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Yongke Lu

Yongke Lu, PhD
Assistant Professor

luy@marshall.edu

 I have been studying alcohol-associated fatty liver disease (ALD) since 2005. A few years ago, we found that mouse cytochrome P450 2A5 (CYP2A5), the ortholog of human CYP2A6, was induced by ethanol feeding. Ethanol induction of CYP2A5 is regulated by Nrf2, a redox-sensitive transcription factor, implicating that CYP2A5 is an antioxidant enzyme. Experiments with cyp2a5-/- mice demonstrated that CYP2A5 is protective against ALD. Nicotine is mainly metabolized by CYP2A5 and CYP2A6. We found that nicotine enhanced alcoholic fatty liver, which is due to oxidative stress in the process of CYP2A metabolizing nicotine. Interestingly, nicotine and its metabolite cotinine upregulate expression of cdkn1a gene, which encode P21 protein, an inhibitor of cell proliferation. We are applying cdkn1a-/- mice and liver stem cells to examine the role of suppressed hepatocyte proliferation on nicotine-enhanced ALD.

Recently, my research interests have been extended to obesity and nonalcoholic fatty liver disease (NAFLD). We found that HFD-induced NAFLD was more pronounced in cyp2a5-/- mice than in WT mice, suggesting that CYP2A5 also protects against NAFLD. Interestingly, PPARα was up-regulated in cyp2a5-/- mice, and PPARα-deficient cyp2a5-/- mice (i.e. pparα-/-/cyp2a5-/- mice) enhanced HFD-induced NAFLD ranging from steatosis, to steatohepatitis and fibrosis. We are studying on the molecular mechanisms by which steatotic hepatocytes activate hepatic stellate cells (HSC) to promote liver fibrosis. In addition, we also investigate the effect of nicotine on high fat diet-induced obesity and NAFLD.

 

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Dr. Yongke Lu's full listing of publications can be viewed on PubMed.

Most Recent Publications: 

  1. Li Y, Wang K, Zhang P, Huang J, Liu Y, Wang Z, Lu Y, Tan S, Yang F, Tan Y. Pyrosequencing analysis of IRS1 methylation levels in schizophrenia with tardive dyskinesia. Mol Med Rep. 2020 Apr. 
  2. Chen X, Wang K, Cederbaum AI, Lu Y. Suppressed hepatocyte proliferation via a ROS-HNE-P21 pathway is associated with nicotine- and cotinine-enhanced alcoholic fatty liver in mice. Biochem Biophys Res Commun. 2019 Apr 23.
  3. Bi Y, Liu X, Si C, Hong Y, Lu Y, Gao P, Yang Y, Zhang X, Wang Y, Xiong H, Duan Z, Chen Y, Hong F. Transplanted adult human hepatic stem/progenitor cells prevent histogenesis of advanced hepatic fibrosis in mice induced by carbon tetrachloride. Am J Transl Res. 2019.
  4. Wang K, Chen X, Ward SC, Liu Y, Ouedraogo Y, Xu C, Cederbaum AI, Lu Y. CYP2A6 is associated with obesity: studies in human samples and a high fat diet mouse model. Int J Obes (Lond). 2019 Mar.
  5. Chen X, Owoseni E, Salamat J, Cederbaum AI, Lu Y. Nicotine enhances alcoholic fatty liver in mice: Role of CYP2A5. Arch Biochem Biophys. 2018 Nov 1.