Pubmedid: 32822169. Yang L, Song T, Cheng Q, Chen L, Chen J. Mutant p53 Sequestration of the MDM2 Acidic Domain Inhibits E3 Ligase Activity. Mol Cell Biol. 2019 Feb.39(4). Pubmedid: 30455251. Pmcid: PMC6362316. He F, Borcherds W, Song T, Wei X, Das M, Chen L, Daughdrill GW, Chen J. Interaction between p53 N terminus and core domain regulates specific and nonspecific DNA binding. Proc Natl Acad Sci U S A. 2019 Apr.116(18):8859-8868. Pubmedid: 30988205. Pmcid: PMC6500136. Huang Q, Chen L, Yang L, Xie X, Gan L, Cleveland JL, Chen J. MDMX acidic domain inhibits p53 DNA binding in vivo and regulates tumorigenesis. Proc Natl Acad Sci U S A. 2018 Apr.115(15):E3368-E3377. Pubmedid: 29581299. Pmcid: PMC5899450. Borcherds W, Becker A, Chen L, Chen J, Chemes LB, Daughdrill GW. Optimal Affinity Enhancement by a Conserved Flexible Linker Controls p53 Mimicry in MdmX. Biophys J. 2017 May.112(10):2038-2042. Pubmedid: 28487147. Pmcid: PMC5443996. Yang L, Fang J, Chen J. Tumor cell senescence response produces aggressive variants. Cell Death Discov. 2017 Aug.3:17049. Pubmedid: 28845296. Pmcid: PMC5563524. Chen J. The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression. Cold Spring Harb Perspect Med. 2016 Mar.6(3):a026104. Pubmedid: 26931810. Pmcid: PMC4772082. Chen J. Intra molecular interactions in the regulation of p53 pathway. Transl Cancer Res. 2016 Dec.5(6):639-649. Pubmedid: 30613472. Pmcid: PMC6319914. Sun L, Kokura K, Izumi V, Koomen JM, Seto E, Chen J, Fang J. MPP8 and SIRT1 crosstalk in E-cadherin gene silencing and epithelial-mesenchymal transition. EMBO Rep. 2015 Jun.16(6):689-699. Pubmedid: 25870236. Pmcid: PMC4467853. Yang L, Song T, Chen L, Soliman H, Chen J. Nucleolar repression facilitates initiation and maintenance of senescence. Cell Cycle. 2015 Dec.14(22):3613-3623. Pubmedid: 26505814. Pmcid: PMC4825723. Peng L, Yuan Z, Li Y, Ling H, Izumi V, Fang B, Fukasawa K, Koomen J, Chen J, Seto E. Ubiquitinated sirtuin 1 (SIRT1) function is modulated during DNA damage-induced cell death and survival. J Biol Chem. 2015 Apr.290(14):8904-8912. Pubmedid: 25670865. Pmcid: PMC4423681. Chen L, Borcherds W, Wu S, Becker A, Schonbrunn E, Daughdrill GW, Chen J. Autoinhibition of MDMX by intramolecular p53 mimicry. Proc Natl Acad Sci U S A. 2015 Apr.112(15):4624-4629. Pubmedid: 25825738. Pmcid: PMC4403185. Zhang M, Xiang S, Joo HY, Wang L, Williams KA, Liu W, Hu C, Tong D, Haakenson J, Wang C, Zhang S, Pavlovicz RE, Jones A, Schmidt KH, Tang J, Dong H, Shan B, Fang B, Radhakrishnan R, Glazer PM, Matthias P, Koomen J, Seto E, Bepler G, Nicosia SV, Chen J, Li C, Gu L, Li GM, Bai W, Wang H, Zhang X. HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSα. Mol Cell. 2014 Jul.55(1):31-46. Pubmedid: 24882211. Pmcid: PMC4188514. Zheng H, Chen L, Pledger WJ, Fang J, Chen J. p53 promotes repair of heterochromatin DNA by regulating JMJD2b and SUV39H1 expression. Oncogene. 2014 Feb.33(6):734-744. Pubmedid: 23376847. Pmcid: PMC3912226. Schneeberger VE, Luetteke N, Ren Y, Berns H, Chen L, Foroutan P, Martinez GV, Haura EB, Chen J, Coppola D, Wu J. SHP2E76K mutant promotes lung tumorigenesis in transgenic mice. Carcinogenesis. 2014 Aug.35(8):1717-1725. Pubmedid: 24480804. Pmcid: PMC4123642. Cheng Q, Song T, Chen L, Chen J. Autoactivation of the MDM2 E3 ligase by intramolecular interaction. Mol Cell Biol. 2014 Aug.34(15):2800-2810. Pubmedid: 24842904. Pmcid: PMC4135571. Yang L, Chen J. SirT1 and rRNA in the nucleolus: regulating the regulator. Oncoscience. 2014.1(2):111-112. Pubmedid: 25594003. Pmcid: PMC4278288. Yang L, Song T, Chen L, Kabra N, Zheng H, Koomen J, Seto E, Chen J. Regulation of SirT1-nucleomethylin binding by rRNA coordinates ribosome biogenesis with nutrient availability. Mol Cell Biol. 2013 Oct.33(19):3835-3848. Pubmedid: 23897426. Pmcid: PMC3811878. Gray JE, Altiok S, Alexandrow MG, Walsh FW, Chen J, Schell MJ, Tai DF, Bepler G. Phase 2 randomized study of enzastaurin (LY317615) for lung cancer prevention in former smokers. Cancer. 2013 Mar.119(5):1023-1032. Pubmedid: 23065656. Pmcid: PMC3578040. Song T, Yang L, Kabra N, Chen L, Koomen J, Haura EB, Chen J. The NAD+ synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription. J Biol Chem. 2013 Jul.288(29):20908-20917. Pubmedid: 23737528. Pmcid: PMC3774361. Zheng H, Yang L, Peng L, Izumi V, Koomen J, Seto E, Chen J. hMOF acetylation of DBC1/CCAR2 prevents binding and inhibition of SirT1. Mol Cell Biol. 2013 Dec.33(24):4960-4970. Pubmedid: 24126058. Pmcid: PMC3889553. Hodul PJ, Dong Y, Husain K, Pimiento JM, Chen J, Zhang A, Francois R, Pledger WJ, Coppola D, Sebti SM, Chen DT, Malafa MP. Vitamin E δ-tocotrienol induces p27(Kip1)-dependent cell-cycle arrest in pancreatic cancer cells via an E2F-1-dependent mechanism. PLoS One. 2013 Aug.8(2):e52526. Pubmedid: 23393547. Pmcid: PMC3564846. Tang J, Agrawal T, Cheng Q, Qu L, Brewer MD, Chen J, Yang X. Phosphorylation of Daxx by ATM contributes to DNA damage-induced p53 activation. PLoS One. 2013 Aug.8(2):e55813. Pubmedid: 23405218. Pmcid: PMC3566025. Chen J. The Roles of MDM2 and MDMX Phosphorylation in Stress Signaling to p53. Genes Cancer. 2012 Mar.3(3-4):274-282. Pubmedid: 23150760. Pmcid: PMC3494364. Peng L, Ling H, Yuan Z, Fang B, Bloom G, Fukasawa K, Koomen J, Chen J, Lane WS, Seto E. SIRT1 negatively regulates the activities, functions, and protein levels of hMOF and TIP60. Mol Cell Biol. 2012 Jul.32(14):2823-2836. Pubmedid: 22586264. Pmcid: PMC3416197. Wu S, Chen L, Becker A, Schonbrunn E, Chen J. Casein kinase 1α regulates an MDMX intramolecular interaction to stimulate p53 binding. Mol Cell Biol. 2012 Dec.32(23):4821-4832. Pubmedid: 23028042. Pmcid: PMC3497597. Li X, Gilkes D, Li B, Cheng Q, Pernazza D, Lawrence N, Chen J. Abnormal MDMX degradation in tumor cells due to ARF deficiency. Oncogene. 2012 Aug.31(32):3721-3732. Pubmedid: 22120712. Pmcid: PMC3290737.