Dr Xiao-Ming Sun

Xiao-Ming trained as a Pharmacist in the Nanjing College of Pharmacy, Nanjing, China. After a few years working in the China Pharmaceutical Incorporation, he took a 3-year research degree course (MSc) in Pharmacology at the China Pharmaceutical University and worked on the effect of components of a Chinese traditional herb on the metabolism of arachidonic acid and platelet aggregation. After a few years teaching and research in Pharmacology and Toxicology, he gained a 1-year grant from the British Council to train in Toxicology at the MRC Toxicology Unit (Carshalton, Surrey) with Dr. Gerry Cohen followed by a PhD program in Biochemistry studying the nuclear morphological changes and related biochemical events that occur during apoptosis. Following a brief Postdoctoral Fellowship with Prof. David Ross at Colorado University, USA studying the effect of metabolically activated compounds (either environmental toxins or purposely designed drugs) on cellular toxicity/induction of apoptosis, Xiao-Ming rejoined Prof. Gerry Cohen’s group to study the molecular mechanisms of apoptosis. Following Prof. Cohen’s retirement in 2012, Xiao-Ming joined the lab of Prof. Marion MacFarlane where he continues to study the fundamental mechanisms of cell death. He has also applied his extensive experience to the Cross-Unit project exploring fibre-induced toxicity (including mesothelioma), with a focus on understanding mechanisms of apoptosis resistance as an adverse outcome following pathogenic fibre exposure.

Cell death is vital for the survival of multicellular organisms, not only during development, to shape the morphogenesis of tissues and organs, but also in the maintenance of homeostasis in adults. Apoptosis is a mode of cell death defined by a characteristic morphology with distinct cell biological and biochemical features. In toxicology, abnormally induced apoptosis is an indication of the toxicity caused by environmental substances or medicinal products. My research interests focus on the activation mechanism of caspases, key executioners of the apoptotic death program, and their functional analysis. Currently, I am studying the mitochondria-mediated intrinsic cell death pathway with a specific emphasis on the interaction of BCL-2 family members and their role in formation of mitochondrial outer membrane permeability (MOMP) leading to the activation of caspases. For this, we combine our knowledge of the metabolic reprogramming of tumor cells with the regulation of BCL-2 family members to sensitize mesothelioma cells (a clinically incurable cancer related to the inhalation of asbestos or other hazardous fibers) to newly developed, purpose-designed drugs that target the Bcl-2 family. Meanwhile, I am also interested in demonstrating the mechanisms of cardiotoxicity induced by this class of newly designed drugs.

1. Cohen GM, Sun XM, Snowden RT, Dinsdale D, Skilleter DN. Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J. 286 (Pt 2):331-4. 1992
    
2. Sun XM, Cohen GM. Mg2+ -dependent cleavage of DNA into kilobase pair fragments is responsible for the initial degradation of DNA in apoptosis. J Biol Chem. 269(21):14857-60. 1994
    
3. Sun XM and Ross D. Quinone-induced apoptosis in human colon adenocarcinoma cells via DT-diaphorase mediated bioactivation. Chemico-Biological Interactions 100(3):267-276, 1996
    
4. Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM. Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem. 274(8):5053-60. 1999
    
5. Sun XM, Bratton SB, Butterworth M, MacFarlane M, Cohen GM. Bcl-2 and Bcl-xL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac/DIABLO and subsequent inactivation of X-linked inhibitor-of-apoptosis protein. J Biol Chem. 277(13):11345-51. 2002
    
6. Sun XM, Butterworth M, MacFarlane M, Dubiel W, Ciechanover A, Cohen GM. Caspase activation inhibits proteasome function during apoptosis. Mol. Cell. 14(1):81-93. 2004
    
7. Vogler M, Dinsdale D, Sun XM, Young KW, Butterworth M, Nicotera P, Dyer MJ, Cohen GM. A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells. Cell Death Differ. 15(5):820-30. 2008
    
8. Chernova T, Sun XM, Powley IR, Galavotti S, Grosso S, Murphy FA, Miles GJ, Cresswell L, Antonov AV, Bennett J, Nakas A, Dinsdale D, Cain K, Bushell M, Willis AE & MacFarlane M. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease. Cell Death Differ. 23, 1152–1164. 2016
    
9. Chernova T, Fiona Murphy A, Galavotti S, Sun XM, Powley IR, Grosso S, Schinwald A, Zacarias-Cabeza J, Dudek KM, Dinsdale D, Le Quesne J, Bennett, Nakas A, Greaves P, Poland CA, Donaldson K, Bushell M, Willis AE, and MacFarlane M. Long-Fiber Carbon Nanotubes Replicate Asbestos-Induced Mesothelioma with Disruption of the Tumor Suppressor Gene Cdkn2a (Ink4a/Arf). Current Biology 27, 3302–3314. 2017
    
10. Chen T, Sun XM, Wu L. High Time for Complete Ban on Asbestos Use in Developing Countries. JAMA Oncol. 5(6):779-780, 2019