We would like to congratulate Dr. Deepak Koirala for successfully completing his PhD from Department of Chemistry & Biochemistry at Kent State University (KSU). Dr. Koirala was working with Dr. Hanbin Mao’s research laboratory at KSU. His PhD research was focused on DNA secondary structures and their interactions with therapeutic drugs at the single-molecule level mainly using high resolution optical tweezers instrument. In addition, he was also involved in DNA nanotechnology and biosensing research in collaboration with Prof. Hiroshi Sugiyama at Kyoto University, Japan. During his PhD, he had 18 publications including 6 first authorship papers in highly reputed journals such as Nature Chemistry, Angewandte Chemie and JACS. He also shared a US patentwith his PhD advisor. For his excellent research contributions, he received the Taylor Research Award and the University Fellowship from KSU. Currently, he is working with Prof. Joseph Piccirilli at The University of Chicago as a postdoctoral scholar.
Dr. Koirala's google scholar profile here.
Congratulations Dr. Koirala ! We would like to wish you all the best for your successful future career.
Here is a brief summary of his research as described in his PhD dissertation.
Human telomeres are associated with genetic integrity, cell proliferation, aging and cancer. Therefore, fundamental understanding of the equilibrium dynamics and the transition kinetics of G-quadruplex structures, their intermediates and other alternative structures formed in the human telomeric DNA sequences and their interactions with small-molecule ligands or proteins are crucial. His PhD research has confirmed the existence of folded intramolecular structures other than the G-quadruplexes in human telomeric sequences under physiologically relevant conditions of Na+ and K+. His results revealed an unprecedented and diverse folding pattern in the human telomere region, which is instrumental for the development of new telomere-targeting small-molecule drugs.
Using force-jump and population deconvolution at sub-nanometer resolution techniques, single-molecule optical-tweezers investigations were able to identify the individual populations associated with human telomeric DNA sequences containing four to eight TTAGGG repeats and precisely follow their kinetics with unprecedented resolutions. A highly complex population equilibrium that contains G-triplex, misfolded G-quadruplexes, and predominant G-quadruplex species were observed. The presence of the misfolded species testified the structural complexity of DNA. The complexity of the system was further reflected by the transition kinetics. The observed population dynamics of telomeric species indicated that in the full-length 3′ end overhang of human telomere, G-quadruplex units with shortest possible TTA loops would be the most prevalent species.
Single-molecule mechanochemical platform discussed in his dissertation also discovered that pyridostatin binds to human telomeric G-quadruplex and promotes its folding kinetics. This method simplified the dissociation constant assay without the requirement for ligand or receptor titration and offered a general platform that can be applied to other biologically relevant ligand-receptor systems. Specifically, his study highlights that G-quadruplexes are important dynamic structures involved in the mechanism of telomere elongation by the action of the enzyme complex telomerase. Furthermore, the mechanochemical information acquired by this system could provide the novel perspectives for drug testing and design in the future. In addition, the extra forces required to unfold ligand bound structures reveal that small-molecule stabilized DNA secondary structures could well interfere with RNA and DNA polymerases during the processes of transcription and replication in vivo.