Regulation of apoptosis and compensatory cell proliferation in tissue homeostasis
Tissue homeostasis is the maintenance of normal tissue morphology and function under physiological or pathological conditions. In multi-cellular organisms, this requires coordinated cell death (e.g. apoptosis), cell proliferation and cell differentiation. On the one hand, in response to stresses such as radiation and accidental injury, cells can get damaged and are removed by a self-destruct mechanism called apoptosis. On the other hand, surprisingly, apoptotic cells can actively induce proliferation of their neighboring cells to compensate for the cell loss. This phenomenon is termed apoptosis-induced compensatory cell proliferation (apoptosis-induced proliferation). Therefore, both apoptosis and apoptosis-induced proliferation are critical for tissue recovery and organismal survival. Under pathological conditions, mis-regulated apoptosis or apoptosis-induced proliferation can lead to many human diseases including degenerative disorders and cancer. Our research is to investigate the cellular control of apoptosis and apoptosis-induced proliferation, especially how these cellular processes are coordinated and regulated.
Work by us and others has revealed that stress-induced apoptotic cells can send growth signals to trigger compensatory cell proliferation through a non-apoptotic function of caspases, a family of cysteine-proteases that normally execute apoptosis. Intriguingly, we also discovered that apoptosis can induce cell proliferation through distinct mechanisms in different developmental contexts, e.g. in proliferating versus differentiating tissues. However, it is not yet clear how apoptosis-induced proliferation is regulated at the molecular level following activation of caspases, and why distinct mechanisms are employed in a cell context-dependent manner. By taking advantages of Drosophila as a genetically tractable model organism, we have developed unique assays to systematically identify and characterize novel regulators of apoptosis-induced proliferation. Dissecting its underlying regulatory mechanisms will make substantial contributions to our understanding of the cellular strategies and genetic pathways used to maintain tissue homeostasis in response to apoptosis. Our long-term research goal is to elucidate the relevance of apoptosis-induced proliferation in tissue regeneration and tumorigenesis.
Dr Fan’s research is supported by the EU FP7 Marie Curie Actions (CIG) and the Biotechnology and Biological Sciences Research Council in the UK.