Research in my laboratory centers around bioorganic chemistry of nucleic acids. We aim to develop methodologies for the synthesis of natural and modified nucleic acids, and characterization of the structures and properties of these molecules. Four research themes are currently under investigation.

1. Synthesis of modified oligonucleotides.

We are interested in developing chemistry for the synthesis and incorporation of modified nucleosides into oligonucleotides. These modified nucleic acids are labeled with stable isotopes as NMR probes, fluorophores for fluorescent investigation, or photoisomerizable or crosslinking moieties that allow for the control of nucleic acid structures and functions.

2. Nucleic acid handedness.

We are interested in studying the structure and potential biological relevance of left-handed nucleic acids, especially Z-DNA. Work in this area involves chemical syntheses of modified nucleosides and incorporation of these nucleosides into oligonucleotides to modulate and probe the handedness transition.

3. Nucleic acid structural plasticity.

We have developed a suite of analytical chemistry tools to study the structural polymorphism of nucleic acids. Using denaturing and non-denaturing HPLC, circular dichroism, UV/vis, NMR, FRET, Raman, and microfluidic devices, we investigate the conformational flexibility of relatively short nucleic acids, such as trinucleotide repeat sequences, while probing the conformational rigidity of long nucleic acids. We are also studying the impact of molecular crowding on the structures and functions of nucleic acids, both in cytoplasmic fluids and simulated fluids.

4. Chemical epigenetics.

We are developing approaches to study the molecular machinery involved in epigenetic regulations, especially with DNA methylation. In this respect, work is ongoing to investigate conformational changes that may accompany epigenetic modifications of DNA.

Publications (*corresponding author)

Independent publications

1. A prototype microfluidic device to simulate water flow patterns in Lake Ontario, 2024, manuscript under revision.
2. Precipitation of oligonucleotides for mass spectrometric analysis, 2024, under review
3. A positive correlation between the pseudorotational phase angle P and the _H torsion angle (H4’-C4’-C3’-H3’) in nucleosides and nucleic acids, 2024, under review
4. Far UV Synchrotron Radiation Circular Dichroism of Nucleosides, 2024, under review
5. El-Morched, M.; Barroco, C.; Simionescu, R.; Harroun, T.; Yan, H.* Characterization of simulated cytoplasmic fluids, ChemistrySelect 2024, 9, e202402861.
6. Betancourt, K.; Sultana, R.; Petrovic, D.; Gilmour, Q.; Ebralidze,I. E.; Zenkina, O. E.*; Yan, H.* Preparation and surface characterization of DNA encapsulated by silica nanoparticles, Nanopart. Res. 2024, 26, 176.
7. Preparation and surface characterization of DNA encapsulated by silica nanoparticles
8. Li, Q.; Sanghvi, Y. S.;* Yan, H.*An expanded framework toward improving the detritylation reaction in solid-phase oligonucleotide syntheses – Filling the gap, Nucleosides Nucleotides Nucleic Acids 2024, 1–9. https://doi.org/10.1080/15257770.2024.2388789
9. Li, Q.; Sanghvi, Y. S.; Yan, H.* DFA as an alternative acid in the detritylation reaction, Nucleosides Nucleotides Nucleic Acids 2024, 11:1-9. https://doi.org/1080/15257770.2024.2337145
10. Li, Q.; Yan, H.* “Difficult” deoxyribonucleotide sequences in the solid-phase synthesis by the phosphoramidite chemistry, Nucleosides Nucleotides Nucleic Acids 2023, 655-663.
11. Bennett, H.; Li, Y.;* Yan, H.* Conformational flexibility and adaptive recognition of aptamers – a mini review. Aptamers, 2023, 7, 1-6.
12. Vanloon, J.; Bennett, H.; Martin, A.; Wien, F.;* Harroun, T.*; Yan, H.* Synchrotron radiation circular dichroism spectroscopy of DNA at millimolar concentrations. Med. Chem. Lett. 2023, 129376.
13. Andress, C.; Kappel, K.; Cuperlovic-Culf, M.; Yan, H.; Li, Y.* DAPTEV: Deep Aptamer Evolutionary Modelling for COVID-19 Drug Design. PLOS Comput. Biol. 2023, 19, e1010774.
14. Zou, W.;* McAdorey, A.; Yan, H.; Chen, W.* Nanomedicine to overcome antimicrobial resistance: challenges and prospects. Nanomedicines 2023, 18,
15. Joshi, D. K.; Betancourt, F.; Pilkington, M.; Yan, H.* Neutral BODIPY photosensitizers. Photochem. Photobiol. A: Chem. 2023, 114770.
16. Bennett, H-A; Li, Y;* Yan, H.* Thermal treatment affects aptamers’ structural profiles. Med. Chem. Lett. 2023, 82,129150.
17. Joshi, D. K.; Betancourt, F.; McAdorey, A.; Yalagala, R. S.; Poupon, A.; Yan, H.* BODIPY quaternary ammonium salt as photosensitizers, Photochem. Photobiol. A: Chem. 2023, 434, 114213.
18. Bennett, H.; McAdorey, A.; Yan, H.* Staining properties of selected commercial fluorescent dyes toward B- and Z-DNA. Fluoresc. 2023, doi.org/10.1007/s10895-023-03343-8.
19. Wang, G.; Xu, J.; Traynor, S. M.; Wu, X.; Chen, H.; Eljabu, F.; Yan, H.; Li, F.* Weighing the thermodynamics and kinetics of chemically modified DNA using a rationally designed DNA balance, Am. Chem. Soc. 2021, 143, 13655.
20. Yan, H.;* Chen, W.* The promise and challenges of cyclic dinucleotides as

molecular adjuvants for vaccine development, Vaccines 2021, 9, 917. (invited review)

21. McAdorey, A.; Bennett, H.; Vanloon, J.; Yan, H.* Use of anion-exchange (AEX) HPLC to study nucleic acid polymorphism, Chromatogr. B 2021, 1180, 122890.
22. Betancourt, F.; Valente, A.; Yan, H.* 1,8-Naphthalimide derivatives as probes for protein surface hydrophobicity. Photochem. Photobiol. A: Chem. 2021, 418, 113386.
23. Vanloon, J.; Harroun, T.;* Yan, H.* Circular dichroism spectroscopy of DNA duplexes at near-biological concentrations. Med. Chem. Lett. 2021, 43, 128053.
24. Betancourt, F.; Helmkay, J.; Yan, H.* Microwave-assisted synthesis and fluorescent properties of 4-phenyl-1,8-naphthalimide. Molbank 2020, M1127.
25. Solodinin, A.; Ollivier, S.; Helmkay, J.; Yan, H.* N-2-Isobutyryl-8-fluoro-2’-deoxyguanosine: synthesis and reactivity. Molbank 2020,
26. Sun, J.; Joshi, D.; Betancourt, F.; Solodinin, A.; Woodland, B.; Yan, H* Anion exchange chromatography of oligonucleotides under denaturing conditions. Nucleosides, Nucleotides and Nucleic acids. 2020, 1-11.
27. Huang, C. Y.; Yan, H.; Chiou, Y.-R.; Wan, C.-F.; Wu, A.-T.* A Schiff-based fluorescence sensor for the detection of Cu²⁺ and its application in living cells. Photochem. Photobiol. A: Chem. 2020, 390, 112326.
28. Li, J.; Kuo Lee, R.; Chen, W.; Yan, H.* 2’-Fluoro-c-di-GMP as an oral vaccine adjuvant.RSC Advances 2019, 9,
29. Solodinin, A.; Gautrais, A.; Yan, H.* Incorporation of 5-fluoro-2’-deoxycytidine into oligonucleotides for the study of DNA structures by ¹⁹F NMR spectroscopy. ACS Omega 2019, 4, 19716 (invited).
30. Sun, J.; Vanloon, J.; Yan, H.* Influence of low-power microwave irradiation on DNA hybridization and polymerase reactions. Tetrahedron Lett. 2019, 60, 151060.
31. Mazinani, S. M.; Noaman, N.; Pergande, M. R.; Cologna, S. M.; Coorssen, J.;* Yan, H.* Exposure to microwave irradiation at constant culture temperature slows the growth of Escherichia coli DE3 cells, leading to modified metabolic profiles. RSC Advances 2019, 9, 11810.
32. Bordeleau, E.; Mazinani, S. A.; Nguyen, D.; Betancourt, F.; Yan, H.* Abrasive treatment of microtiter plates improves the reproducibility of bacterial biofilm assays – preliminary study of the roles of flavonoids in biofilm formation in subtilis. RSC Advances 2018, 8, 32434.
33. Mazinani, S. A.; Stuart, J. A.; Yan, H.* Microwave-assisted delivery of an anticancer drug to cancer cells. RSC Advances 2018, 8, 31465.
34. Jun, M.; Joshi, D. J.; Yalagala, R.; Vanloon, J.; Lough, A. J.; Gordon, H. L.; Yan H.* Spectroscopic characterization of cyclic azobenzene analogues and confirmation of the structure of trans-cyclic azobenzene by X-ray crystallography, ChemistrySelect 2018, 3, 2697.
35. Joshi, D. J.; Jun, M.; Yang, L.; Lough, A. J.;* Yan H.* Further investigation on the nitration of BODIPY with cupric nitrate, Acta Crystallogr. E. 2018, E74, 103.
36. Sie, Y.-W.; Li, C.-L.; Wan, C.-F.; Yan, H.; Wu, A.-T.* A novel colorimetric probe for dual sensing of Hg²⁺ and Cu²⁺ ions in water. Photochem. Photobiol. A: Chem. 2018, 353, 19.
37. Sie, Y.-W.; Li, C.-L.; Wan, C.-F.; Chen, J.-H.; Hu, C.-H.; Yan, H.; Wu, A.-T.* A colorimetric probe for dual sensing of Hg²⁺ and Cu²⁺ ions in water, Chim. Acta 2017, 467, 325.
38. Mazinani, S. A.; Moradi, F.; Stuart, J. A.; Yan, H.* Microwave Irradiation of PC3 Cells at Constant Culture Temperature Alters the Incorporation of BODIPY into Cells and the Reduction of MTT, ChemistrySelect, 2017, 2, 7983.
39. Yang, L.; Drew, B.; Yalagala, R.; Chaviwala, R.; Simionescu, R.; Lough, A.;* Yan, H.* Solvent-dependent behaviours of 3-amino-1,6-diethyl-4,4-diphenyl-2,5,7-trimethyl-1,5,7,8-tetramethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene, Acta Crystallogr. E. 2017, E73, 378.
40. Yan, H.;* Powers, R.; Gibbons, A.; Joshi, D. (2017) Z-DNA: Chemistry and Biological Relevance. In: Reedijk, J. (Ed.) Elsevier Reference Module in Chemistry, Molecular Sciences and Chemical Engineering. Waltham, MA: Elsevier. 20-Mar-17 doi: 10.1016/B978-0-12-409547-2.12656-3 (invited).
41. Yang, L.; Liao, D.-J.; Wu, A.-W.;* Yan, H.* Synthesis and fluorescent properties of aza-crown ether tethered BODIPY fluorophores, Tetrahedron Lett. 2017, 58, 889.
42. Qiu, H.; Li, Z.; KuoLee, R.; Harris, G.; Gao, X.; Yan, H.; Xu, H.; Chen, W.* Host resistance to intranasal Acinetobacter baumannii reinfection in mice, Dis. 2016, 74, pii: ftw048. doi: 10.1093/femspd/ftw048.
43. Mazinani, S. A.; Yan, H.* Impact of microwave irradiation on enzymatic activity at constant bulk temperature is enzyme-dependent, Tetrahedron Lett. 2016, 57, 1589.
44. Yalagala, R.; Mazinani, S. A.; Maddalena, L. A.; Stuart, J. A.; Yan, F.; Yan, H.* Microwave assisted synthesis of BODIPY-sugar conjugates through the Click chemistry and assembly of the conjugate into bilayers. Carbohydrate Res. 2016, 424, 15.
45. Eljabu, F.; Dhruval, J.; Yan, H.* Incorporation of cyclic azobenzene into oligodeoxynucleotides for the photo-regulation of DNA hybridization. Med. Chem. Lett. 2015, 25, 5594.
46. Mazinani, S. A.; DeLong B.; Yan, H.* Microwave radiation accelerates trypsin-catalyzed peptide hydrolysis. Tetrahedron Lett. 2015, 56, 5804.
47. Yan, H.;* Yalagala, R.; Yan, F. Fluorescently labelled glycans and their applications, J. 2015, 32, 559.
48. Kuolee, R.; Harris, G.; Yan, H.; Xu, H. H.; Conlan, W. J.; Patel, G. B.; Chen, W.* Intranasal immunization protects against Acinetobacter baumannii-associated pneumonia in mice, Vaccine 2015, 33, 260.
49. Bordeleau, E.; Oberc, C.; Ameen, E.; Mendes da Silva, A.; Yan, H.* Identification of cytidine 2’,3’-cyclic monophosphate and uridine 2’,3’-cyclic monophosphate in Pseudomonas fluorescens pfo-1 culture. Med. Chem. Lett. 2014, 24, 4520.
50. Yang, L.; Yalagala, R. S.; Hutton, S.; Lough, A. J.; Yan, H.* Reactions of BODIPY with nitrates, Synlett 2014, 25, 2661.
51. Yalagala, R. S.; Yan, H.* Reactions of alkynes with trisubstituted (Z)-bromoalkenyl-pinacolboronates towards the synthesis of 1,2,4,6-tetrasubstituted benzenes. Tetrahedron Lett. 2014, 55, 4830.
52. Yalagala, R. S.; Zhou, N.; Yan, H.* Palladium(II)–copper(I) mediated homotrimerization and homotetramerization of terminal alkynes, Tetrahedron Lett. 2014, 55, 1883.
53. Yang, L.; Li, J.; Simionescu, R.; Yan, H*. Observation of two N₂-isobutyrylguanine tautomers by NMR spectroscopy, Reson. Chem. 2013, 51, 60–64.
54. Dhruval, J.; Mitchell, M.; Bruce, D.; Lough, A.; Yan, H.* Synthesis of cyclic azobenzene analogues, Tetrahedron, 2012, 68, 8670.
55. Zhou, N.; Wang, Q.; Lough, A.; Yan, H.* Preparation of (Z)-1,2-dichloroalkenes from terminal alkynes, J. Chem. 2012, 90, 625.
56. Yang, L.; Yan, H.* A Mannich-type reaction at the meso-methyl position of the BODIPY fluorophore, Synlett.2012, 23, 1526.
57. Cheng, H-J; Yan, H.; Sun, Y-L; Lu, C-Y; Huang, T-Y; Chen, S-J; Hu, C-H; Wu, Y-Y; Wu, A-T.* A simple and highly selective receptor for iodide in aqueous solution, Analyst 2012, 137, 571.
58. Yang, L.; Simionescu, R.; Lough, A.; Yan, H.* Some observations relating to the stability of the BODIPY fluorophore under acidic and basic conditions, Dyes Pigments 2011, 91, 264.
59. Zhao L, KuoLee R, Harris G, Tram K, Yan H, Chen W.* c-di-GMP protects against intranasal Acinetobacter baumannii infection in mice by chemokine induction and enhanced neutrophil recruitment, Immunopharmacol. 2011, 11, 1378.
60. Tram, K.; Sangvi, Y.; Yan, H.* Further studies on the detritylation in solid phase oligodeoxyribonucleotide synthesis, Nucleoside, Nucleotides & Nucleic Acids. 2011, 30, 12.
61. Tram, K.; Twohig, D.; Yan, H.* Oligonucleotide labeling using BODIPY phosphoramidite, Nucleoside, Nucleotides & Nucleic Acids. 2011, 30, 1.
62. Chen, W.*; Patel, G.; Yan, H. Zhang, J. Recent advances in the development of novel mucosal adjuvants and antigen delivery systems, Human Vaccines, 2010, 6, 683.
63. Yan, H.*; Chen, W. 3’,5’-Diguanylic acid-a small nucleotide that makes big impact, Soc. Rev. 2010, 39, 2914.
64. KuoLee, R.; Yan, H.; Chen, W.* cdiGMP as a mucosal vaccines adjuvant. Vaccine, 2010, 28, 3080.
65. Zhao, Y.; Tram, K.; Yan, H.* Synthesis and characterization of mannosylated oligoribonucleotides, Carbohydrate Res. 2009, 344, 2137.
66. Yan, H.;* KuoLee, R.; Tram, K.; Qiu, H.; Zhang, J.; Patel, G.B.; Chen, W.^* Intranasal immunization of mice with bacterial second messenger cdiGMP elicits protective immunity against nasopharyngeal carriage of Streptococcus pneumoniae, Biophys. Res. Commun. 2009, 387, 581.
67. Tram, K.; Yan, H.;* Jenkins, H.; Vassiliev, S.; Bruce, D. The synthesis and crystal structure of unsubstituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY), Dyes Pigm. 2009, 82, 392.
68. Tram, K.; McIntosh, W.; Yan, H*. Synthesis of glycosyl dipyrromethanes, Tetrahedron Lett. 2009, 50, 2278.
69. Yan, H.;* Wang, X.; Kuolee, R.; Chen, W. Synthesis and immunostimulatory properties of the phosphorothioate analogues of cdiGMP, Med. Chem. Lett. 2008, 18, 5631.
70. Tram, K.; Wang, X.; Yan, H.* Facile synthesis of oligonucleotide phosphoroselenoates, Lett. 2007, 9, 5103.
71. Yan, H.;* Anguilar, A. L.; Zhao, Y. Preparation of carbohydrate–oligonucleotide conjugates using the squarate spacer, Med. Chem. Lett. 2007, 17, 6535.
72. Yan, H.;* Anguilar, A. L. Synthesis of 3’,5’-cyclic diguanylic acid (cdiGMP), Nucleoside, Nucleotides & Nucleic Acids 2007, 26, 189.
73. Yan, H.;* Tram, K. Glycotargeting to improve cellular delivery efficiency of nucleic acids, J. 2007, 24, 107.

 

Other independent publications

74. Yan, H.; Chen, W.; KuoLee, R. United States Patent No. 10,092,644, October 9, 2018.
75. Yan, H.; Chen, W.; KuoLee, R. WO Patent No. 2015/074145A1, May 28, 2015.
76. Yan, H.; Tram, K. Compounds for fluorescent labelling. United States Patent No. 8,519,153. Issued on August 27,2013.
77. Tram, K.; Jenkins, H. A.; Yan, H.* (2010) Private communication to the Cambridge Structural Database, deposition number CCDC 793318.
78. Millar, S; Yan, H.; Sanghvi, Y. S.; Pon, R. Some observations on detritylation in solid-phase oligonucleotide synthesis. Nucleic Acids Symp. Ser. 2008, 52, 311.
79. Zhao, Y.; Yan, H. Preparation of Mannosylated Oligoribonucleotides, Nucleic Acids Symp. Ser. 2008, 52, 89.
80. Yan, H.; Humes, E. Convenient synthesis of 3’,5’-cyclic diguanylic acid (cdiGMP), Nucleic Acids Symp. Ser.2006, 50, 5.

 

Post-doctoral and graduate publications

81. Yan, H.; Jennings, H. J. Synthesis of mono- and di-sialophospholipids via the H-phosphonate approach, J. Chem. 2006, 84, 540.
82. Reese, C. B.; Yan, H. Alternatives to the 4,4′-dimethoxytrityl (DMTr) protecting group, Tetrahedron Lett. 2004,45, 2567–2570.
83. Reese, C. B.; Yan, H. Further studies with adenosine 5′-dithiophosphoromorpholidate. A convenient preparation of nucleoside phosphorodithioates by a triester approach, Tetrahedron Lett. 2004, 45, 2653.
84. Reese, C. B.; Yan, H. An approach to the desulfurization of oligonucleotide phosphorothioates, Tetrahedron Lett.2003, 44, 2501.
85. Reese, C. B.; Yan, H. Solution phase synthesis of ISIS 2922 (Vitravene) by the modified H-phosphonate approach. Chem. Soc., Perkin. Trans. 1 2002, 23, 2619.
86. Reese, C. B.; Yan, H. Xanthen-9-ylidene protecting groups in glycerol chemistry. Chem. Soc., Perkin Trans. 12001, 15, 1807.
87. Reese, C. B.; Yan, H. Reaction between pyrrole and orthoesters: preparation of tri-(pyrrole-2-yl)alkanes. Tetrahedron Lett. 2001, 42, 5545.
88. Reese, C. B.; Song, Q.; Yan, H. Xanthen-9-ylidene and 2,7-dimethylxanthen-9-ylidene protecting groups. Tetrahedron Lett. 2001, 42, 1789.

CHEM 1P00: Introductory Chemistry

CHEM/BTEC 5P28/4P28: Bioorganic chemistry – carbohydrates and nucleic acids

CHEM/BTEC 3P93: Protein and nucleic acid chemistry

CHEM/BTEC 4P26: Toxicological chemistry and biochemistry

Current members:

Frank Betancourt (PhD student)

Jesse Vanloon (PhD student)

Alyssa McAdorey (PhD student)

Mariam El-Morched (PhD student)

Raissa Sultana (MSc student)

Nicole Brauch (MSc student)

Quanjian Li (MSc student)

Matteo Iacucci (MSc student)

Donya Shahmoradi (MSc student)

Fiatan Hague (MSc student)

Hamza Qureshi (MSc student)

Stephanie Bedard (Honours thesis)

Jerome Siju Thomas (Honours thesis)

Giovanna Costa (Exchange student)

 

Past members:

PDF

Kha Tram (2016-2017)

Ningzhang Zhou (2011-2012)

Qiang Wang (2011)

Nasser Ali (2009)

 

PhD

Meesook Jun

Ravi Yalagala (2012-2016)

 

MSc

Khatma Milah (2016-2018)

Emily Bordeleau (2014-2017)

Christopher Oberc (2012-2015)

Fatma Eljabu (2013-2015)

Nazanin Heidari (2013-2015)

Dhruval Joshi (2011-2013)

Viola Yang (2010-2013)

Yuyan Zhao (2009-2011)

Kha Tram (2009-2011)

Jia Li (2009-2012)

 

BSc Honours

Mohamed Mahrouse (2018)

Kaitie Kean (2017-2018)

Courtney Farno (2017-2018)

Heather Hendrik (2017-2018)

Harris Sheihk (2017-2018)

Ashley Gibbons (2016-2017)

Eve Ameen (2016-2017)

Frank Betancourt (2016-2017)

Rhys Power (2016-2017)

David Nguyen (2015-2016)

Anastasia Burdilov (2015)

Matt Bell (2014-2015)

Ben DeLong (2013-2014)

Emily Bordeleau (2013-2014)

Scott Henderson (2013-2014)

Jassey Gosal (2013-2014)

Sukhmani Gill (2013-2014)

Brett Drew (2012-2013)

Rameez Chaviwala (2012-2013)

Matt Mitchell (2010-2011)

Ken Ellens (co-supervised)

Kha Tram (2008-2009)

Shannon Millar (2008-2009)

Aime Aguilar Lopez (2005-2007)

 

Co-op

Michelle Giroux

Jagandeep Saraya

 

Summer and CHEM 2/3P98

Frank Lu (USRA summer student, 2011 and 2012)

Hany Ibrahim (CHEM 3P98)

Daniel Twohig (undergraduate research assistant, 2009)

 

High school mentorship

Stephanie Hutton (2013)

Westen McIntosh (2009)

 

Internship

Angeline Gautrais (Rennes, 2018)

Karoline Wantz (Rennes, 2018)

Milene Franzetti (Rennes, 2018)

Melissa Lallier (Rennes, 2018)

Alexandre Quelhas (Rennes, 2017)

Dylan Chapeau (Rennes, 2017)

Andy Poupon (Rennes, 2015)

Amanda Mendes Silvia (Canada-Brazil Ciência Sem Fronteiras (CsF) Scholarship Program, 2014)

Justine Vinet (Rennes, 2014)

Clair Languitin (Rennes, 2014)

Julient Vinet (Rennes, 2015)

Soufyan Jerhaoui (Rennes, 2013)