Ivan Poon group

Apoptosis (programmed cell death) occurs in essentially all tissues as part of development, homeostasis, and pathogenic processes including infection and cardiovascular disorders. Apoptotic cells often disassemble into a type of large extracellular vesicles (L-EVs) called apoptotic bodies. In this project, we aim to determine the molecular machineries that regulate apoptotic body formation.

Extracellular vesicles including apoptotic bodies have been implicated to regulate physiological and pathological processes via the molecules they carry inside or exposed on their surface. However, the importance of generating apoptotic bodies during apoptosis in pathophysiological settings is poorly understood. In this project, the role of apoptotic cell disassembly will be examined in the context of viral infection and cancer progression.

Although apoptotic body formation is a key cellular process for efficient removal of apoptotic debris and intercellular communication in certain disease settings, there is currently a lack of pharmacological compounds available to target this process. Identifying drugs that could modulate apoptotic cell disassembly is likely to provide new research directions that are clinically relevant.

Using a novel flow cytometry-based drug screen approach, we have recently identified a number of drugs that can inhibit or enhance the formation of apoptotic bodies without having an impact on the level of apoptosis. Importantly, some of these drugs are FDA approved and currently being used clinically. In this project, we aim to characterise these novel inhibitors and enhancers of apoptotic cell disassembly in detail, and examine whether these drugs can be used to control the apoptotic cell disassembly process in disease settings.

Although small extracellular vesicles (S-EVs) such as exosomes are often at the forefront of discussion in the EV field, a number of new large EV (L-EV) subsets such as exophers, migrasomes, elongated neutrophil-derived structures, blebbisomes, and large aging-neutrophil-derived vesicles were discovered recently, with each subset exhibiting different biogenesis mechanism and function. Beyond apoptotic bodies (also a type of L-EVs) as described above, we also aim to study the mechanism of biogenesis and functions of other L-EV subsets. The goal is to harness L-EVs for diagnostic and therapeutic applications.