Date: Friday, 3 May 2019

Venue: Seminar Room 1, G/F
Laboratory Block, Faculty of Medicine Building
21 Sassoon Road, Hong Kong

Time: 5:00 p.m.

Title: Investigating the contribution of Epstein-Barr virus infection in the development of nasopharyngeal carcinoma using humanized mice model
Speaker: Miss HUANG Chor Mei Shaina (MPhil candidate)

Summary:
Undifferentiated NPC is nearly 100% associated with EBV infection and is heavily infiltrated with leukocytes. It is likely that NPC development may involve the interplay of EBV infection and the infiltrated leukocytes. Humanized mice model offers a platform to study the interactions between human immune cells and EBV-infected NPC cells. Reconstitution of human immune system in NSG mice was achieved by engraftment of CD34+ hematopoietic stem cells. Our laboratory has established different NPC cell lines to understand the contributions of EBV infection in affecting the growth of NPC in humanized mice. Preliminary results showed that EBVpos NPC tumours formed in humanized mice were heavily infiltrated with leukocytes, while EBVneg NPC tumours formed were smaller and with less leukocyte infiltration. Further multiplex immunohistochemistry and FLOW analysis will reveal the differences in components present in the tumours and to provide insights on the roles of EBV in fostering the microenvironment in NPC.

Title: Fucosyltransferase 1 (FUT1) sustains cancer stemness phenotype in hepatocellular carcinoma under glucose restriction stress
Speaker: Miss LOONG Ho Chun Jane (PhD candidate)

Summary:
The core of the hepatocellular carcinoma (HCC) tumor bulk is usually poorly vascularized and glucose level gradually decreases from the periphery to the interior. Herein, we showed that glucose deprivation enhanced the cancer stemness properties in HCC cells. RNA-seq analysis found glucose deprivation to enrich for expression of FUT1. Clinically, we found FUT1 to be frequently overexpressed in human HCC and its expression to positively correlate with aggressive clinical features. Functionally, FUT1 overexpression enhanced cancer stemness properties in HCC cells including their functional abilities to self-renew, initiate tumors and resist standard therapy; while FUT1 knockdown yielded opposing effects. Mechanistically, we found ATF4 to bind to the promoter of FUT1 and drive its transcriptional activity. In hope to identify the downstream mechanism by which FUT1 mediates HCC stemness, we have now carried out TAP-MS and RNA-seq analyses; and are also in the midst of carrying out fucosylated peptide profiling. Combinatorial analysis of these datasets will provide a more holistic overview of FUT1’s interacting partners, targets that FUT1 modifies via fucosylation and signaling pathways that it controls. Work is currently underway to test, as a proof-of-concept, the efficacy of 2-D-Gal in combination with standard therapy, for possible HCC treatment.

ALL ARE WELCOME