JULY 8-9, 2023

The 12th Ray Wu Symposium &
Ray Wu Prize Award Ceremony (2023)

Saturday July 8, 2023
*All times and dates displayed are in local Hangzhou time (Beijing, China time)
*All sessions and talks will be delivered in English
Part 1: Opening Ceremony, 2023 Ray Wu Prize and 2023 Gu Xiaocheng Lecture Award Ceremonies
Session Chair: Dr. Tiannan Guo
08:00 - 08:10
Welcome Remarks
Dr. Yigong Shi
President, Westlake University
08:10 - 08:20
Introduction of Ray Wu and Ray Wu Prize
Dr. Xiao-Hong Sun
President, The Ray Wu Memorial Fund
08:20 - 08:40
2023 Ray Wu Prize Award Ceremony
Host: Dr. Kai Lei
08:40 - 08:45
2023 Gu Xiaocheng Lecture Award Ceremony
Host: Dr. Kai Lei
08:45 - 09:10
Group Photo / Break
Part 2: Symposium Section I
Session Chair: Dr. Xiang-Dong Fu
09:10 - 09:40
Chromatin Regulation in Human Diseases
Dr. Yang Shi
Professor, Ludwig Institute for Cancer Research, Oxford University
The past few decades saw the discoveries of most, if not all, enzymes and readers that are involved in chromatin regulation. My lab’s recent efforts have been placed on understanding the roles of these regulators in human diseases. Specifically, we have been interrogating chromatin regulation in enabling response of poorly immunogenic tumors to immune checkpoint blockade therapy and in promoting cancer cell differentiation as a potential therapeutic modality. We have also been exploring chromatin mis-regulation associated with intellectual disability. In this presentation, I will discuss some of these ongoing investigations.
09:40 - 10:05
Receptor-Interacting Protein Kinase 1 (RIPK1), Cell Death and Neurodegenerative Diseases
Dr. Junying Yuan
Professor, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, the Chinese Academy of Sciences
Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) is a master regulator of the cellular decision between pro-survival NF-κB signaling and death in response to a broad set of inflammatory and pro-death stimuli in human diseases. Activation of RIPK1 kinase promotes both cell death and inflammation. Inhibition of RIPK1 has shown efficacy in a wide range of animal models of human diseases. RIPK1 kinase activation has been demonstrated in post mortem human pathological samples of autoimmune and neurodegenerative conditions. An unique hydrophobic pocket in the allosteric regulatory domain of RIPK1 has enabled the development of highly selective small molecule inhibitors of its kinase activity, which have demonstrated safety in pre-clinical models and human clinical trials. Potential applications of these RIPK1 inhibitors for the treatment of monogenic and polygenic autoimmune, inflammatory, neurodegenerative, ischemic, and acute conditions - such as sepsis associated with severe COVID-19 are emerging. I will discuss RIPK1 biology and disease-associated mutations in RIPK1 signaling pathways, highlighting how basic research may be translated into advancement for the treatment of human diseases, particularly neurodegenerative diseases.
10:05 - 10:30
Break
10:30 - 11:10
The Gu Xiaocheng Lecture Award 2022 and 2023 Winner's Reports
10:30 - 10:50
2023 Winner
Dr. Ye Tian, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
Mitochondrial Stress Signaling and Aging
10:50 - 11:10
2022 Winner
Dr. Peng Du, Peking University
Inefficient Splicing Governs XIST RNA-mediated X Chromosome Inactivation
11:10 - 13:30
Lunch and Westlake University Yungu Campus Tour
Part 3: Symposium Section II
Session Chair: Dr. Jianping Wu
13:30 - 13:55
The Synthetic Kidney: From Kidney Organogenesis To Regenerative Nephrology
Dr. Zhongwei Li
Assistant Professor of Medicine, Stem Cell Biology and Regenerative Medicine at the University of Southern California Keck School of Medicine
One out of seven adults develop chronic kidney disease, which frequently leads to kidney failure. For patients with kidney failure, the best treatment option to survive is to get a kidney transplant. However, there is a severe shortage of donor kidneys available for transplantation. Leveraging on the principles of kidney organogenesis, combining stem cell technologies and bioengineering strategies, a synthetic kidney approach is being developed to provide alternative donor kidneys for transplantation.
13:55 - 15:10
2023 Ray Wu Prize Winner's Reports
13:55 - 14:10
Shuangjia Zheng, Sun Yat-Sen University
Intelligent Drug Discovery in Practice on Challenging Targets
14:10 - 14:25
Hanxiao Sun, Peking University
Absolute Quantification of Single-base m6A Methylation in the Mammalian Transcriptome using GLORI
14:25 - 14:40
Dianyu Chen, Westlake University
What does the B Cell Receptor (BCR) Say
14:40 - 14:55
Xiangyu Pan, Sichuan University
Epigenetic Reprogramming and Lineage Plasticity in Tumor Progression
14:55 - 15:10
Liang Chen, East China Normal University
Innovative Base Editors for Highly Accurate Base Conversions
15:10 - 15:30
Break
Part 4: Symposium Section III
Session Chair: Dr. Dangsheng Li
15:30 - 15:55
Topic TBD
Dr. Guoping Zhao
Professor, University of Chinese Academy of Sciences
 
15:55 - 17:10
2023 Ray Wu Prize Winner's Reports
15:55 - 16:10
Rui Zhou, National Institute of Biological Sciences, Beijing
A Signaling Pathway for Transcriptional Regulation of Sleep Amount in Mice
16:10 - 16:25
Yucen Huang, Tsinghua University
An Alternative Mechanism for SARS-CoV-2 RNA Capping and its Inhibition by Nucleotide Analog Inhibitors
16:25 - 16:40
Zhuoning Zou, Peking University
Translatome and Transcriptome Co-profiling Reveals a Role of TPRXs in Human Zygotic Genome Activation
16:40 - 16:55
Bingqing Yao, Westlake University
The Microbe-environment Empowers Cancer Metastasis
16:55 - 17:10
Jiawei Shen, University of Science and Technology of China
Light Modulates Glucose Metabolism
17:10 - 17:35
Tumor Suppressor Loss and Cancer Immune Evasion
Dr. Hongtao Yu
Dean, Westlake University School of Life Sciences
Tumor Suppressor Loss and Cancer Immune Evasion
Hongtao Yu1,2,3,*
1School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; 2Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; 3University of Texas Southwestern Medical Center, Dallas, Texas, USA
*Correspondence: yuhongtao@westlake.edu.cn
Immune evasion is a hallmark of cancer. Tumors evolve to avoid immune destruction and establish an immunosuppressive microenvironment. Immune checkpoint inhibitors block immunosuppressive signals from tumors and allow their targeting by the immune system. We developed a syngeneic teratoma model in mice and conducted genome-wide CRISPR screens to identify genes associated with immune evasion. We found that the loss of pro-apoptotic tumor suppressor genes, such as Trp53, Pten, and Bax, resulted in necrosis and the release of the APOE lipoprotein in teratomas. T cells infiltrating the teratomas were drawn to necrotic regions in Trp53-deficient teratomas, where they accumulated lipids and became stressed and dysfunctional. Similarly, infiltrating T cells in TP53-mutated human glioblastomas displayed an apoptotic state and lipid accumulation. Eradicating necrosis in teratomas or inhibiting lipid uptake by infiltrating T cells restored immunosurveillance. Combining Anti-APOE and anti-PDCD1 antibodies synergistically blocked the growth of Trp53-deficient teratomas. Our results establish a mechanistic connection between the loss of tumor suppressors and cancer immune evasion, and suggest that targeting lipid accumulation in tumor-infiltrating immune cells might enhance immunotherapy of human gliomas.
Key words: Cancer immunoediting; cancer immune evasion; tumor suppressors; teratoma; apoptosis; necrosis; T cell exhaustion; p53; PD-1; Apolipoprotein E
18:00 - 19:50
Networking Dinner
(Subject to separate invitation only)
20:00 - 22:00
Closed-Door Meeting: Career Development Workshop
Session Chair: Dr. Rui Yue
Professor, Tongji University
END OF DAY 1
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Sunday July 9, 2023
*All times and dates displayed are in local Hangzhou time (Beijing, China time)
*All sessions and talks will be delivered in English
Part 1: Symposium Section IV
Session Chair: Dr. Xinhua Feng
08:30 - 08:55
Activation of Antitumor Immunity by Bacteria-derived Signals: Pyroptosis & Beyond
Dr. Feng Shao
National Institute of Biological Sciences, Beijing
Pyroptosis is a proinflammatory cell death executed by the gasdermin-family pore-forming proteins. Among the family, gasdermin D (GSDMD) is cleaved by inflammasome-activated caspase-1 and LPS-activated caspase-11/4/5. The cleavage unmasks the pore-forming domain in GSDMD that perforates plasma membrane. Using a bioorthogonal chemical biology approach allowing controlled delivery of active gasdermin into tumors in mice, we found that pyroptosis of < 15% tumour cells could clear the entire 4T1 mammary tumourgraft, which was absent in immune-deficient mice or upon T-cell depletion. Thus, pyroptosis stimulates potent and effective antitumour immunity. In antitumor immunity, cytotoxic lymphocyte relies on granzymes to kill target cells. We found that natural killer cells and cytotoxic T lymphocytes kill GSDMB-positive cells through pyroptosis, mediated by granzyme A (GZMA) cleavage of GSDMB. IFN-γ upregulates GSDMB expression and promotes pyroptosis of cancer cells including that by CAR-T/TCR-T cells. Thus, gasdermin-executed pyroptosis serves as a cytotoxic lymphocyte killing mechanism, playing an important role in cancer immunotherapy. We recently discovered a novel cytosolic innate immune receptor alpha-kinase 1 (ALPK1) that recognizes a bacterial metabolite ADP-heptose. ADP-heptose-activated ALPK1 phosphorylates the TIFA adaptor, thereby stimulating the NF-κB signaling and proinflammatory cytokine production. I will also discuss the function of ALPK1-TIFA axis in cancer immunity.
08:55 - 09:20
Neural Mechanisms Underlying Ketamine's Mode of Action
Dr. Hailan Hu
School of Brain Science and Brain Medicine, Zhejiang University
Ketamine, the NMDAR antagonist, has revolutionized depression treatment because of its robust, rapid and sustained antidepressant effects. Recently, it was discovered that ketamine inhibits the NMDAR-dependent burst firing of the brain’s anti-reward center, the lateral habenula (LHb). By silencing the LHb bursts, ketamine can disinhibit the aminergic reward circuits downstream of LHb to exert its rapid antidepressant effects.
However, at least three key questions have remained unaddressed. Firstly, does blockade of LHb burst firing contribute to ketamine’s sustained antidepressant effects? Secondly, given that NMDARs are ubiquitously expressed, which specific brain region is the direct target of ketamine? Thirdly, will a drug targeting the same cellular/circuit mechanism of ketamine have similar antidepressant effects? In this talk, I will present our ongoing efforts in addressing these three urgent questions, which will hopefully illuminate a more unified theory on ketamine’s mode of action and inspire new treatment strategies for depression.
09:20 - 09:50
2022 Ray Wu Prize Winner's Reports
09:20 - 09:35
Jia Duan, Chinese Academy of Sciences
Structure of a G Protein-coupled Receptor with GRK2 and a Biased Ligand
09:35 - 09:50
Tianyi Wang, Chinese Academy of Sciences
The Genetic History of Southern East Asia
09:50 - 10:10
Break
Part 2: Symposium Section V
Session Chair: Dr. Qiufu Ma
10:10 - 10:35
Principles for Complexity Evolution of the Life
Dr. Jiarui Wu
Professor, Director, Key Laboratory of Systems Biology, Chinese Academy of Sciences, Hangzhou Institute for Advanced Study, UCAS
The evolution of the life shows the increase of complexity. The three principles applied to guide the complexity evolution of the bio-systmes: (1) Increasing the control capability for regulation of the bio-systems; (2) Increasing the connectivity for the bio-systems. (3) Increasing the compartmentation of the bio-systems.
10:35 - 11:00
Liquid–liquid Phase Separation in Autophagy
Dr. Hong Zhang
Institute of Biophysics, Chinese Academy of Sciences
Our molecular understanding of autophagy mainly originates from studying Atg (autophagy-related) genes identified in yeast. Zhang’s group has established C. elegans as a model to study autophagy and identified a set of metazoan-specific autophagy genes, called Epg genes. Subsequent analysis of these genes has allowed us to understand the unique steps in the much more complex autophagy pathway in multicellular organisms. Dr. Zhang will talk about his group’s recent findings that liquid–liquid phase separation plays important roles in multiple aspects of autophagy, including specification of the autophagosome formation sites in response to ER calcium transients, and triaging of protein cargos for selective degradation.
11:00 - 11:45
2022 Ray Wu Prize Winner's Reports
11:00 - 11:15
Chen Liu, Chinese Academy of Medical Sciences
Decoding Human Lymphopoiesis
11:15 - 11:30
Hui Shen, Peking University
Capturing and Maintenance of Totipotent Stem Cells in vitro
11:30 - 11:45
Haiqing Xiong, Chinese Academy of Medical Sciences & Peking Union Medical College
Developing Single-cell Epigenetic Technologies to Decipher Mechanisms in Cell Fate Decision
11:45 - 12:15
Ray Wu Prize Q&A
Moderator: Dr. Ming Luo
Professor, Department of Chemistry, Georgia State University
12:15 - 13:40
Lunch
Part 3: Symposium Section VI
Session Chair: Dr. Duanqing Pei
14:00 - 14:25
From JAK-STAT to Mechanisms of Inflammation, Immunity and Medicine
Dr. Xin-Yuan Fu
Professor, Director, Laboratory of Human Disease and Immunotherapies, West China Hospital, Sichuan University / GenEros BioPharma, Hangzhou, China
The first two STAT proteins and their activators and JAK (Just Another Kinase) were discovered over 30 years ago as Transcription Activator of p91 (STAT1) and p113 (STAT2) activated by interferon-alpha. The molecular cloning of genes encoding for p91 and p113 revealed the STAT gene family. Finding a SH2 domain in each of STAT proteins indicated STAT proteins are not only transcription factors but also serve as Signal Transducers. Thus the name of STAT (Signal Transducer and Activator of Transcription) was given. Over past 30 years there are over 100,000 publications in the JAK-STAT field, generating an important impact on life sciences. Here we demonstrate STAT5 is key players in regulation of immunity and inflammation. In particular, we revealed a distinct T helper cell subset that produces GM-CSF (Th-GM) and other related cytokines for inflammation. We further developed applications and approaches modulating the Th-GM pathway in drug discovery for inflammatory diseases.
14:25 - 15:10
2022 Ray Wu Prize Winner's Reports
14:25 - 14:40
Lihui Dong, Chinese Academy of Sciences. China National Center for Bioinformation
Cell-cell Interactions Orchestrate the Phenotypic and Functional Diversity of CD8+ T Cells within Tumor Microenvironment
14:40 - 14:55
Zhijie Cao, Peking University
Single-cell Multi-omics Integration and Regulatory Inference through Deep Learning
14:55 - 15:10
Chaoyi Zhang, Massachusetts Institute of Technology (MIT)
The Role of mPFC Microcircuits in Social Competition
15:10 - 15:30
Break
Part 4: Symposium Section VII and Closing Speech
Session Chair: Dr. Kai Lei
15:30 - 16:00
2022 Ray Wu Prize Winner's Reports
15:30 - 15:45
Jiaxing Tan, Zhejiang University
Insights into the Assembly and Directional Control of the Bacterial Flagellar Motor
15:45 - 16:00
Lin Di, Peking University
RNA Sequencing by Direct Tagmentation of RNA/DNA Hybrid
16:00 - 16:25
Molecular Control of T Cell Function in Cancer
Dr. Chen Dong
Shanghai Immune Therapy Institute, Shanghai Jiao Tong University / Institute for Immunology and School of Medicine, Tsinghua University / New Cornerstone Science Laboratory
T cells differentiate into effector cells during pathogen infections, but become dysfunctional by the tumor microenvironments. T cell function is tightly regulated by a combinational co-stimulatory signal; costimulation is needed for T cell differentiation into effector T cells, whereas dominance of co-inhibition results in T cell dysfunction. During the meeting, I will discuss on how T cells are regulated by co-inhibition molecules in their dysfunction induction, and the underlying molecular mechanisms. Moreover, I will discuss on cytokines and transcription factors that determine the function of intra-tumor CD8+ T cells. These knowledges may benefit our understanding on tumor immunity and find new targets in tumor immunotherapy.
16:25 - 16:50
Genetic Innovations Underlying Evolution of Special Animal Traits and their Biomedical Implications
Prof. Wen Wang
Professor, Northwestern Polytechnical University / Kunming Institute of Zoology, Chinese Academy of Sciences
Tempered by millions of years’ adaptation and natural selection, some animals have evolved special traits which are superior than other regular animals. My team has been trying to reveal the genetic innovations underlying ruminants’ special traits, including hypertension tolerance in giraffe, and low cancer rate and full regeneration ability of antler in deer. Antler is the only mammalian organ that is fully regenerated annually.
16:50 - 16:55
Closing Remarks
Dr. Hongtao Yu
Dean, Westlake University School of Life Sciences
END OF DAY 2
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Event Sponsors

Beckman Coulter Hua An 来泊生物 Eppendorf
July 8-9, 2023, Yungu Campus, Westlake University

The 12th Ray Wu Symposium &
Ray Wu Prize Award Ceremony (2023)

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