Start main content

Dec 03, 2021

RPG Seminar (2021-12-03)

Date: Friday, 3 December 2021

Venue: Cheung Kung Hai Lecture Theatre 2, G/F, William M.W. Mong Block, 21 Sassoon Road, Pokfulam, Hong Kong

Time: 5:00 p.m. - 6:00 p.m.

5:00 p.m.

Speaker: Mr. Wai Yin LUI (PhD candidate)
Primary Supervisor: Prof. Dong-Yan JIN
Presentation Title: SARS-CoV-2 non-structural protein 1 (NSP1) facilitates viral replication through activating transcription factor NFAT
Abstract: SARS-CoV-2 has led to more than 253 million reported infection cases and claimed more than 5 million lives around the world. Here we investigated the potential role of NSP1 in viral replication and confirmed that SARS-CoV-2 NSP1 facilitates viral replication through activating the transcription factor Nuclear Factor of activated T-cells (NFAT). NSP1 can induce NFAT-Luciferase reporter activity in multiple cell models. The overexpression of cellular transcription factor NFAT would assist wild-type SARS-CoV-2 viral replication. Through Bacterial Artificial Chromosome recombineering, we have deleted NSP1 from SARS-CoV-2 genome and produced NSP1-deleted SARS-CoV-2 virions (DelNSP1) for infection assay. With in-trans supplementation of NFAT protein, DelNSP1 virion demonstrated more efficient viral replication. These data suggested that NSP1 facilitates SARS-CoV-2 replication through activating cellular transcription factor NFAT. 

5:30 p.m. 

Speaker: Miss Ki Fong MAN (PhD candidate)
Primary Supervisor: Dr. Stephanie Kwai Yee MA
Presentation Title: ELF3-mediated activation of SPINK1 drives stemness and chemoresistance of CD133+ hepatocellular carcinoma 
Abstract: Intratumor molecular heterogeneity of hepatocellular carcinoma (HCC) is partly attributed to the presence of cancer stem cells (CSCs), which we now know represents a critical root of tumor recurrence and therapy resistance. CD133 is known to represent an important functional marker of liver CSCs. Yet unfortunately, CD133 is not specific to HCC, but is also expressed in the regenerating liver. Identifying critical factors expressed specifically in liver CSCs, but not in liver normal stem/progenitor cells may offer important therapeutic opportunities. RNA-seq profiling comparing sorted CD133+ and CD133- subsets of regenerating liver induced by DDC diet and HCC induced by either DEN+CCL4 or hydrodynamic tail vein injection of oncogenic plasmids identified Serine Proteinase Inhibitor Kazal Type I (SPINK1) to be distinctly expressed in the HCC CD133+ subpopulation. SPINK1 overexpression is a poor prognostic indicator for HCC. The epithelial cell-specific transcription factor ELF3 drove SPINK1 transcription via directly binding to its promoter. SPINK1 inhibition by knockdown or a specific monoclonal antibody (mAb) mitigated tumor initiation, self-renewal and chemoresistance. Our finding suggests SPINK1 to play a critical role in hepatocarcinogenesis and SPINK1 mAb may represent a novel therapeutic option for HCC, targeting at the CD133 CSC tumor root.



Should you have any enquiries, please feel free to contact Miss Cynthia Cheung at 3917 9748.