Staff Profile

Research Interests

Hepatocytes are the primary cell of the liver, performing the majority of its unique functions, including the metabolism and clearance of xenobiotics. My work is focused on hepatotoxic effects resulting from the exposure to these drugs and chemicals. Using freshly isolated human hepatocytes I investigate the mechanisms of toxicity of drugs and chemicals as well as their cellular uptake and metabolism.

Current research

Investigating the hepatotoxic effects of an environmental xenobiotic.

We recently identified a xenobiotic in the local environment that has the potential to trigger primary biliary cholangitis (PBC). This xenobiotic, 1-octyl-3-methylimidazolium (C8mim; M8OI), is an ionic liquid that we have shown to be both toxic to liver progenitor cells and to be metabolised by human hepatocytes to a metabolite capable of incorporation into an antigen targeted by PBC patient auto-antibodies.

• In vitro and in vivo assessment of the toxicity of M8OI   
• Determining the mechanism of toxicity 
• Route of uptake and metabolism by human hepatocytes
• Xenoestrogenic effects 

• Leitch AC, Abdelghany TM, Probert PM, Dunn MP, Meyer SK, Palmer JM, Cooke MP, Blake LI, Morse K, Rosenmai AK, Oskarsson A, Bates L, Figueiredo RS, Ibrahim I, Wilson C, Abdelkader NF, Jones DE, Blain PG, Wright MC. The toxicity of the methylimidazolium ionic liquids, with a focus on M8OI and hepatic effects. Food and Chemical Toxicology 2020, 136, 111069.
• Alsaeedi F, Wilson R, Candlish C, Ibrahim I, Leitch AC, Abdelghany TM, Wilson C, Armstrong L, Wright MC. Expression of serine/threonine protein kinase SGK1F promotes an hepatoblast state in stem cells directed to differentiate into hepatocytes. PloS One 2019, 14(6), e0218135.
• Fairhall EA, Leitch AC, Lakey AF, Probert PM, Richardson G, DeSantis C, Wright MC. Glucocorticoid-induced pancreatic-hepatic trans-differentiation in a human cell line in vitro. Differentiation 2018, 102, 10-18.
• Fairhall EA, Leitch AC, Lakey AF, Abdelghany TM, Ibrahim I, Tosh D, Kass GE, Wilson C, Wright MC. HNF4alpha expression amplifies the glucocorticoid-induced conversion of a human pancreatic cell line to an hepatocyte-like cell. Biochemical and Biophysical Research Communications 2018, 503(3), 1633-1640.
• Probert PM, Leitch AC, Dunn MP, Meyer SK, Palmer JM, Abdelghany TM, Lakey AF, Cooke MP, Talbot H, Wills C, McFarlane W, Blake LI, Rosenmai AK, Oskarsson A, Figueiredo R, Wilson C, Kass GE, Jones DE, Blain PG, Wright MC. Identification of a xenobiotic as a potential environmental trigger in primary biliary cholangitis. Journal of Hepatology 2018, 69(5), 1123-1135.
• Leitch AC, Lakey AF, Hotham WE, Agius L, Kass GE, Blain PG, Wright MC. The ionic liquid 1-octyl-3-methylimidazolium (M8OI) is an activator of the human estrogen receptor alpha. Biochemical and Biophysical Research Communications 2018, 503(3), 2167-2178.
• Leitch AC, Probert PME, Shayman JA, Meyer SK, Kass GEN, Wright MC. B-13 progenitor-derived hepatocytes (B-13/H cells) model lipid dysregulation in response to drugs and chemicals. Toxicology 2017, 386, 120-132.
• Meyer SK, Probert PME, Lakey AK, Leitch A, Blake LI, Jowsey PA, Cooke MP, Blain PG, Wright MC. Environmental xenoestrogens super-activate a variant murine ER beta in cholangiocytes. Toxicological Sciences 2017, 156(1), 54-71.
• Meyer SK, Probert PME, Lakey AF, Axon AR, Leitch AC, Williams FM, Jowsey PA, Blain PG, Kass GEN, Wright MC. Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse. Toxicology Letters 2017, 273, 55-68.