Dr. Philip Yangyuoru
Office Hours: :
MW 10 am and 11 am and F 3 pm. All other office hours by appointment.
Research Interest :
Bioanalytical chemistry, chemical separations, forensic biochemistry, and biosensors.
▪ Develop high-throughput methods for probing noncanonical nucleic acid secondary structures especially G-quadruplexes (Fig. a) and i-motifs (Fig. c).
▪ Design nucleic acid-based biosensors for biomarkers, environmental impact, and how nucleic acid structures are modulated by drug molecules (Fig. b) and proteins (Fig. c).
▪ Enzyme kinetics and the mechanisms by which helicase proteins manipulate nucleic acid secondary structures.
Nucleic acid sequences fold into diverse unique secondary structure conformations under different conditions. Single-stranded DNA (ssDNA) regions consisting of at least four closely spaced runs of three or more consecutive guanines or cytosines strongly tend to fold into stable G-quadruplex (G4) or i-motif structures respectively. The stability of these structures makes them suitable scaffolds for designing biosensors. Moreover, these unique structures have been implicated in regulating many important biological processes.
1. Chang-Gu B, Bradburn D, Yangyuoru PM, Russell R, “The DHX36-specific-motif (DSM) enhances specificity by accelerating recruitment of DNA G-quadruplex structures” Journal of Biol. Chem. 2020; doi.10.1515/hsz-2020-0302.
2. Yangyuoru PM, Bradburn D, Liu Z, Xiao TS, Russell R “The G-quadruplex (G4) resolvase DHX36 efficiently and specifically disrupts DNA G4s via a translocation-based helicase mechanism.” Journal of Biol. Chem. 2017; DOI: 10.1074/jbc.M117.815076.
3. Yangyuoru PM, Di Antonio M, Ghimire C, Biffi G, Balasubramanian S, Mao H, “Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex” Angew. Chem. Int. Ed. 2014; DOI: 10.1002/anie.201408113.
4. Yangyuoru PM, Zhang AYQ, Zhe S, Koirala D, Balasubramanian, S Mao H, “Mechanochemical Properties of Individual Human Telomeric RNA G-quadruplexes” ChemBioChem. 2013; DOI: 10.1002/cbic.201300350.
5. Yangyuoru PM, Dhakal S, Yu Z, Koirala D, Mwongela SM, Mao H. “Single-Molecule Measurements of the Binding between Small Molecules and DNA Aptamers.” Anal Chem. 2012; doi: 10.1021/ac300427d.
6. Yangyuoru PM, Otieno AC, Mwongela SM. “Determination of Sphingosine Kinase 2 Activity using Fluorescent Sphingosine by Capillary Electrophoresis.” Electrophoresis. 2011; doi: 10.1002/elps.201000495.
7. Yangyuoru PM, Webb JW, Shaw CF III. “Proton-Linked bi- and tri-Metallic Gold Cyanide Complexes observed by ESI-MS Spectrometry.” J. Inorg. Biochem.2008; doi: 10.1016/j.jinorgbio.2007.10.020.
8. Yangyuoru PM, Webb JW, Shaw CF III. “Glutathionato-S-Gold(III) Complexes formed as Intermediates in the Reduction of Auricyanide by Glutathione.” J. Inorg. Biochem. 2008; doi: 10.1016/j.jinorgbio.2007.10.028.
9. Cui Y, Koirala D, Kang H-J, Dhakal S, Yangyuoru PM, Hurley LH, Mao H. “Molecular Population Dynamics of DNA Structures in a Bcl-2 Promoter Sequence is Regulated by Small Molecules and the Transcription factor hnRNP LL” Nucleic Acids Res. 2014; doi:
10.1093/nar/gku185. 10. Punnoose JA, Cui Y, Koirala D, Yangyuoru PM, Ghimire C, Shrestha P, Mao H. “Interaction of G-quadruplexes in the Full-length 3' Human Telomeric Overhang”, JACS, 2014, 18062-18069. DOI 10.1021/ja510079u.
11. Ghimire C, Park S, Iida K, Yangyuoru PM, Otomo H, Yu Z, Nagasawa K, Sugiyama H, and Mao H, “Direct Quantification of Loop Interaction and π-π Stacking for G-quadruplex Stability at the Submolecular Level”, JACS, 2014, dx.doi.org/10.1021/ja503585h.
12. Dhakal S, Cui Y, Koirala D, Ghimire C, Kushwaha S, Yu Z, Yangyuoru PM, Mao H. “Structural and Mechanical Properties of Individual Human Telomeric G-quadruplexes in Molecularly Crowded Solutions” Nucleic Acids Res. 2013; doi: 10.1093/nar/gkt038.
13. Koirala D, Yangyuoru PM, Mao H. “Mechanical Affinity as a New Metrics to Evaluate Binding Events” Rev. Anal. Chem. 2013: Invited Review. DOI 10.1515/revac-2013-0004.