{"id":40828,"date":"2019-07-01T15:19:06","date_gmt":"2019-07-01T19:19:06","guid":{"rendered":"https:\/\/web.uri.edu\/pharmacy\/?page_id=40828"},"modified":"2020-03-11T10:43:14","modified_gmt":"2020-03-11T14:43:14","slug":"li","status":"publish","type":"page","link":"https:\/\/web.uri.edu\/pharmacy\/research\/li\/","title":{"rendered":"Dr. Deyu Li"},"content":{"rendered":"

Medical Organic Chemistry Laboratory<\/h1>

Located in Lab Module 410 on Level 4 of Avedisian Hall<\/p><\/div><\/div>

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Overview<\/h1><\/p>\n

Dr. Li\u2019s research examines the formation of DNA lesions and subsequent mutations via chemistry and molecular biology techniques. The objective is to identify tumor development at early stage or even before its genesis by mapping out the mutational spectra of various carcinogens. Dr. Li and his team also work with specific molecular inhibitors such as Nitric Oxide and oncometabolites to certain DNA repair enzymes to understand their disruptive effects on cellular defending machineries.<\/p>\n

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Research<\/h1><\/p>\n

Mutational spectra of bulky DNA lesions<\/strong> (Supported by NIEHS as an R01)<\/strong><\/h3>\n

Many environmental toxins damage DNA and cause diseases.  The exposure of cells with DNA damaging agents results in the formation of a host of different DNA lesions, a subset of which can give rise to mutations.  If one were to plot the frequency and type of mutation as a function of the position along a gene, a distribution is generated that is commonly referred to as a mutational spectrum.  It is important for environmental scientists to provide insights into the evolutionary changes that foreshadow tumor development before overt clinical symptoms appear.  This goal is crucial because some diseases, such as tumors, show few clinical symptoms until the disease has reached a late, usually deadly stage.  Early onset genomic biomarkers might enable intervention to eliminate or curtail development of the disease.  The biomarkers of a disease caused by a specific toxin can be obtained by studying the mutational spectra of DNA lesions generated from the toxin.  At the conclusion of this project we will demonstrate the interaction between environmental toxins and the mutational spectra in human genome.  These studies shall utilize in a combination of genetic, chemical, and spectroscopic tools to understand and manipulate biological systems at the molecular level. <\/p>\n

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Inhibitory effect of nitric oxide on DNA repair enzymes <\/strong>(Supported by NIEHS as an R15)<\/strong><\/h3>\n

Nitric oxide (NO), a signaling molecule over produced in the inflammation process, has been reported to induce damage of cell membrane and lead to the accumulation of alkylated DNA adducts, such as 1,N6-ethenoadenine (eA), 3,N4-ethenocytosine (eC).  In this project, we will study a new aspect of nitric oxide\u2019s cellular role in inflammation and cancer: the inhibitory effect of NO on the AlkB family DNA repair enzymes.  The AlkB proteins, a group of Fe(II)\/\u03b1-ketoglutarate-dependent dioxygenases, have been established to repair DNA alkyl lesions by a direct reversal mechanism.  Different homologs of AlkB exist in eukaryotic and prokaryotic species; nine such homologs exist in mammalian cells (ABH1-8 and FTO).  In humans, ABH2 and ABH3 have been identified as DNA repair enzyme and constitute the most effective cellular defense against DNA adducts.  In the preliminary study, we have shown that NO has strong inhibitory effect on AlkB, ABH2 and ABH3.  Electron paramagnetic resonance (EPR) spectroscopic studies also showed NO binds to the Fe(II) ion in the catalytic center of AlkB, thus inhibiting the catalytic O2<\/sub> binding and abolishing the repair activity of AlkB.  The central hypothesis of this project is that NO delivers a \u201ctwo-fold\u201d damage to the cell by not only inducing alkyl DNA damages but also suppressing the AlkB family DNA repair enzymes.  The focus of this project is to study the relationship between DNA repair and NO inhibition at molecular level both in vitro and in cell.  The knowledge gained from those experiments will help us understand the molecular and cellular mechanisms of NO inhibition on DNA repair and provide insights for developing new strategy to prevent and overcome the cellular damage and tumorigenesis.  Overall, these studies will characterize a role of nitric oxide in the pathological processes of inflammation and cancer.  Once again, DNA damage is a primary initiator of many diseases and completion of the proposed studies will have direct relevance to human health.<\/p>\n

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Publications<\/h1><\/p>\n

Complete List of Peer-Reviewed Publications (*corresponding authorship)<\/h4>\n
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    \n
  1. Ke Bian, James C. Delaney, Xianhao Zhou, Deyu Li<\/strong># <\/sup>\u201cBiological evaluation of DNA biomarkers in a chemically defined and site-specific manner\u201d Toxics<\/em>,<\/li>\n
  2. Ke Bian*, Stefan A. P. Lenz*, Qi Tang, Fangyi Chen, Rui Qi, Marco Jost, Catherine L. Drennan, John M. Essigmann, Stacey D. Wetmore#<\/sup>, Deyu Li<\/strong># <\/sup>\u201cDNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine\u201d Nucleic Acids Research<\/em>,<\/li>\n
  3. Jessica L. Wojtaszek*, Nimrat Chatterjiee*, Javaria Najeeb*, Azucena Ramos, Minhee Lee, Ke Bian, Yaohua Xue, Deyu Li<\/strong>, Michael T. Hemann#<\/sup>, Jiyong Hong#<\/sup>, Graham C. Walker#<\/sup>, Pei Zhou#<\/sup> \u201cSmall molecule adjuvant disrupting Rev1-Pol\u03b6 mediated mutagenic translesion synthesis improves chemotherapy\u201d Cell<\/em>, accepted.<\/li>\n
  4. Fangyi Chen*, Qi Tang*, Hang Ma*, Ke Bian, Navindra Seeram, Deyu Li<\/strong># <\/sup>\u201cHydrolyzable tannins are iron chelators that inhibit AlkB family DNA repair enzyme ALKBH2\u201d Chemical Research in Toxicology<\/em>, accepted.<\/li>\n
  5. Ang Cai*, Ke Bian*, Fangyi Chen, Qi Tang, Deyu Li<\/strong>#<\/sup>, Bongsup Cho# <\/sup>\u201cProbing the effect of bulky lesion-Induced replication fork conformational heterogeneity using 4-aminobyphenyl-modified DNA\u201d Molecules<\/em>, 2019<\/strong>, 24<\/em>, 1566.<\/li>\n
  6. Ke Bian*, Fangyi Chen*, Zachary T. Humulock*, Qi Tang, Deyu Li<\/strong># <\/sup>\u201cCopper inhibits the AlkB family DNA repair enzymes under Wilson’s disease condition\u201d Chemical Research in Toxicology<\/em> 2017<\/strong>, 30<\/em>, 1794.<\/li>\n
  7. Qi Tang*, Ang Cai*, Ke Bian, Fangyi Chen, Sravani Adusumalli, Alvin C. Bach II, Fatemeh Akhlaghi, Bongsup Cho, Deyu Li<\/strong># <\/sup>\u201cCharacterization of byproducts from chemical syntheses of oligonucleotides containing 1-methyladenine and 3-methylcytosine\u201d ACS Omega<\/em>, 2017<\/strong>, 2<\/em>, 8205.<\/li>\n
  8. Fangyi Chen*, Ke Bian*, Qi Tang, Bogdan I. Fedeles, Vipender Singh, Zachary T. Humulock, John M. Essigmann, Deyu Li<\/strong># <\/sup>\u201cOncometabolites D- and L-2-hydroxyglutarate inhibit the AlkB family DNA repair enzymes under physiological conditions\u201d Chemical Research in Toxicology<\/em> 2017<\/strong>, 30<\/em>, 1102.<\/li>\n
  9. Fangyi Chen*, Qi Tang*, Ke Bian, Zachary T. Humulock, Xuedong Yang, Marco Jost, Catherine L. Drennan, John M. Essigmann, Deyu Li<\/strong># <\/sup>\u201cThe adaptive response enzyme AlkB preferentially repairs 1-methylguanine and 3-methylthymine adducts in double-stranded DNA\u201d Chemical Research in Toxicology<\/em> 2016<\/strong>, 29<\/em>, 687.<\/li>\n
  10. Bogdan I. Fedeles*, Vipender Singh*, James C. Delaney, Deyu Li#<\/sup><\/strong>, John M. Essigmann#<\/sup> \u201cThe AlkB family of Fe(II)\/\u03b1-Ketoglutarate-dependent dioxygenases: repairing nucleic acid alkylation damage and beyond\u201d Journal of Biological Chemistry <\/em>2015<\/strong>, 290<\/em>, 20734. (Invited for the seventh thematic series on Metals in Biology)<\/li>\n
  11. Chunte S. Peng, Bogdan I. Fedeles, Vipender Singh, Deyu Li<\/strong>, Tiffany Amariuta, John M. Essigmann, Andrei Tokmakoff \u201c2D IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity\u201d Proceedings of the National Academy of Sciences USA<\/em>, 2015<\/strong>, 112<\/em>, 3239.<\/li>\n
  12. Shiou-chi Chang, Bogdan I. Fedeles, Jie Wu, James C. Delaney, Deyu Li<\/strong>, Linlin Zhao, Plamen P. Christov, Emily Yau, Vipender Singh, Marco Jost, Catherine L. Drennan, Lawrence J. Marnett, Carmelo J. Rizzo, Stuart S. Levine, F. Peter Guengerich, John M. Essigmann \u201cNext-generation sequencing reveals the biological significance of the N2,3-ethenoguanine lesion in vivo<\/em>\u201d Nucleic Acids Research<\/em> 2015<\/strong>, 43<\/em>, 5489. (Highlighted as the Breakthrough paper of the journal and also by the MIT News on April 1, 2015)<\/li>\n
  13. Bogdan I. Fedeles, Bret D. Freudenthal, Emily Yau, Vipender Singh, Shiou-chi Chang, Deyu Li<\/strong>, James C. Delaney, Samuel H. Wilson, John M. Essigmann \u201cIntrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer\u201d Proceedings of the National Academy of Sciences USA<\/em> 2015<\/strong>, 112<\/em>, E4571.  (Highlighted by the MIT News on August 7, 2015) <\/li>\n
  14. Deyu Li<\/strong>*, Bogdan I. Fedeles*, Vipender Singh*, Chunte S. Peng*, Katherine J. Silvestre, Jeffrey H. Simpson, Andrei Tokmakoff, John M. Essigmann \u201cTautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside analog 5-aza-5,6-dihydro-deoxycytidine\u201d Proceedings of the National Academy of Sciences USA<\/em> 2014<\/strong>, 111<\/em>, E3252. (Highlighted by the MIT News on July 28, 2014)<\/li>\n
  15. Vipender Singh*, Bogdan I. Fedeles*, Deyu Li<\/strong>*, James C. Delaney, Ivan D. Kozekov, Albena Kozekova, Lawrence J. Marnett, Carmelo J. Rizzo, John M. Essigmann \u201cMechanism of repair of acrolein- and malondialdehyde-derived exocyclic guanine adducts by the \u03b1-ketoglutarate\/Fe(II) dioxygenase AlkB\u201d Chemical Research in Toxicology<\/em> 2014<\/strong>, 27<\/em>, 1619.<\/li>\n
  16. Nidhi Shrivastav, Bogdan I. Fedeles, Deyu Li<\/strong>, James C. Delaney, Lauren E. Frick, James J. Foti, Graham C. Walker, John M. Essigmann \u201cA chemical genetics analysis of the roles of bypass polymerase DinB and DNA repair protein AlkB in processing N<\/em>2<\/sup>-alkylguanine lesions in vivo<\/em>\u201d PLoS ONE<\/em> 2014<\/strong>, 9<\/em>, e94716.<\/li>\n
  17. Vipender Singh, Chunte S. Peng, Deyu Li<\/strong>, Koyel Mitra, Katherine Silvestre, Andrei Tokmakoff, John M. Essigmann \u201cDirect observation of tautomers of oxythiamine and their recognition by an RNA aptamer\u201d ACS Chemical Biology<\/em>, 2014<\/strong>, 9<\/em>, 227.<\/li>\n
  18. Deyu Li<\/strong>, Bogdan I. Fedeles, Nidhi Shrivastav, James C. Delaney, Xuedong Yang, Cintyu Wong, Catherine L. Drennan, John M. Essigmann \u201cRemoval of alkylation DNA adducts from N<\/em>2<\/sup>-alkylguanine and N<\/em>4<\/sup>-alkylcytosine by the adaptive response protein AlkB\u201d Chemical Research in Toxicology<\/em> 2013<\/strong>, 26<\/em>, 1182. (Cover paper, August, 2013)<\/li>\n
  19. Jingqing Zhang, Markita P. Landry, Paul W. Barone, Jong-Ho Kim, Shangchao Lin, Zachary W. Ulissi, Dahua Lin, Bin Mu, Ardemis A. Boghossian, Andrew J. Hilmer, Alina Rwei, Allison C. Hinckley, Sebastian Kruss, Mia A. Shandell, Nitish Nair, Steven Blake, Fatih Sen, Selda Sen, Robert G. Croy, Deyu Li<\/strong>, Kyungsuk Yum, Jin-Ho Ahn, Hong Jin, Daniel A. Heller, John M. Essigmann, Daniel Blankschtein, Michael S. Strano \u201cMolecular recognition using nanotube-adsorbed polymer complexes\u201d Nature<\/em> Nanotechnology<\/em> 2013<\/strong>, 8<\/em>, 959.<\/li>\n
  20. Deyu Li<\/strong>, James C. Delaney, Charlotte M.  Page, Xuedong Yang, Alvin S.  Chen, Cintyu Wong, Catherine L.  Drennan, John M.  Essigmann \u201cExocyclic carbons adjacent to the N<\/em>6<\/sup> of adenine are targets for oxidation by the Escherichia coli<\/em> adaptive response protein AlkB\u201d Journal of the American Chemical Society<\/em> 2012<\/strong>, 134<\/em>, 8896.  (Highlighted by Chemical Research in Toxicology<\/em> 2012<\/strong>, 25<\/em>, 1286.)<\/li>\n
  21. Gerald Kagan, Weibin Li, Deyu Li<\/strong>, Russell Hopson, Paul G. Williard \u201cCharacterization of dimeric chiral lithium amide structures derived from N<\/em>-isopropyl-O<\/em>-triisopropylsilyl valinol\u201d Journal of the American Chemical Society<\/em> 2011<\/strong>, 133<\/em>, 6596.<\/li>\n
  22. James I. Mullins, Laura Heath, James P. Hughes, Jessica Kicha, Sheila Styrchak, Kim Wong, Ushnal Rao, Alexis Hansen, Kevin S. Harris, Jean-Pierre Laurent, Deyu Li<\/strong>, Jeffrey H. Simpson, John M. Essigmann, Lawrence A. Loeb, Jeffrey Parkins \u201cMutations resulting from viral decay acceleration of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461\u201d PLoS ONE<\/em> 2011<\/strong>, 6<\/em>, e15135.<\/li>\n
  23. Deyu Li<\/strong>, James C. Delaney, Charlotte M.  Page, Alvin S.  Chen, Cintyu Wong, Catherine L.  Drennan, John M.  Essigmann \u201cRepair of DNA alkylation damage by the Escherichia coli<\/em> adaptive response protein AlkB as studied by ESI-TOF mass spectrometry\u201d Journal of Nucleic Acids<\/em> 2010<\/strong>, 369434.  (Invited submission for a special issue on \u201cDNA Damage, Mutagenesis, and DNA Repair.\u201d)<\/li>\n
  24. Nidhi Shrivastav<\/a>, Deyu Li<\/strong>, John M. Essigmann \u201cChemical biology of mutagenesis and DNA repair: cellular responses to DNA alkylation\u201d Carcinogenesis<\/em> 2010<\/strong>, 31<\/em>, 59.  (Invited submission for a special issue to celebrate the 30th<\/sup> anniversary of Carcinogenesis<\/em>.)<\/li>\n
  25. Deyu Li<\/strong>, Gerald Kagan, Russell Hopson, Paul G. Williard \u201cFormula weight prediction by internal reference diffusion-ordered NMR spectroscopy (DOSY)\u201d Journal of the American Chemical Society<\/em> 2009<\/strong>, 131<\/em>, 5627.<\/li>\n
  26. Deyu Li<\/strong>, Ivan Keresztes, Russell Hopson, Paul G. Williard \u201cCharacterization of reactive intermediates by multinuclear diffusion-ordered NMR spectroscopy (DOSY)\u201d Accounts of Chemical Research<\/em> 2009<\/strong>, 42<\/em>, 270.<\/li>\n
  27. Deyu Li<\/strong>, Chengzao Sun, Jia Liu, Paul G. Williard \u201cCharacterization of a chiral enolate aggregate and observation of 6<\/sup>Li-1<\/sup>H scalar coupling\u201d Journal of the American Chemical Society<\/em> 2008<\/strong>, 130<\/em>, 11726.<\/li>\n
  28. Deyu Li<\/strong>, Chengzao Sun, Jia Liu, Russell Hopson, Weibin Li, Paul G. Williard \u201cAggregation studies of complexes containing a chiral lithium amide and n<\/em>-butyllithium\u201d Journal of Organic Chemistry<\/em> 2008<\/strong>, 73<\/em>, 2373.<\/li>\n
  29. Jia Liu, Deyu Li<\/strong>, Chengzao Sun, Paul G. Williard \u201cAnalysis of an asymmetric addition with a 2:1 mixed lithium amide\/n<\/em>-butyllithium aggregate\u201d Journal of Organic Chemistry<\/em> 2008<\/strong>, 73<\/em>, 4045.<\/li>\n
  30. Deyu Li<\/strong>, Russell Hopson, Weibin Li, Jia Liu, Paul G. Williard \u201c13<\/sup>C INEPT diffusion-ordered NMR spectroscopy (DOSY) with internal references\u201d Organic Letters<\/em> 2008<\/strong>, 10<\/em>, 909.<\/li>\n
  31. Lili Ma, Russell Hopson, Deyu Li<\/strong>, Yong Zhang, Paul G. Williard \u201cSynthesis and structural characterization of the bis(diisopropylamino)boron enolate of tert<\/em>-butyl methyl ketone\u201d Organometallics<\/em> 2007<\/strong>, 26<\/em>, 5834.<\/li>\n
  32. Jingguang Yu, Xiuzhen Luo, Lan Sun, Deyu Li<\/strong>, Wenhua Huang, Chunyu Liu \u201cChemical constituents from the seeds of Annona squamosa<\/em>\u201d Acta Pharmaceutica Sinica<\/em> 2005<\/strong>, 40<\/em>, 153.<\/li>\n
  33. Wenhua Huang, Jingguang Yu, Lan Sun, Baolin Guo, Deji Basang, Deyu Li<\/strong> \u201cStudies on chemical constituents of the seeds from Xanthium sibiricum<\/em>\u201d China Journal of Chinese Materia Medica<\/em> 2005<\/strong>, 30<\/em>, 1027.<\/li>\n
  34. Lan Sun, Jiuxiang Zhu, Jingguang Yu, Donglei Yu, Deyu Li<\/strong>, Lidong Zhou \u201cChemical constituents from the seeds of Annona glabra<\/em> (Annonaceae)\u201d Acta Pharmaceutica Sinica<\/em> 2003<\/strong>, 38<\/em>, 32.<\/li>\n
  35. Jingguang Yu, Tongmei Li, Lan Sun, Xiuzhen Luo, Wei Ding, Deyu Li<\/strong> \u201cneo<\/em>-Lignans and hemiterpenoid from the seeds of Artabostrys hexapetalus<\/em> (Annonaceae)\u201d Journal of Chinese Pharmaceutical Sciences<\/em> 2002<\/strong>, 11<\/em>, <\/li>\n
  36. Deyu Li<\/strong>, Jingguang Yu, Jiuxiang Zhu, Donglei Yu, Xiuzhen Luo, Lan Sun, Shilin Yang \u201cAnnonaceous acetogenins of the seeds from Annona muricata<\/em>\u201d Journal of Asian natural products research<\/em> 2001<\/strong>, 3<\/em>, 267.<\/li>\n
  37. Lan Sun, Jingguang Yu, Deyu Li<\/strong>, Jin Li, Xuedong Yang, Shilin Yang \u201cDetermination of Annonaceous acetogenins in annonaceae plants by HPLC\u201d Acta Pharmaceutica Sinica<\/em> 2001<\/strong>, 36<\/em>, 683.<\/li>\n
  38. Jingguang Yu, Tongmei Li, Lan Sun, Xiuzhen Luo, Wei Ding, Deyu Li<\/strong> \u201cStudies on chemical constituents of the seeds from Atrabotrys hexapetalus<\/em> (Annonaceae)\u201d Acta Pharmaceutica Sinica<\/em> 2001<\/strong>, 36<\/em>, 281.<\/li>\n
  39. Jiuxiang Zhu, Jingguang Yu, Xiuzhen Luo, Lan Sun, Deyu Li<\/strong>, Shilin Yang \u201cAlkaloids from leaves of Goniothalamus cheliensis<\/em>\u201d Chinese Traditional and Herbal Drugs<\/em>, 2000<\/strong>, 31<\/em>, 813.<\/li>\n
  40. Deyu Li<\/strong>, Jingguang Yu, Xiuzhen Luo, Lan Sun, Shilin Yang \u201cMuricatenol, a linear acetogenin from Annona Muricata <\/em>(Annonaceae)\u201d Chinese Chemical Letters<\/em> 2000<\/strong>, 11<\/em>, 239.<\/li>\n
  41. Kun Zou, Yuying Zhao, Deyu Li<\/strong>, Feng Xu, Junhua Zheng, Ruyi Zhang \u201cHydrophobic constituents from Albizia julibrissin<\/em>\u201d Journal of Beijing Medical University<\/em> 1999<\/strong>, 31<\/em>, 32.<\/li>\n
  42. Kun Zou, Yuying Zhao, Bin Wang, Deyu Li<\/strong>, Shaoqing Cai, Ruyi Zhang \u201cStructural identification of two diastereoisomeric saponins from Albizia Julibrissin<\/em>\u201d Chemical Journal of Chinese Universities<\/em>, 1999<\/strong>, 20<\/em>, 1877.<\/li>\n
  43. Hong Liang, Yuying Zhao, Deyu Li<\/strong>, Li Tan, Jie Huang \u201cProgress of chemical constituents and pharmacological activities of the plants in Bupleurum<\/em>\u201d World Phytomedicines<\/em> 1999<\/strong>, 14<\/em>, 191.<\/li>\n<\/ol>\n

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    Research Team<\/h1><\/p>\n