31^st International Cell Death Society (ICDS) meeting: “Cell fate and its regulation in health and disease”

Abstract

The annual meetings of the International Cell Death Society (ICDS) bring together leading scientists from around the world to present their research across diverse aspects of cell death, while fostering connections and collaborations with junior scientists, postdoctoral fellows and graduate students. This year, the 31st scientific meeting of ICDS was hosted in Singapore from 28th to 30th May, at the Yong Loo Lin School of Medicine (YLLSOM), National University of Singapore (NUS). The meeting theme centered on cell fate, with each day focusing on one of three key areas: immune regulation, cellular signaling and disease, therapy and ageing.

Introduction

The 31^st annual meeting of ICDS brought together many leading experts and leaders in cell death to present their most recent studies and findings related to human health and disease, including cancer, cardiovascular disease, neurodegeneration, and inflammation. The meeting focused on the dysregulation of cellular and tissue responses to physiological stimuli in diseases, and how insights from these mechanisms could be translated into clinical applications, particularly in the development of targeted therapies. As is the mission of ICDS the program served as a platform for communication among scientists and clinicians, and as a dynamic learning environment for students specializing in research. Hosted annually in different countries, the 31^st ICDS meeting was held in Singapore from 28th to 30th May and was co-hosted by Shazib Pervaiz and Marie-Veronique Clement (Singapore), alongside Zahra Zakeri and Richard Lockshin (USA). Delegates from 17 countries across Australia, Europe, North and South America, Asia, and Africa participated in the program, attracting nearly 100 attendees in total. Over the course of three days, eight sessions were held under the overarching theme of Cell Fate, with daily focuses on Immune Regulation, Cellular Response, and Disease, Therapy and Ageing.

Fig. 1.

The 31st International Cell Death Society Meeting was held at the National University of Singapore between May 28th to 30th, 2025

Symposium Overview

The Award Lectures, chaired by Marie-Veronique Clement (Singapore), commenced with keynote speaker Jerry Chipuk (USA), who emphasized the central role of mitochondrial outer membrane permeabilization (MOMP) in cell death. He outlined the mechanisms regulating BAX-dependent MOMP and apoptosis, offering insights into potential therapeutic targets within the mitochondrial apoptosis pathway. The second keynote lecture, chaired by Raymond Birge (USA), delivered by Shazib Pervaiz (Singapore), highlighted the paradoxical role of oxidative stress in cancer, showing that sub-lethal redox stress can promote cell growth, proliferation, and survival, but can also drive cellular injury. He demonstrated how oxygen-derived radicals regulated cell fate through mechanisms such as non-canonical Bcl-2 activity and PP2A inactivation, and how exploiting the aberrant redox environment of cancer cells, such as through drug-induced hyperactivation of KRAS, offers potential for the development of new targeted therapies. Both speakers were honored with the ICDS Lifetime Award, with Chipuk recognized for his groundbreaking research on mitochondrial dynamics and cancer, and Pervaiz acknowledged for his outstanding contributions to cellular redox metabolism and cell death research for more than three decades and for challenging established dogmas.

Fig. 2.

The 31st ICDS meeting honored lifetime achievement awards to Jerry Chipuk (USA) and Shazib Pervaiz (Singapore)

Symposium Proceedings

Day 1 concluded with Session 1: “Cell Fate and Immunity,” chaired by Ann-Marie Chacko (Singapore). Dmitri Krysko (Belgium) presented data from orthotopic glioma models, showing that dendritic cell vaccines loaded with ferroptotic lysates effectively induced a tumour-specific immune response in mice, an effect dependent on the presence of Calreticulin (CRT) and ATP. Raymond Birge (USA) discussed how phosphatidylserine (PS) exposure in the tumour microenvironment (TME) suppressed anti-tumour immunity via TIM and TAM receptors, and highlighted antibody-based and PS-targeting fusion protein approaches as therapeutic strategies. Marc Diederich (South Korea) demonstrated that immunogenic necrosis of myeloid cells provided a potent approach for generating a CML vaccine, effectively reducing tumour burden, addressing minimal residual disease, and offering a promising avenue for immunotherapy in leukaemia.

Day 2 commenced with Session 2: “Signaling Pathways in Cell Fate,” chaired by Reshma Taneja (Singapore), which focused on mechanisms regulating cell fate. Seamus Martin (Ireland) demonstrated that therapy-induced upregulation of death receptor Fas suppressed entry to senescence, an effect counteracted by stabilization of cFLIPL, a well-known suppressor of death-receptor-initiated apoptosis. Barbara Conradt (UK) presented her findings and updates on apoptosis activation in C. elegans, refining established textbook models. Kanaga Sabapathy (Singapore) reported that p44 (the murine equivalent of human p47, a TP53 isoform) is dispensable for tumour suppression, and functional interaction between p44 and p53 is required for male fertility, as p44/p53 heterozygous mice exhibited increased oxidative stress and germ cell apoptosis, leading to reduced mature sperm production. Yinghui Li (Singapore) revealed that constitutive Fn14 signaling reprograms the transcriptomic and epigenomic landscapes of triple-negative breast cancer (TNBC), enhancing tumour growth and metastasis, and activating TNBC-specific super enhancers (SE), such as NAMPT, to promote metabolic reprogramming and metastasis.

Fig. 3.

Local Organizers at NUS welcomed the world with warm hospitality

Next, Session 3:“Mitochondrial Metabolism and Cell Fate,” was chaired by Thilo Hagen (Singapore). Stephen Chong (Singapore) identified two key mechanisms driving MCL-1-mediated Venetoclax (VEN) resistance in chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML): elevated levels of superoxide and Bcl-2 family protein phosphorylation. He demonstrated that targeting these pathways could resensitize resistant cells. Chandra Dhyan (USA) reported a novel mitochondrial unfolded protein response (MitoUPR) inhibitor that blocks HSP60-ClpP interactions, triggering metabolic stress, destabilizing mitochondrial bioenergetics and suppressing survival signaling in advanced prostate cancer (PCa). Marie Hardwick (USA) showed that the Bcl-xL/Bcl-2 inhibitor ABT-737 disrupts Bcl-xL’s ability to stabilize the mitochondrial membrane and interact with ATP synthase, thereby reducing mitochondrial efficiency under conditions of sudden ATP demand. She underscored the importance of distinguishing between anti-apoptotic functions from mitochondrial energetic functions of Bcl-xL for therapeutic design.

To end the second day, session 4: “Stress Response Signaling in Cell Fate” was chaired by Sharad Kumar (Australia). Anne-Sophie Armand (France) showed that GPRC6A receptor and its ligand Osteocalcin are expressed in tumour-associated macrophages, explored their receptor-ligand role in prostate cancer, and highlighted their potential contribution to cancer progression and bone metastasis. Samuel Katz (USA) examined BOK in tauopathies, identified it as a therapeutic target candidate, and demonstrated its role in neuronal death in murine models overexpressing wildtype or mutant Tau (P301L). John Chua (Singapore) reported that HEBP1 drives progressive neurodegeneration in Alzheimer’s disease by promoting mitochondrial-associated caspase signaling pathway, leading to neuronal death. Eli Arama (Israel) discovered that compensatory growth of the Drosophila wing imaginal disc after ionising radiation, which is widely used in cancer treatment and prevention, is regulated by the balance between Dronc-activating radiation-induced apoptosis-resistant epithelial (DARE) cells and non-Dronc-activating radiation-induced apoptosis-resistant epithelial (NARE) cells. Their interplay ensures balanced tissue regeneration, with implications for treatment resistance and cancer recurrence.

Day 3 began with session 5: “Cell Fate in Oncogenesis and Cancer Therapy” and was chaired by Shazib Pervaiz (Singapore). Marie Arsenian-Henriksson (Sweden) identified the hypoxia-inducible lipid droplet–associated protein (HILPDA) as a key driver of lipid metabolism reprogramming in clear cell renal cell carcinoma (ccRCC), and showed that antioxidants PRDX6 and GSTP1, although important for development, were upregulated in neuroblastoma (NB) and represented potential therapeutic targets in Myc-driven cancers. Alessandro Carrer (Italy) examined cholesterol-mTORC1 dependency in pancreatic ductal adenocarcinoma (PDA), driven by KRAS-induced metabolic reprogramming, and demonstrated that selenorganic compounds such as dibenzyl diselenide (DBDS) induced ferroptosis in PDA cells. Combined with statins, this strategy offered therapeutic potential against PDA. Mengge Yu (Singapore) reported that the BIM deletion polymorphism (BDP), a germline variant, drives chronic myeloid leukaemia (CML) progression by conferring resistance to tyrosine kinase inhibitors in leukaemia stem and progenitor cells. This resistance could be overcome by targeting MCL-1 to restore apoptosis, highlighting BDP as a diagnostic target for tailored therapies. Ying Yu Liang (Singapore) demonstrated the translational application of applied mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) to predict treatment response. Using MS-CETSA, she identified nuclear periphery proteins as initial apoptosis effectors, revealed RNA modification processes underlying fluorouracil resistance, and showed that DNA damage repair pathways are activated in gemcitabine resistance via trans-lesion synthesis.

Session 6: “Therapeutic Targets in Cancer Cell Fate Signaling” was chaired by Marianne Cronje (South Africa). Derrick Ong Sek Tong (Singapore) employed patient-derived stem cell-like glioblastoma cells (GSCs) to uncover new dependencies in Glioblastoma (GBM), aiming to better elucidate its molecular pathogenesis and develop biomarkers to aid patient stratification for precision treatment. Boon Cher Goh (Singapore) examined metastasis and chemoresistance, showing that extracellular vesicles shed by tumour cells carry protein cargo that promotes drug resistance and tumour proliferation in distant lesions. Shruti Bhatt (Singapore) highlighted the essential role of p53 in post-MOMP signaling and demonstrated that therapy resistance in TP53-mutant leukaemia stems from post-MOMP dysregulation, driven by BIRC5/IAP-mediated caspase blockade. Chit Fang Cheok (Singapore) discovered that p53 prevents hyperPARylation in response to DNA damage, and that in its absence, hyperPARylation leads to pronounced nascent DNA degradation at stalled replication forks, resulting in genomic instability. This novel mechanism expanded the tumour-suppressive functions of p53 by establishing it as a key regulator of replication dynamics.

Session 7: “Cell Fate in Homeostasis and Disease Response” was chaired by Lih Wen Deng (Singapore). Franck Oury (France) examined hormonal regulation of brain ageing and neuronal homeostasis via the primary cilia-autophagy axis in the hippocampus, showing that restoring core-primary cilia protein levels improved cognitive impairments in aged mice. He further demonstrated that activation of the PC-autophagy axis required the PC-dependent cAMP response element-binding protein signaling pathway. Ali Shazib (USA) described a non-invasive, multi-modal diagnostic platform for head and neck squamous cell carcinoma (HNSCC), which integrated molecular biomarker detection, patient metadata and machine learning to quickly distinguish HPV-positive and HPV-negative cases with high accuracy, supporting early intervention. Yunus Akkoc (Turkey) observed that CTF1 functioned in breast cancer-derived carcinoma-associated fibroblasts (CAFs) by activating autophagy and promoting migration and invasion of stroma-associated breast cancer cells, with high levels associated with lymph node metastasis. He also emphasized that CTF1 is as crucial as TGFβ in CAF formation, stimulating specific fibroblast activation-related pathways.

Fig. 4.

The 31st annual ICDS meeting showcased the rapid ferment biomedical sciences and cultural experiences of Singapore

Last but not least, Session 8: “Cell Fate in Age-Related Disorders” was chaired by Tugba Bagci Onder (Turkey). Andreas Bergmann (USA) examined the paradoxical apoptosis-induced proliferation (AiP) in Drosophila and reported a non-apoptotic role of the caspase Dronc, which activated NADPH oxidase Duox in a calcium-dependent manner. This generates ROS that recruits macrophages, leading to JNK activation and the release of mitogenic signals driving proliferation. Naiyang Fu (Australia) described how the interaction between Mcl-1 and Trp53 balances proliferation and death in hair follicle stem cells, observing that acute Mcl-1 deletion caused rapid loss of hair follicle stem cells and impaired hair regeneration after depilation, whereas Trp53 deletion or partial loss of Bak rescues these effects. Mick Lee (Singapore) investigated the cardiomyocyte cell state transition and therapeutic regenerative strategies for heart failure using a genome-wide CRISPR screen in human embryonic stem cells (hESCs). He identified NF2 as a key YAP regulator in a pathway relieving early repressive barriers to promote early epithelial-mesenchymal transition towards mesoderm fate, and also reported asparagine synthetase (ASNS) as a novel marker and functional driver of cardiomyocyte dedifferentiation (CMDD). Brian Kennedy (Singapore) concluded the session with a presentation on “The Longevity Revolution,” where he outlined advances in the biology of ageing and emerging therapeutic and preventive strategies aimed at promoting healthier lifestyles and extending lifespan.

Conclusion

The 31^st ICDS provided a platform for the interdisciplinary exchange of research innovations across the spectrum of cell fate, encompassing apoptosis, autophagy, mitochondrial function, regenerative processes, and senescence. Local and international delegates introduced fundamental insights into how cellular outcomes are dysregulated in diseases such as cancer, neurodegeneration, and ageing. They highlighted the mechanisms underlying therapy resistance and described the novel chemotherapeutic strategies discovered to target these vulnerabilities, emphasizing their potential for precision therapies and preventative interventions. Overall, the symposium exemplified the diverse and innovative exchange of ideas shaping the future of medical research and clinical translation. The meeting also highlighted the rapid pace of biomedical research in Singapore and neighboring countries. This highly interactive meeting opened new avenues of research and collaboration and provided a culturally enriching experience for all. The 32^nd annual ICDS meeting will be held in Paris, France in 2026 (https://celldeath-apoptosis.org/).

Authors’ contributions

All authors have read and approved the final version.

Declarations

Competing interests

None of the authors have any conflict of interest to declare.