School of Biomedical Sciences cordially invites you to join the following Post-doctoral Fellow (PDF) Seminar:

Date: 8 October 2025 (Wednesday)
Time: 4:00 pm – 5:00 pm
Venue: Seminar Room 2, G/F, Laboratory Block, 21 Sassoon Road
Host: Dr. Xiang Fang & Dr. Yolanda Liu

Light refreshments will be served. Please register via the below link by 6 October 2025 (Monday):
Registration: https://hku.au1.qualtrics.com/jfe/form/SV_5jyXMWiUjRsUxEO

In vitro co-culture CRISPR screen identifies SMG1 to potentiate T cell-mediated cytotoxicity in hepatocellular carcinoma
Dr. Ka Hei Lam (Post-doctoral Fellow)
[Supervisor: Professor Stephanie Ma]

Despite achieving durable clinical responses in multiple malignancies, the overall response rate to immune checkpoint blockade (ICB) for hepatocellular carcinoma (HCC) patients remains relatively low. Here, we conducted a kinome CRISPR knockout screen and identified SMG1 as a key kinase contributing to immune escape from cytotoxic T cell killing. Bioinformatics analysis revealed that high SMG1 expression correlates with ICB resistance and reduced cytotoxic T lymphocyte (CTL) signature. In vitro and in vivo experiments demonstrated that downregulation of SMG1 reduced tumor burden in an immune-dependent manner, promoting cytotoxic T cell infiltration and response to ICB. SMG1 inhibition also potentiates tumor response to IFN-γ, promoting antigen presentation, and upregulating T cell chemoattractant CXCL9. These findings suggest that targeting SMG1 could improve immunotherapy efficacy in HCC by boosting antitumor immunity.

Motor neuron-specific DLC1-i1 deficiency leads to neuromuscular defects in spinal muscular atrophy
Dr. Tianyuan Shi (Post-doctoral Fellow)
[Supervisor: Professor Martin Cheung] 

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by the loss of the ubiquitously expressed survival motor neuron 1 (SMN1) protein but the mechanism underlying the selective loss of MNs remains unknown. Here, we found that DLC1 isoform 1 (DLC1-i1) is predominantly expressed in MN lineage and its reduced expression in MNs derived from SMA patients’ urine-derived induced pluripotent stem cells (UiPSCs). SMA patients’ UiPSCs-derived neuromuscular organoids (NMOs) showed defects in neuromuscular junctions and increased cell death, which can be recapitulated by DLC1-i1 knockdown NMOs and overexpression of DLC1-i1 can rescue patients’ NMOs. Importantly, gene therapy with DLC1-i1 was more effective than SMN restoration in extending lifespan and improving locomotor activity in SMA mice. Mechanistically, DLC1-i1 enhances SMN2 exon 7 inclusion and promotes ATP production. Altogether, our findings reveal that the neuromuscular defects in SMA are partly mediated by the loss of MN-specific DLC1-i1 and restoration of DLC1-i1 represents a more effective therapeutic approach for SMA.

All are welcome.