Date：23 July (Friday)
Time: 09:00 – 10:30 (GMT+8)
Mien-Chie Hung, Ph.D. is the President for China Medical University in Taichung, Taiwan. He was vice president for basic research and professor and chair of the Department of Molecular and Cellular Oncology at The University of Texas MD Anderson Cancer Center from 2010-2019. Dr. Hung is a basic scientist with a keen translational vision and especially his recent research effort has significantly contributed to understanding the biology of cancer and to developing combinational cancer therapies to overcome resistance. Up to date, Dr. Hung has published more than 571 peer-reviewed articles, of which over 150 were published in journals with impact factor 10 or above. His lifetime h-index surpasses 152 (Google Scholar). He is one of members of Selection Committee for Tang Prize in Biopharmaceutical Science category and is one of the founding Editorial Members for Cancer Cell, serves as Editor-in-chief for American Journal for Cancer Research (2015-2017) and Senior Editor for Cancer Research (American Association for Cancer Research, 2018-2021). Dr. Hung was inducted as an Academician of the Academia Sinica in Taiwan in 2002 and as a Fellow in Biological Sciences section, American Association for the Advancement of Science in 2010. His laboratory has a long term commitment to the following research areas: 1) discovery of novel functionality of epidermal growth factor receptor (EGFR) family which may provide useful insight to understand cancer formation and development; 2) identification of cross talks of signal pathways/networks in cancer cells and tumor microenvironment which could potentially predict resistance to target therapy; 3) development of marker-guided targeted therapy including PARP and EGFR inhibitors, immune checkpoint therapy which will effectively treat cancer patients.
We are interested in resistance mechanism to anti-PD-1/PD-L1 treatment, development of effective combination immunotherapy and methodology to enhance PD-L1 detection in clinical setting. In a highly translational study, we identified a link between the ubiquitination and glycosylation pathways that regulate the immunosuppressive activity of PD-L1 (Nature Communications 2016). We showed that glycosylation of PD-L1 is required for its protein stability and interaction with PD-1 and have developed monoclonal antibodies against glycosylation-specific PD-L1 in collaboration with StCube. Impressive therapeutic effect was observed through antibody-drug-conjugate approach (Cancer Cell 2018 & Cancer Res 2020).
We discovered that there is a highly potent synergistic effect of combination therapy of metformin and anti-CTLA4. The therapeutic efficacy could reach to the survival rate of 50-70% by this combination therapy in animal models (Molecular Cell 2018). We also demonstrated that epithelial-mesenchymal transition enhances PD-L1 in cancer stem-like cells by the EMT/β-catenin/STT3-PD-L1 signaling axis (Nature Communications, 2018). My group has conducted a series of vigorous studies to identify additional potential targets to overcome PD-1/PD-L1 resistance and develop effective combination therapy including c-MET inhibitors (Gastroenterology 2019), IL-6/JAK1 pathway (J Clin Invest 2019), Galectin-9 (Nature Comm 2021) and tyro 3 (JCI 2021). These findings provide potential therapeutic strategies to enhance cancer immune therapy efficacy by targeting PD-L1 stabilization to combat multiple cancer types. We developed a method to remove the glycan moieties that potentially mask detection by antibodies on cell surface. We found that improved PD-L1 detection after deglycosylation is associated with response to anti-PD-1/PD-L1 therapy as well as increased PD-L1 signal after deglycosylation is beneficial to therapeutic selection (Cancer Cell 2019).
More recently, We reported a novel PD-L1 function that is independent of its role in immune checkpoint in Nature Cell Biology 2020--PD-L1 in the nucleus harbors a nuclear transcriptional activity and promotes tumor pyroptosis downstream of TNFα.