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Mar 14, 2024

RPG Seminar (2024-03-14)

Date: 14 March 2024 (Thursday)
Time: 5:00 pm – 6:00 pm
Venue: Cheung Kung Hai Lecture Theatre 1, G/F, William M.W. Mong Block, 21 Sassoon Road
 

5:00 p.m.

Presenter: Tin Yan KOO (PhD candidate)
Primary Supervisor: Prof. Clive CHUNG
Presentation Title: Application of activity-based protein profiling in discovery of cysteine-reactive lead
Abstract: Activity-based protein profiling (ABPP) allows identification of reactive residues on protein targets for functional study and ligand discovery. Cysteine as one of the low-abundance amino acids harboring significant biological roles in life, becomes an attractive target in ABPP and drug targeting sites. Yet, conventional cysteine-reactive probes have their downsides. Utilizing the ABPP approach, we identify CL16, as a RhoA inhibitor which demonstrates anti-tumoral effect in colorectal cancer. Meanwhile, given the inherent downsides of conventional cysteine-reactive probes, we report N-acryloylindole-alkyne (NAIA) as a promising cysteine-reactive probe with improved performance to facilitate drug screening. It enables identification of more previously unreported reactive cysteines. It uniquely discovers CL1 from screening experiment to target Rac1 C178, modulating cell cycle in liver cancer, of which is unfeasible with other cysteine reactive probes. This highlights the quest for more versatile probes to address different biological questions and illustrates the applicability of NAIA in chemoproteomics experiment.

 

5:30 p.m.

Presenter: Sukbum KIM (MPhil candidate)
Primary Supervisor: Prof. Stephanie MA
Presentation Title: Mass spectrometry profiling identifies ENO2 as a driver of lenvatinib resistance in hepatocellular carcinoma
Abstract: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and lenvatinib is a multikinase inhibitor that has been approved by the Food and Drug Administration (FDA) as a first-line treatment for advanced HCC since 2018. Despite this approval, the clinical benefits of lenvatinib are limited, and acquired resistance to the drug is inevitable during HCC treatment. Therefore, it is essential to understand the molecular mechanisms of lenvatinib resistance and explore new therapeutic approaches to overcome this resistance. In this study, proteomics mass spectrometry analysis of two lenvatinib-resistant and their parental lenvatinib-sensitive HCC cell lines identified enolase 2 (ENO2) as a potential contributor to the development of lenvatinib resistance in HCC. The upregulation of ENO2 in HCC was significantly associated with aggressive clinical and stemness features, including overall survival, advanced tumor stage, hypoxia, and stemness signatures. Additionally, ENO2 expression was found to be enhanced under hypoxic conditions. Ongoing research is investigating the functional role and underlying molecular mechanisms associated with ENO2-driven lenvatinib resistance and cellular plasticity in HCC, as well as the role of HIF-1α in regulating ENO2 expression under hypoxia.

ALL ARE WELCOME

Should you have any enquiries, please feel free to contact Jerry Siu at 3917 6912.