Danzhou Yang

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

Research in my laboratory is focused on structures and functions of cancer-specific DNA molecular targets and structure-based rational drug design. Particularly, we work on G-quadruplex (G4) DNA secondary structures formed in human oncogene promoters and human telomeres, which are attractive new molecular targets for cancer therapeutics. We seek to understand structure-function relationships of DNA G-quadruplexes, their protein interactions and drug targeting. In addition, we work on DNA-targeted anticancer drugs that inhibit transcription factors and topoisomerases. We use a combination of structural, biophysical, biochemical, molecular, and cellular methods in our research, in particular high-field NMR spectroscopy for biomolecular structural study.

Selected Publications:

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.

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. 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.

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.

Press release: https://www.purdue.edu/newsroom/releases/2019/Q3/new-anticancer-agents-have-potential-to-better-control-tumor-growth-in-nearly-every-cancer-type.html; Science Daily, https://www.sciencedaily.com/releases/2019/07/190708172436.htm

Yang D. (2019) G-Quadruplex DNA and RNA, Methods Mol Biol. 2035:1-24. PMID:31444741.

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.

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

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.

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. Analytical Chemistry 7;89(21):11846-11852.

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.

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.

Onel B, Carver M, Wu G, Timonina D, Kalarn S, Larriva M, Yang D. (2016) A new G-quadruplex with hairpin loop immediately upstream of the human BCL-2 P1 promoter modulates transcription. J. Am. Chem. Soc., 138 (8), pp 2563–2570. See our current publications at  https://www.ncbi.nlm.nih.gov/myncbi/danzhou.yang.1/bibliography/public/

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., 2016, 138 (8), pp 2563–2570.

Clement Lin, Danzhou Yang, “DNA Recognition by a DNA Bis-intercalating Anticancer Drug XR5944”, Current Topics in Medicinal Chemistry: Potential Therapeutic Agents based on DNA/RNA Sequence-selective Binding Compounds. 2015.

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-ß (PDGFR-ß) Promoter Adopts a Novel Broken-Strand Primarily Parallel Structure”, J. Am. Chem. Soc. 134 (32), 13220–13223, PMID:22866911. 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

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, 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)

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.

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.