Photo of Danzhou Yang
Danzhou Yang
Associate Dean for Graduate Programs
Phone: 765-494-8148
Specialization: Anticancer drug discovery, Structure-based rational drug design, DNA G-quadruplex, NMR, Computer modeling
BS, University of Science and Technology of China, Molecular and Cell Biology, 1989
PhD, University of Illinois at Urbana-Champaign, Biophysics, 1996
Postdoc, University of Kentucky, Pharmaceutical Sciences, 1996-99

Currently Accepting Students

Lab website:

Most front line anticancer agents are DNA-targeted small molecules which are highly potent but less selective. Cancer-specific molecular targets have become a frontier for new anticancer drug development. My research program focuses on structures and functions of cancer-specific DNA molecular targets and structure-based rational design of new anticancer drugs. Our goal is to combine the potential of DNA-interactive anticancer compounds with the selectivity properties of molecular-targeted approaches. We work on a number of DNA molecular targets for cancer therapeutics, including DNA secondary structures such as G-quadruplexes, their biological functions and molecular interactions with small molecules and proteins, as well as targeting DNA binding of transcription factors by DNA bis-intercalating drugs. Research in my laboratory involves a variety of biophysical, biochemical, molecular and cellular biology methods, in particular high-field NMR spectroscopy. NMR represents a major method for structural study of biologically relevant DNA secondary structures.

DNA G-quadruplex secondary structures and functions. DNA G-quadruplexes are novel DNA secondary structures formed in biologically important Guanine-rich regions in human genome. G-quadruplexes can readily form under physiological conditions and exhibit great structural diversity. G-quadruplexes formed in human oncogene promoters provide a potential means to modulate oncogene transcription, while G-quadruplexes formed in the human telomeres can inhibit the cancer-specific enzyme telomerase.  We seek to understand the molecular structures and functions of the biologically relevant DNA G-quadruplexes, including those formed in the proximal promoter regions of human oncogenes such as c-MYC, bcl-2, and PDGFR-b, as well as those formed in human telomeres. Delineating the molecular level details of the biologically relevant G-quadruplexes and their drug and protein complexes is important for the evaluation of their potential as cancer therapeutic targets as well as for structure-based rational drug design.

Interactions of DNA G-quadruplexes with small molecules and rational drug design. The biologically relevant DNA G-quadruplexes, in particular those formed in human oncogene promoters and telomere, are emerging as promising new molecular targets for cancer therapeutics. We seek to discover and develop small molecular anticancer drugs that target the DNA G-quadruplexes using a combination of biochemical, biophysical and cellular methods. We are working to delineate the molecular level details of small molecule interactions with biologically relevant G-quadruplexes, which is important for understanding the mechanisms of action of small molecules and for structure-based rational design of quadruplex-targeted small molecule drugs.

Protein interactions of DNA G-quadruplexes. Two proteins have recently been discovered to interact with the c-MYC promoter G-quadruplex and be involved in c-MYC gene regulation. Nucleolin specifically binds and stabilizes the c-MYC G-quadruplex and functions as a transcription repressor, while NM23-H2 destabilizes the c-MYC G-quadruplex by binding to the single-stranded DNA and functions as a transcription activator. We are working on delineating the interactions of these proteins with the c-MYC G-quadruplex at the molecular level to understand their functions and potential for small molecule targeting.

Targeting DNA binding of transcription factors by novel DNA bis-intercalators. The anticancer drug XR5944, a small molecule bis-phenazine initially developed by the Xenova LTD (UK), shows exceptional anticancer activity both in vitro and in vivo. Originally developed as a dual inhibitor of topoisomerases I/II, the primary mechanism of XR5944 action has later been shown to be related with transcription inhibition. Recent study from our lab has shown that XR5944 exhibits a novel-binding mode in the DNA major groove. Furthermore, XR5944 is shown to be a potent inhibitor of several DNA transcription factors, such as estrogen receptor (ER), by inhibiting their DNA binding. We are working on the determination of the precise mechanisms by which XR5944 and its derivatives inhibit estrogen signaling in human breast cancer cells. Inhibition of ER-signaling through interference with ER binding to its consensus estrogen receptor element ERE DNA represents a novel approach to overcome limitations associated with current estrogen-dependent therapeutic modalities. This information can provide a basis for the rational use of XR56944 or its derivatives in the clinical setting, as well as the development of transcription factor inhibitors in general.

Lab Members
Adam J. Buric (Graduate Student)
Luying Chen (Graduate Student)
Sarah Dagher (Graduate Student)
Mercedes Catherine DeMoss (Graduate Student)
Jonathan Dickerhoff (Post-Doctoral Research Associate)
Yichen Han (Graduate Student)
Kristen Lee Huseman (PULSE Graduate Student)
Jinho Jang (Graduate Student)
Saburo Sakai (Adjunct Professor)
Representative Publications

Wu G, Tillo D, Ray S, Chang T-C, Schneekloth JS,  Vinson C,  Yang D. Custom G4 (2020) “Microarrays Reveal Selective G-Quadruplex Recognition of Small Molecule BMVC: A Large-Scale Assessment of Ligand Binding Selectivity” Molecules 2020, 25(15):3465. doi: 10.3390/molecules25153465. PMID: 32751510. PMCID: PMC7436161.

Wang K, Dickerhoff J, Wu G, Yang D. (2020) “PDGFR- β Promoter Forms a Vacancy G-Quadruplex that Can be Filled-in by dGMP: Solution Structure and Molecular Recognition of Guanine Metabolites and Drugs.” J. Am. Chem. Soc. 142(11):5204-5211. doi: 10.1021/jacs.9b12770.

Liu W, Lin C, Wu G, Wang K, Chang TC, Yang D. (2019) “Solution structures of 1:1 and 2:1 complexes of a fluorescent carbazole BMVC and MYC promoter G-quadruplex: Insights into conformation adjustment towards G4-recognition” Nucleic Acids Res. 2019, 47 (22), 11931–11942.

Wu G, Xing Z, Tran EJ, Yang D. (2019) DDX5 helicase resolves G-quadruplex and is involved in MYC gene transcriptional activation. PNAS, 116 (41), 20453-20461. DOI: 10.1073/pnas.1909047116. PMID: 31548374.

Wang K, Elsayed MSA, Wu G, Deng D, Cushman M, Yang D. (2019) Indenoisoquinoline Topoisomerase Inhibitors Strongly Bind and Stabilize the MYC Promoter G-Quadruplex and Downregulate MYC. J. Am. Chem. Soc. 141(28), 11059-11070. DOI: 10.1021/jacs.9b02679. PMID: 31283877. Press release: Purdue University Research Foundation News,; Science Daily,;, EurekAlert!, Science News Release, News Medical, ecancer, etc.

Yang D. (2019) G-Quadruplex DNA and RNA, Methods Mol Biol. 2035:1-24. doi: 10.1007/978-1-4939-9666-7_1. PMID:31444741.

Wang K, Flaherty DP, Chen L, Yang D. (2019) High-throughput Screening of G-Quadruplex Ligands by FRET Assay. Methods Mol Biol. 2035:323-331. DOI: 10.1007/978-1-4939-9666-7_19. PMID: 31444759.

Onel B, Wu G, Sun D, Lin C, Yang D. (2019) Electrophoretic Mobility Shift Assay and Dimethyl Sulfate Footprinting for Characterization of G-Quadruplexes and G-Quadruplex-Protein Complexes. Methods Mol Biol. 2035:201-222. DOI: 10.1007/978-1-4939-9666-7_11. PMID: 31444751.

Lin C, Dickerhoff J, Yang D. (2019) NMR Studies of G-Quadruplex Structures and G-Quadruplex-interactive Compounds. Methods Mol Biol. 2035:157-176. doi: 10.1007/978-1-4939-9666-7_9. PMID:31444749.

Wu G, Chen L, Liu W, Yang D. (2019) Molecular Recognition of the Hybrid-Type G-Quadruplexes in Human Telomeres. Molecules 2019, 24(8):1578. doi: 10.3390/molecules24081578. PMID: 31013622. PMCID: PMC6514847.

Deng N, Xia J, Wickstrom L, Lin C, Wang K, He P, Yin Y, Yang D. (2019) Ligand Selectivity in the Recognition of Protoberberine Alkaloids by Hybrid-2 Human Telomeric G-Quadruplex: Binding Free Energy Calculation, Fluorescence Binding, and NMR Experiments. Molecules 24(8):1574. doi: 10.3390/molecules24081574. PMID: 31010072. PMCID:PMC6515380.

Sakai S, Yang D, Yasuda T, Akiyama K, Kuga T, Kano A, Shiraishi F, Amekawa S, Ohtsuka S, Nakaguchi K, Yamaguchi S. (2019) Pulsed terahertz radiation for sensitive quantification of carbonate minerals. ACS Omega 4(2):2702-2707, DOI: 10.1021/acsomega8b03311, PMID: 31459506. PMCID:PMC6648234.

Dickerhoff J, Onel B, Chen L, Chen Y, Yang D. (2019) Solution Structure of a MYC Promoter G-Quadruplex with 1:6:1 Loop Length. ACS Omega, 4 (2), 2533–2539, DOI: 10.1021/acsomega8b03580, PMID: 30842981. PMCID: PMC6396123.

Liu W, Zhong YF, Liu LY, Zeng W, Wang F, Yang D,* Mao ZW.* (2018) Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding. Nature Communications 9, 3496, DOI: 10.1038/s41467-018-05810-4, PMID: 30158518. PMCID:PMC6115404.

Fu X, Guo C, Yang D, Zhang Y. (2018) Investigation of default mode networks in rhesus macaque brain with 7.0 T resting state fMRI. Chinese J. Medical Imaging Technol, 34(6):801-806, DOI: 10.13929/j.1003-3289.201709141.

Lin C, Wu G, Wang K, Onel B, Sakai S, Yang D. (2018) Molecular Recognition of the Hybridâ��2 Human Telomeric Gâ��quadruplex by Epiberberine: Insights into Conversion of Telomeric G-quadruplex Structures. Angew. Chem. Int. Ed. (57),10888 –10893, DOI: 10.1002/anie.201804667, PMID: 29888501, PMCID:PMC6192034. F1000Prime Recommendation. DOI: 10.3410/f.733432559.793547061.

Onel B, Carver M, Agrawal P, Hurley LH, Yang D. (2018) The 3′-End of the PDGFR-β Core Promoter Nuclease Hypersensitive Element Forms a Mixture of Two Unique End-Insertion G-Quadruplexes. Biochim Biophys Acta Gen Subj., 1862(4):846-854, DOI: 10.1016/j.bbagen.2017.12.011, PMID: 29288770. PMCID: PMC6183060.

Deng N, Wickstrom L, Cieplak P, Lin C, Yang D. (2017) Resolving the Ligand Binding Specificity in c-MYC G-Quadruplex DNA: Absolute Binding Free Energy Calculations and SPR Experiment. J. Phys. Chem. B, 121(46):10484-10497, DOI: 10.1021/acs.jpcb.7b09406, PMID: 29086571. PMCID: PMC5825213.

Sakai S, Matsuda S, Hikida T, Shimono A, McManus B, Zahniser M, Nelson D, Dettman D, Yang D, Ohkouchi N. (2017) High-precision simultaneous 18O/16O, 13C/12C and 17O/16O analyses for microgram quantities of CaCO3 by tunable infrared laser absorption spectroscopy. Anal Chem 7;89(21):11846-11852, DOI: 10.1021/acs.analchem.7b03582, PMID: 28937751. PMCID: PMC6152922.

Kaiser CE, Van Ert NA, Agrawal P, Chawla R, Yang D, Hurley L. (2017) Insight into the Complexity of the i-Motif and G-Quadruplex DNA Structures Formed in the KRAS Promoter and Subsequent Drug-Induced Gene Repression. J. Am. Chem. Soc., 28;139(25):8522-8536, DOI: 10.1021/jacs.6b10028, PMID: 28570076. PMCID: PMC5978000.

Xiao L, Ishizuka I, Hong-Liang b, Wada, K, Takada, Y, Iida, K, Nagasawa K, Yang D, Xu, Y. (2017) Structure-dependent binding of hnRNP A1 to telomere RNA. J. Am. Chem. Soc., 139(22):7533-7539, DOI: 10.1021/jacs.7b01599, PMID: 28510424. PMCID: PMC5977995.

Brown RV, Wang T, Chappeta VR, Wu G, Onel B, Chawla R, Quijada H, Camp SM, Chiang ET, Lassiter OR, Lee C, Phanse S, Megan A, Zhou TP, Garcia JGN, Gokhale V, Yang D, Hurley L. (2017) The Consequences of Overlapping Gâ��Quadruplexes and iâ��Motifs in the Platelet-Derived Growth Factor Receptor β Core Promoter Nuclease Hypersensitive Element Can Explain the Unexpected Effects of Mutations and Provide Opportunities for Selective Targeting of Both Structures by Small Molecules To Downregulate Gene Expression. J. Am. Chem. Soc., 7;139(22):7456-7475, DOI: 10.1021/jacs.6b10028, PMID: 28471683. PMCID: PMC5977998.

Wang KB, Li DH, Bao Y, Cao F, Wang WJ, Lin C, Bin W, Bai J, Pei YH, Jing YK, Yang D, Li ZL, Hua HM. (2017) Structurally Diverse Alkaloids from the Seeds of Peganum harmala. J. Nat. Prod., 80(2):551-559, DOI: 10.1021/acs.jnatprod.6b01146, PMID: 28128938. PMCID:PMC5518681.

Lin C. and Yang Y. (2017) Human Telomeric G-Quadruplex Structures and G-Quadruplex-Interactive Compounds. Telomeres and Telomerase: Methods Mol Biol, 735:77-96, DOI: 10.1007/978-1-4939-6892-3_17.

Mo H, Harwood JS, Yang D, Post CB. (2017) A simple method for NMR t1 noise suppression. Journal of Magnetic Resonance, Volume 276, pp 43-50, DOI: 10.1016/j.jmr.2016.12.014.

Buket Onel, Megan Carver, Guanhui Wu, Daraia Timonina, Salil Kalarn, Marti Larriva, Danzhou Yang “A new G-quadruplex with hairpin loop immediately upstream of the human BCL-2 P1 promoter modulates transcription” J. Am. Chem. Soc., 138 (8), 2563–2570, 2016.

Clement Lin, Danzhou Yang, “DNA Recognition by a DNA Bis-intercalating Anticancer Drug XR5944”, Current Topics in Medicinal Chemistry, 15, 1385-1397, 2015.

Lihua Zhang, Hua Liu, Yong Shao, Clement Lin, Huan Jia, Gang Chen, Danzhou Yang, and Ying Wang. “Selective Lighting Up of Epiberberine Alkaloid Fluorescence by Fluorophore-Switching  Aptamer and Stoichiometric Targeting of Human Telomeric DNA Gâ��Quadruplex Multimer” Analytical Chemistry, 87, 730737, 2015.

Prashansa Agrawal, Clement Lin, Raveendra I. Mathad, Megan Carver, and Danzhou Yang “The Major G-Quadruplex Formed in the Human BCL-2 Proximal Promoter Adopts a Parallel Structure with a 13-nt Loop in K+ Solution” J. Am. Chem. Soc., 136 (5), 1750–1753, 2014.

Clement Lin, Raveendra I. Mathad, Zhenjiang Zhang, Neil Sidell, Danzhou Yang, “Molecular Recognition of TFF1 Estrogen Response Element by a DNA Bis-intercalating Anticancer Drug XR5944”, Nucleic Acid Research, 42 (9), 6012-6024, 2014.

Samantha Kendrick, Hyun-Jin Kang, Mohammad Alam, Manikandadas Madathil, Prashansa Agrawal, Vijay Gokhale, Danzhou Yang, Sidney M. Hecht, and Laurence H HurleyThe Dynamic Character of the BCL2 Promoter i-Motif Provides a Mechanism for Modulation of Gene Expression by Compounds That Bind Selectively to the Alternative DNA Hairpin Structure” J. Am. Chem. Soc., 136, 4161-4171, 2014.

Prashansha Agrawal, Emmanuel Hatzakis, Kexiao Guo, Megan Carver, Danzhou Yang, “Solution structure of the major G-quadruplex formed in the human VEGF promoter: Insights into loop interactions of the parallel G-quadruplexes” Nucleic Acid Research, 41(22), 10584-10592, 2013.

Christine Kaiser, Vijay Gokhale, Danzhou Yang, Laurence Hurley  “Gaining Insights into the Small Molecule Targeting of the G-Quadruplex in the c-MYC Promoter Using NMR and an Allele-Specific Transcriptional Assay”, Topics in Current Chemistry:Quadruplex Nucleic Acids, Volume 330, 1-21, 2013.

Yuwei Chen, Prashansa Agrawal, Robert V. Brown, Emmanuel Hatzakis, Laurence Hurley, Danzhou Yang “The Major G-Quadruplex Formed in the Human Platelet-Derived Growth Factor Receptor b (PDGFR-b) Promoter Adopts a Novel Broken-Strand Primarily Parallel Structure”, J. Am. Chem. Soc. 134 (32), 13220–13223, PMID:22866911. 2012.

Yuwei Chen, and Danzhou Yang “Sequence, Stability, Structure of G-Quadruplexes and Their Drug Interactions”, Current Protocols in Nucleic Acid Chemistry, 50:17.5.1–17.5.17. 2012

Jixun Dai, Megan Carver, Laurence H. Hurley, Danzhou Yang “Solution structure of a 2:1 quindoline–c-MYC G-quadruplex.  Drug-induced reorientation of the flanking sequence and implications for drug design”, J Am Chem Soc, 133 (44), 17673–17680, 2011

Neil Sidell, Raveendra I. Mathad, Feng-jue Shu, Zhenjiang Zhang, Caleb B. Kallen, Danzhou Yang “Intercalation of XR5944 with the estrogen response element is modulated by the tri-nucleotide spacer sequence between half-sites.” Journal of Steroid Biochemistry and Molecular Biology, 124: 121-127, 2011.

Raveendra I. Mathad, Emmanuel Hatzakis, Jixun Dai, and Danzhou Yang “c-Myc promoter G-quadruplex formed at the 5’-end of NHE III1 element: insights into biological relevance and parallel-stranded G-quadruplex stability” Nucleic Acid Research, 39(20): 9023-9033, 2011

Danzhou Yang and Keika Okamoto “Structural Insights Into G-Quadruplexes: Towards New Anti-Cancer Drugs.” Future Medicinal Chemistry, Vol. 2, No. 4, 619-646, April 2010.

Jixun Dai, Attila Ambrus, Laurence H. Hurley, Danzhou Yang. “A direct and nondestructive approach to determine the folding structure of the I-motif DNA secondary structure by NMR.” J Am Chem Soc 131(17): 6102-4, 2009.

Chandanamalie Punchihewa, Megan Carver, Danzhou Yang. “DNA sequence selectivity of human topoisomerase I-mediated DNA cleavage induced by camptothecin.” Protein Sci. 18(6): 1326-31, 2009.

Jixun Dai, Megan Carver, Danzhou Yang “Polymorphism of human telomeric G-quadruplex structures” Biochimie 90, 1172-1183, 2008.

Jixun Dai, Megan Carver, Chandanamalie Punchihewa, Roger A. Jones, and Danzhou Yang “Structure of the hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: Insights into structure polymorphism of the human telomeric sequence.” Nucleic Acid Research, 35, 4927-4940, 2007. (cover article)

Paula Bates, Jean-Louis Mergny and Danzhou Yang, “Quartets in G-major. The First International Meeting on Quadruplex DNA” EMBO report, 8, 1003-1010, 2007.

Chandanamalie Punchihewa, Adrian De Alba, Neil Sidell, Danzhou Yang “XR5944, a potent inhibitor of estrogen receptors”, Molecular Cancer Therapeutics 6, 213-219, 2007. (featured in DailyUpdates/LeadDiscovery Headline Articles.)

Jixun Dai, Thomas S. Dexheimer, Ding Chen, Megan Carver, Attila Ambrus, Roger A. Jones, Danzhou Yang “An Intramolecular G-Quadruplex Structure with Mixed Parallel/Antiparallel G-strands Formed in the Human BCL-2 Promoter Region in Solution.” J. of American Chemical Society 128, 1096 –1098, 2006.

Attila Ambrus, Ding Chen, Jixun Dai, Tiffanie Bialis, Roger A. Jones, Danzhou Yang “Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution.” Nucleic Acid Research 34(9), 2723-2735, 2006. (featured in C&EN, issue of July 31, 2006.)

Laurence H. Hurley, Daniel D. Von Hoff, Adam Siddiqui-Jain, and Danzhou Yang “Drug Targeting of the c-MYC Promoter to Repress Gene Expression via a G-Quadruplex Silencer Element” Seminars in Oncology, 33(4), 498-512, 2006.

Attila Ambrus, Ding Chen, Jixun Dai, Roger A. Jones, Danzhou Yang “Solution Structure of the Biologically Relevant G-Quadruplex Element in the Human c-MYC Promoter. Implications for G-Quadruplex Stabilization.”  Biochemistry, 44, 2048-2058, 2005.