Jian Jin, PhD
- PROFESSOR | Pharmacological Sciences
- PROFESSOR | Oncological Sciences
Research Topics:Cancer, Chromatin, Drug Design and Discovery, Membrane Proteins/Channels, Schizophrenia
Dr. Jian Jin received a B.S. degree in chemistry from University of Science and Technology of China in 1991 and a Ph.D. degree in organic chemistry from the Pennsylvania State University in 1997. After completing a postdoctoral training at the Ohio State University, Dr. Jin joined GlaxoSmithKline as a medicinal chemist in 1998 and had been a manager of medicinal chemistry from 2003 to 2008. In 2008, Dr. Jin joined the Division of Chemical Biology and Medicinal Chemistry at the University of North Carolina at Chapel Hill (UNC – CH) as an Associate Professor. He had also served as an Associate Director of medicinal chemistry in the Center for Integrative Chemical Biology and Drug Discovery at UNC – CH from 2008 to 2014. In 2014, Dr. Jin was recruited to the Icahn School of Medicine at Mount Sinai (Mount Sinai) as a Professor with Tenure. He is currently a Professor of Structural and Chemical Biology, Professor of Oncological Sciences, and Professor of Pharmacology and Systems Therapeutics at Mount Sinai. Since 2008, Dr. Jin’s laboratory has focused on discovering selective inhibitors of histone methyltransferases and functionally selective ligands of G protein-coupled receptors. To date, Dr. Jin has published more than 100 research papers and delivered more than 70 invited talks. He is also an inventor of 10 issued U.S. patents and 37 published PCT patent applications.
Complete list of published work in PubMed
Google scholar citations
Multi-Disciplinary Training AreaBiophysics and Systems Pharmacology [BSP]
BS, University of Science and Technology of China
PhD, Pennsylvania State University
Postdoc, Ohio State University
Discovery of Functionally Selective Ligands of GPCRs
G protein-coupled receptors (GPCRs) signal not only via canonical pathways involving heterotrimeric large G proteins, but also via non-canonical G protein-independent interactions with other signaling proteins including beta-arrestins. The process by which GPCR ligands differentially modulate canonical and non-canonical signal transduction pathways is a phenomenon known as “functional selectivity” (also knows as signaling bias). Such functionally selective ligands (also known as biased ligands) preferentially engage either canonical or non-canonical GPCR pathways. The discovery of ligands with discrete functional selectivity profiles will be extremely useful for elucidating the key signal transduction pathways essential for both the therapeutic actions and side-effects of drugs. The Jin lab has been actively engaged in generating functionally selective ligands of GPCRs.
Discovery of Selective Inhibitors for Histone Methyltransferases
Post-translational modifications (PTMs) of histones play a critical role in diverse biological processes including chromatin compaction, gene expression, transcriptional regulation, and cell differentiation. Among a myriad of PTMs, histone methylation catalyzed by histone methyltransferases (HMTs) has been increasingly recognized as a major signaling mechanism in eukaryotic cells. HMTs are divided into two categories: lysine methyltransferases (PKMTs) and arginine methyltransferases (PRMTs), More than 50 PKMTs and 9 PRMTs have been identified. Mounting evidence suggests that HMTs play crucial roles in various human diseases. To create high quality selective inhibitors of HMTs, the Jin lab has taken a systematic approach by targeting the HMT substrate binding groove, cofactor binding site, and potential allosteric binding site(s).
Liu F, Chen X, Allali-Hassani A, Quinn AM, Wasney GA, Dong A, Barsyte D, Kozieradzki I, Senisterra G, Chau I, Siarheyeva A, Kireev DB, Jadhav A, Herold JM, Frye SV, Arrowsmith CH, Brown PJ, Simeonov A, Vedadi M, Jin J. Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a. Journal of medicinal chemistry 2009 Dec; 52(24).
Johnson SM, Torrice CD, Bell JF, Monahan KB, Jiang Q, Wang Y, Ramsey MR, Jin J, Wong KK, Su L, Zhou D, Sharpless NE. Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. The Journal of clinical investigation 2010 Jul; 120(7).
Liu F, Chen X, Allali-Hassani A, Quinn AM, Wigle TJ, Wasney GA, Dong A, Senisterra G, Chau I, Siarheyeva A, Norris JL, Kireev DB, Jadhav A, Herold JM, Janzen WP, Arrowsmith CH, Frye SV, Brown PJ, Simeonov A, Vedadi M, Jin J. Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines. Journal of medicinal chemistry 2010 Aug; 53(15).
Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin J. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nature chemical biology 2011 Aug; 7(8).
Liu F, Barsyte-Lovejoy D, Allali-Hassani A, He Y, Herold JM, Chen X, Yates CM, Frye SV, Brown PJ, Huang J, Vedadi M, Arrowsmith CH, Jin J. Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines. Journal of medicinal chemistry 2011 Sep; 54(17).
Allen JA, Yost JM, Setola V, Chen X, Sassano MF, Chen M, Peterson S, Yadav PN, Huang XP, Feng B, Jensen NH, Che X, Bai X, Frye SV, Wetsel WC, Caron MG, Javitch JA, Roth BL, Jin J. Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proceedings of the National Academy of Sciences of the United States of America 2011 Nov; 108(45).
Huang HS, Allen JA, Mabb AM, King IF, Miriyala J, Taylor-Blake B, Sciaky N, Dutton JW, Lee HM, Chen X, Jin J, Bridges AS, Zylka MJ, Roth BL, Philpot BD. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 2012 Jan; 481(7380).
Duncan JS, Whittle MC, Nakamura K, Abell AN, Midland AA, Zawistowski JS, Johnson NL, Granger DA, Jordan NV, Darr DB, Usary J, Kuan PF, Smalley DM, Major B, He X, Hoadley KA, Zhou B, Sharpless NE, Perou CM, Kim WY, Gomez SM, Chen X, Jin J, Frye SV, Earp HS, Graves LM, Johnson GL. Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer. Cell 2012 Apr; 149(2).
Siarheyeva A, Senisterra G, Allali-Hassani A, Dong A, Dobrovetsky E, Wasney GA, Chau I, Marcellus R, Hajian T, Liu F, Korboukh I, Smil D, Bolshan Y, Min J, Wu H, Zeng H, Loppnau P, Poda G, Griffin C, Aman A, Brown PJ, Jin J, Al-Awar R, Arrowsmith CH, Schapira M, Vedadi M. An allosteric inhibitor of protein arginine methyltransferase 3. Structure (London, England : 1993) 2012 Aug; 20(8).
Korboukh I, Hull-Ryde EA, Rittiner JE, Randhawa AS, Coleman J, Fitzpatrick BJ, Setola V, Janzen WP, Frye SV, Zylka MJ, Jin J. Orally active adenosine A(1) receptor agonists with antinociceptive effects in mice. Journal of medicinal chemistry 2012 Jul; 55(14).
Chen X, Sassano MF, Zheng L, Setola V, Chen M, Bai X, Frye SV, Wetsel WC, Roth BL, Jin J. Structure-functional selectivity relationship studies of β-arrestin-biased dopamine D₂ receptor agonists. Journal of medicinal chemistry 2012 Aug; 55(16).
James LI, Barsyte-Lovejoy D, Zhong N, Krichevsky L, Korboukh VK, Herold JM, MacNevin CJ, Norris JL, Sagum CA, Tempel W, Marcon E, Guo H, Gao C, Huang XP, Duan S, Emili A, Greenblatt JF, Kireev DB, Jin J, Janzen WP, Brown PJ, Bedford MT, Arrowsmith CH, Frye SV. Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain. Nature chemical biology 2013 Mar; 9(3).
Liu F, Li F, Ma A, Dobrovetsky E, Dong A, Gao C, Korboukh I, Liu J, Smil D, Brown PJ, Frye SV, Arrowsmith CH, Schapira M, Vedadi M, Jin J. Exploiting an allosteric binding site of PRMT3 yields potent and selective inhibitors. Journal of medicinal chemistry 2013 Mar; 56(5).
Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C, Huang XP, Kuznetsova E, Rougie M, Jiang A, Pattenden SG, Norris JL, James LI, Roth BL, Brown PJ, Frye SV, Arrowsmith CH, Hahn KM, Wang GG, Vedadi M, Jin J. An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS chemical biology 2013; 8(6).
Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh V, Huang XP, Allali-Hassani A, Janzen WP, Roth BL, Frye SV, Arrowsmith CH, Brown PJ, Vedadi M, Jin J. Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. Journal of medicinal chemistry 2013 Nov; 56(21).
Zhou B, Damrauer JS, Bailey ST, Hadzic T, Jeong Y, Clark K, Fan C, Murphy L, Lee CY, Troester MA, Miller CR, Jin J, Darr D, Perou CM, Levine RL, Diehn M, Kim WY. Erythropoietin promotes breast tumorigenesis through tumor-initiating cell self-renewal. The Journal of clinical investigation 2014 Feb; 124(2).
Lehnertz B, Pabst C, Su L, Miller M, Liu F, Yi L, Zhang R, Krosl J, Yung E, Kirschner J, Rosten P, Underhill TM, Jin J, Hébert J, Sauvageau G, Humphries RK, Rossi FM. The methyltransferase G9a regulates HoxA9-dependent transcription in AML. Genes & development 2014 Feb; 28(4).
Konze KD, Pattenden SG, Liu F, Barsyte-Lovejoy D, Li F, Simon JM, Davis IJ, Vedadi M, Jin J. A chemical tool for in vitro and in vivo precipitation of lysine methyltransferase G9a. ChemMedChem 2014 Mar; 9(3).
Wright BD, Loo L, Street SE, Ma A, Taylor-Blake B, Stashko MA, Jin J, Janzen WP, Frye SV, Zylka MJ. The lipid kinase PIP5K1C regulates pain signaling and sensitization. Neuron 2014 May; 82(4).
Sundriyal S, Malmquist NA, Caron J, Blundell S, Liu F, Chen X, Srimongkolpithak N, Jin J, Charman SA, Scherf A, Fuchter MJ. Development of diaminoquinazoline histone lysine methyltransferase inhibitors as potent blood-stage antimalarial compounds. ChemMedChem 2014 Oct; 9(10).
Ma A, Yu W, Li F, Bleich RM, Herold JM, Butler KV, Norris JL, Korboukh V, Tripathy A, Janzen WP, Arrowsmith CH, Frye SV, Vedadi M, Brown PJ, Jin J. Discovery of a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8. Journal of medicinal chemistry 2014 Aug; 57(15).
Ma A, Yu W, Xiong Y, Butler KV, Brown PJ, Jin J. Structure-activity Relationship Studies of SETD8 Inhibitors. MedChemComm 2014;: DOI: 10.1039/C4MD00317A.
Xu B, On DM, Ma A, Parton T, Konze KD, Pattenden SG, Allison DF, Cai L, Rockowitz S, Liu S, Liu Y, Li F, Vedadi M, Frye SV, Garcia BA, Zheng D, Jin J, Wang GG. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood 2014 Nov;.
Kaniskan HU, Jin J. Chemical Probes of Histone Lysine Methyltransferases. ACS chemical biology 2014 Nov;.
Kaniskan HU, Konze KD, Jin J. Selective Inhibitors of Protein Methyltransferases. Journal of medicinal chemistry 2014 Dec;.
Liu C, Yu Y, Liu F, Wei X, Wrobel JA, Gunawardena HP, Zhou L, Jin J, Chen X. A chromatin activity-based chemoproteomic approach reveals a transcriptional repressome for gene-specific silencing. Nature communications 2014 Dec; 5.
Katona BW, Liu Y, Ma A, Jin J, Hua X. EZH2 inhibition enhances the efficacy of an EGFR inhibitor in suppressing colon cancer cells. Cancer biology & therapy 2014 Dec; 15(12).
Chen X, Choo H, Huang XP, Yang X, Stone O, Roth B, Jin J. The First Structure-activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). ACS chemical neuroscience 2015 Jan;.
Kaniskan HU, Szewczyk MM, Yu Z, Eram MS, Yang X, Schmidt K, Luo X, Dai M, He F, Zang I, Lin Y, Kennedy S, Li F, Dobrovetsky E, Dong A, Smil D, Min SJ, Landon M, Lin-Jones J, Huang XP, Roth BL, Schapira M, Atadja P, Barsyte-Lovejoy D, Arrowsmith CH, Brown PJ, Zhao K, Jin J, Vedadi M. A Potent, Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3). Angewandte Chemie (International ed. in English) 2015 Feb;.
Stuhlmiller TJ, Miller SM, Zawistowski JS, Nakamura K, Beltran AS, Duncan JS, Angus SP, Collins KA, Granger DA, Reuther RA, Graves LM, Gomez SM, Kuan PF, Parker JS, Chen X, Sciaky N, Carey LA, Earp HS, Jin J, Johnson GL. Inhibition of Lapatinib-Induced Kinome Reprogramming in ERBB2-Positive Breast Cancer by Targeting BET Family Bromodomains. Cell reports 2015 Apr; 11(3).
Abou El Hassan M, Huang K, Eswara MB, Zhao M, Song L, Yu T, Liu Y, Liu JC, McCurdy S, Ma A, Wither J, Jin J, Zacksenhaus E, Wrana JL, Bremner R. Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways. PloS one 2015; 10(6).
Xu B, Konze KD, Jin J, Wang GG. Targeting EZH2 and PRC2 dependence as novel anticancer therapy. Experimental hematology 2015 Aug; 43(8).
Wang L, Xie L, Ramachandran S, Lee Y, Yan Z, Zhou L, Krajewski K, Liu F, Zhu C, Chen DJ, Strahl BD, Jin J, Dokholyan NV, Chen X. Non-canonical Bromodomain within DNA-PKcs Promotes DNA Damage Response and Radioresistance through Recognizing an IR-Induced Acetyl-Lysine on H2AX. Chemistry & biology 2015 Jul; 22(7).
Park SM, Chen M, Schmerberg CM, Dulman RS, Rodriguiz RM, Caron MG, Jin J, Wetsel WC. Effects of β-Arrestin-Biased Dopamine D2 Receptor Ligands on Schizophrenia-Like Behavior in Hypoglutamatergic Mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2015 Jul;.
Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O'Hagan RC, Overington JP, Owen DR, Rosenberg SH, Roth B, Ross R, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ. The promise and peril of chemical probes. Nature chemical biology 2015 Jul; 11(8).
Simon JM, Parker JS, Liu F, Rothbart SB, Ait-Si-Ali S, Strahl BD, Jin J, Davis IJ, Mosley AL, Pattenden SG. A Role for Widely Interspaced Zinc Finger (WIZ) in Retention of the G9a Methyltransferase on Chromatin. The Journal of biological chemistry 2015 Sep;.
Wallace BD, Roberts AB, Pollet RM, Ingle JD, Biernat KA, Pellock SJ, Venkatesh MK, Guthrie L, O'Neal SK, Robinson SJ, Dollinger M, Figueroa E, McShane SR, Cohen RD, Jin J, Frye SV, Zamboni WC, Pepe-Ranney C, Mani S, Kelly L, Redinbo MR. Structure and Inhibition of Microbiome β-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity. Chemistry & biology 2015 Sep;.
Huang XP, Karpiak J, Kroeze WK, Zhu H, Chen X, Moy SS, Saddoris KA, Nikolova VD, Farrell MS, Wang S, Mangano TJ, Deshpande DA, Jiang A, Penn RB, Jin J, Koller BH, Kenakin T, Shoichet BK, Roth BL. Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65. Nature 2015 Nov;.
Eram MS, Shen Y, Szewczyk M, Wu H, Senisterra G, Li F, Butler KV, Kaniskan HU, Speed BA, Dela Seña C, Dong A, Zeng H, Schapira M, Brown PJ, Arrowsmith CH, Barsyte-Lovejoy D, Liu J, Vedadi M, Jin J. A Potent, Selective and Cell-active Inhibitor of Human Type I Protein Arginine Methyltransferases. ACS chemical biology 2015 Nov;.
Agarwal P, Alzrigat M, Párraga AA, Enroth S, Singh U, Ungerstedt J, Österborg A, Brown PJ, Ma A, Jin J, Nilsson K, Öberg F, Kalushkova A, Jernberg-Wiklund H. Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target. Oncotarget 2016 Jan;.
Wagner T, Greschik H, Burgahn T, Schmidtkunz K, Schott AK, McMillan J, Baranauskienė L, Xiong Y, Fedorov O, Jin J, Oppermann U, Matulis D, Schüle R, Jung M. Identification of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening platform. Nucleic acids research 2016 Feb;.
Butler KV, Bohn K, Hrycyna CA, Jin J. Non-substrate based, small molecule inhibitors of the human isoprenylcysteine carboxyl methyltransferase. MedChemComm 2016;: DOI: 10.1039/c6md00130k.
Rialdi A, Campisi L, Zhao N, Lagda AC, Pietzsch C, Ho JS, Martinez-Gil L, Fenouil R, Chen X, Edwards M, Metreveli G, Jordan S, Peralta Z, Munoz-Fontela C, Bouvier N, Merad M, Jin J, Weirauch M, Heinz S, Benner C, van Bakel H, Basler C, García-Sastre A, Bukreyev A, Marazzi I. Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation. Science (New York, N.Y.) 2016 Apr;: DOI: 10.1126/science.aad7993.