10/15/2024
By Kwok Fan Chow

The Kennedy College of Science, Department of Chemistry, invites you to attend a Ph.D. Dissertation defense by Sharon Shechter entitled “Kinases: Have We Truly Explorred It All?”

Degree: Doctoral
Location: Olney, Room 518
Date: Monday, Oct. 28, 2024
Time: 2 p.m.

Committee Chair:
Prof. Matthew Gage, Department of Chemistry, University of Massachusetts Lowell

Committee Members:
Prof. Valeri Barsegov, Department of Chemistry, University of Massachusetts Lowell
Prof. Hwai-Chen Guo, Department of Biological Sciences, University of Massachusetts Lowell
Prof. Jin Xu, Department of Chemistry, University of Massachusetts Lowell

Abstract:
Kinases serve as regulatory signaling proteins and are crucial for various biological and cellular functions, including cell growth, division, metabolism, signaling, and response to environmental stimuli. They facilitate the transfer of phosphate groups from ATP to specific target molecules—such as proteins, lipids, and carbohydrates—in a process known as phosphorylation. This modification can activate or deactivate target molecules, thereby modulating their function and enabling their participation in cellular signaling pathways. In this dissertation, two protein kinases were highlighted. RIOK1 emerged as a novel potential target in high microsatellite instability (MSI-High) p53 mutant colorectal cancer cells. An integrated analysis using proteomics, bioinformatics, cell genotype, and in vitro experiments determined its effects in colorectal cancer (CRC) MSI-High cell lines depend on p53 and KRAS genotypes. The second kinase investigated was p70S6K, a previously identified anti-cancer target, which we demonstrate as a potential anti-COVID-19 target. A multidisciplinary approach, including in vitro experiments and in silico bioinformatics and cheminformatics analyses, revealed that p70S6K, which operates downstream of the PI3K/mTOR signaling pathway that is often exploited by viruses, could serve as a target for treating COVID-19 infection. These findings highlight the synergy of integrating proteomics, specifically phosphorylation data, with in-silico and wet-bench experiments to reveal non-obvious mechanistic insights into kinases that might otherwise elude expert-level analysis.

All interested students and faculty members are invited to attend.