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Lixin                          Zhu

Lixin Zhu PhD

Department of Pediatrics

Assistant Professor

Specialty/Research Focus

Cytoskeleton and cell motility; Genomics and proteomics; Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular and Cellular Biology; Pathophysiology; Regulation of metabolism

 
Professional Summary:

1, Mechanism and regulation of gastric acid secretion.
Regulation of gastric acid secretion is the major treatment of many GI diseases including GERD, gastric, duodenal and esophageal ulcers. The spending in treating these conditions is substantial.
The gastric parietal cell, lining the lumen of the stomach, is responsible for the secretion of isotonic HCl (0.15M) into stomach. One ATP is consumed for every proton secreted into the stomach lumen and a lot of proton pump (H,K-ATPase, the alpha and beta subunits of this enzyme were discovered in 1967(1) and 1990(2)) is required for this job. To accommodate these many proton pumps, the apical plasma membrane, in the resting state, is expanded in the form of numerous invaginations which express relatively short microvilli, and a large compartment of cytoplasmic membranes, commonly called tubulovesicles, fully loaded with proton pumps. Upon stimulation by hismatine initiated PKA signaling, these tubulovesicles traffic to and fuse with apical membrane, forming densely packed microvilli comparable to those found on the brush border membrane of small intestine. This intracellular trafficking and fusion events bring proton pumps to their post for active acid secretion. In time, these proton pumps are brought back into the cytoplasm (by way of endocytosis) for a reliable mechanism to turn off acid secretion. Although the membrane recycling theory was raised a long time ago(3), there are still many major gaps in the understanding of the mechanism for the regulation of acid secretion, which are the research interests of our laboratory. Techniques employed include isolation and primary culture of gastric parietal cells, measurement of acid secretion, fractionation of different membranes by differential and gradient centrifugation.
2, Using gastric parietal cell model to study general cell biological questions: how membrane trafficking is regulated by small G-proteins, how filamentous actin supports the dynamic change of microvilli on apical membrane.
The parietal cell has a remarkably large volume of intracellular membrane trafficking adapted to the elegant mechanism for the regulation of acid secretion. This means that this cell is abundant in those protein machineries required for membrane trafficking and fusion, exocytosis and endocytosis. For instance, no other cell type expresses the amount of syntaxin3 found in parietal cell. Therefore, parietal cell is the top choice for elucidating many of the core questions in cell biology. Techniques used to attack these questions include immunoabsorption, differential ultra-centrifugation, IMAC, 2D-electrophoresis, LC-MSMS, and confocal microscopy.
3, Pathogenesis of Nonalcoholic Steatohepatitis (NASH)
NASH research is funded by the Peter and Tommy Fund. NASH is a disease of the liver that is associated with obesity and adult onset, or type II, diabetes. NASH is not a benign disease. Many people with NASH have a shorter life expectancy than those who no not have NASH. NASH is associated with cirrhosis and is the third most common reason for liver transplantation in adults. No one knows what causes NASH, but it is known that in obese people there is increased fat in the liver. In addition to fat, cells that cause inflammation are found in the liver in patients with NASH. It is thought that these inflammatory cells may cause liver damage that results in fibrosis, cirrhosis and ultimately liver failure. The purpose of this research is to understand the relationship between obesity and the molecular factors that control inflammation so the interaction of the two can be better understood and treatments developed.
NASH and alcoholic steatohepatitis share many histological features. Both NASH and alcoholic steatohepatitis patients exhibit macrovesicular and microvesicular fat in hepatocytes. The number and size of Mallory bodies, and the pattern of pericellular fibrosis are also indistinguishable between two disease groups. Previous studies suggested that intestinal bacteria produced more alcohol in obese mice than lean animals. Therefore, we hypothesized and provided the first molecular evidence that alcohol metabolism contributes to the pathogenesis of NASH (Baker et al, 2010).
Fatty liver is a prerequisite for the development of NASH. The homeostasis of hepatic lipid depends on the dynamic balance of multiple metabolic pathways. Previous studies focusing on individual pathway or enzyme drew conflicting conclusions on the molecular mechanism for the accumulation of lipid in hepatocytes. With a high through-put technique, we compared all the major pathways in parallel. We are expecting to publish the exciting results in the near future.
Oxidative stress is believed to be a major factor mediating the transition from simple steatosis to NASH. The prevention or mitigation of oxidative stress in patients with simple steatosis could prevent NASH. Our current research examines two facets of this problem: 1) what are the molecular mechanisms causing oxidative stress; 2) what are the molecular mechanisms that our body take to fight oxidative stress. Many novel findings have been observed in the lab and we are in the process of confirming these observations..
4, Pathogenesis of Inflammatory Bowel Diseases (IBD)
The etiology of IBD is unknown, but a body of evidence from clinical and experimental observation indicates a role for intestinal microflora in the pathogenesis of this disease. An increasing number of both clinical and laboratory-derived observations support the importance of luminal components in driving the inflammatory response in Crohn‘s disease.
Members of the Toll-like receptor family are key regulators of both innate and adaptive immune responses. These receptors bind molecular structures that are expressed by microbes but are not expressed by the human host. Activation of these receptors initiates an inflammatory cascade that attempts to clear the offending pathogen and set in motion a specific adaptive immune response. Defects in sensing of pathogens or mediation of the inflammatory cascade may contribute to the pathophysiology of disease and injure the host by activating a deleterious immune response, such as in inflammatory bowel disease. The focus of this research is to identify specific toll-like receptor mutations that may be associated with the development of inflammatory bowel disease.

Education and Training:
  • PhD, Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology (2001)
  • BS, Biochemistry and Molecular Biology, Nankai University, with Honors (1995)
Employment:
  • Assistant Professor, University at Buffalo (2009-present)
  • Post Doctoral Fellow, University of California at Berkeley (2002–2009)
  • Assistant Scientist, Shanghai Institute of Biochemistry and Cell Biology, China (2001–2002)

Research Expertise:
  • Cell Biology: Mechanism and regulations of gastric acid secretion; hepatitis associated with metabolic syndrome; intracellular trafficking; cytoskeleton.
  • Molecular biology: Construction of recombinant plasmids, recombinant adenovirus, recombinant vaccinia virus; protein identification by mass spectrometry, phosphorylation identification by mass spectrometry; FRAP and FRET analysis.

Journal Articles:
See All (49 Total) >
Abstracts:
  • Feng Q, Baker SS, Liu W, Arbizu RA, Aljomah G, Khatib M, Nugent CA, Baker RD, Hu Y, Zhu L. Combination of Geniposide and Chlorogenic Acid May Reverse NASH Pathogenesis by Improving Gut Barrier Function. Hepatology. 2014; 60(1).
  • Patel RA, Baker SS, Liu W, Desai S, Alkhouri RH, Kozielski R, Mastrandrea LD, Sarfraz S, Cai W, Vlassara H, Patel MS, Baker RD, Zhu L. Effect of Dietary Advanced Glycation End Products on Mouse Liver. PLoS ONE. 2012; 7(4).

Presentations:
  • "Novel Mechanism for Tumorigenesis Associated with Chronic Proton Pump Inhibitor (PPI) Intake" , Longhua Hospital Shanghai University of Traditional Chinese Medicine (2015)
  • "Elevated Irisin Expression in NASH Livers" Scholarly Exchange Day, University at Buffalo (2015)
  • "Overexpression of Bile Acid Synthesis Genes in Pediatric NASH" Digestive Disease Week, American Gastroenterology Association (2015)
  • "Systemic Analysis of NAFLD Transcriptome Revealed Elevated Expression of Alcohol Metabolizing Genes in Mild and Severe NAFLD Livers" Digestive Disease Week, American Gastroenterology Association (2015)
  • "Correlation of Irisin Expression with Inflammatory Markers in Liver" Annual Meeting, Experimental Biology (2015)
  • "Dextrin Sulfate Sodium Enhances High Fat Diet Induced Insulin Resistance in Rats" Annual Meeting, Experimental Biology (2015)
  • "Elevated Irisin Expression in NASH Livers" Annual Meeting, Experimental Biology (2015)
  • "Increased Insulin Resistance by Dextran Sulfate Sodium is Associated with Increased D-Amino Acids and Lipopolysaccharides in Rats" Annual Meeting, Experimental Biology (2015)
  • "Apolipoprotein A-V Gene Expression in Non-Alcoholic Steatohepatitis" The Liver Meeting, American Association for the Study of Liver Diseases (2014)
  • "Combination of Geniposide and Chlorogenic Acid May Reverse NASH Pathogenesis by Improving Gut Barrier Function" The Liver Meeting, American Association for the Study of Liver Diseases (2014)
  • "Elevated Irisin Expression in NASH Livers" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (2014)
  • "PON1 Gene Expression Correlates with the Degree of Fibrosis in Non-Alcoholic Steatohepatitis" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (2014)
  • "Serum Alpha-1-Antitrypsin Levels Do Not Predict Liver Inflammation in Children with NASH" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (2014)
  • "Genes of Alcohol Metabolism in Patients with Simple Steatosis and NASH" Digestive Disease Week, American Gastroenterology Association (2014)
  • "Non-Transferrin Bound Iron Transporter ZIP 14 in the Liver of Pediatric Non-Alcoholic Steatohepatitis Patients" Digestive Disease Week, American Gastroenterology Association (2014)
  • "Potassium Channel KCNJ15 is Required for Histamine Stimulated Gastric Acid Secretion" Digestive Disease Week, American Gastroenterology Association (2014)
  • "Novel Pathway for Iron Deficiency in Pediatric Non-Alcoholic Steatohepatitis" Experimental Biology 2014 (2014)
  • "Potassium Channel KCNJ15 Plays a Critical Role in Gastric Acid Secretion" Experimental Biology 2014 (2014)
  • "D-Amino Acid Oxidase and Peptidoglycan Recognition Protein-2 Gene Expression in Pediatric Non-Alcoholic Steatohepatitis" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (2013)
  • "Role of Alcohol in the Pathogenesis of NAFLD" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (2013)
  • "D-Amino Acid Oxidase Gene Expression in Non-Alcoholic Steatohepatitis" Digestive Disease Week, American Gastroenterological Association (2013)
  • "Serum Endotoxin is not Associated with Pediatric Non-Alcoholic Steatohepatitis" Digestive Disease Week, American Gastroenterological Association (2013)
  • "Systematic Analysis of the Gene Expression in the Livers of Nonalcoholic Steatohepatitis: Implications on Potential Biomarkers and Molecular Pathological Mechanism" Annual Meeting, Experimental Biology (2013)
  • "Characterization of the Gut Microbiome in Nonalcoholic Steatohepatitis (NASH) Patients: a Liaison Between Endogenous Alcohol Production and NASH" Annual Meeting, American Association for the Study of Liver Disease (2012)
  • "Correlation of Iron Related Genes and Oxidative Stress in Non-Alcoholic Steatohepatitis" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (2012)
  • "Paraoxonase Gene Expression in Patients with Inflammatory Bowel Disease" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Young Investigator Award (2012)
  • "The Role of Activated Protein Kinase in Pediatric Nonalcoholic Steatohepatits (NASH)" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (2012)
  • "Adenosine Monophosphate-Activated Kinase (AMPK) Activity in Pediatric Non-Alcoholic Steatohepatitis (NASH) Livers" Research Day, University at Buffalo (2012)
  • "Correlation of Iron Related Genes and Oxidative Stress in Non-Alcoholic Steatohepatitis" Research Day, University at Buffalo (2012)
  • "Impact of Paraoxonase 1 (Pon1) in Pediatric Non-Alcoholic Steatohepatitis (NASH) Livers" Research Day, University at Buffalo (2012)
  • "Inhibition of Lysosomal Enzyme Activites by Proton Pump Inhibitors" Digestive Disease Week, American Gastroenterological Association (2012)
  • "Paraoxonase Gene Regulation by Oxidative Stress and Steroids in CaCo-2 Cells" Research Day, University at Buffalo (2012)
  • "Effect of Dietary Advanced Glycation End Products on Mouse Liver" Annual Meeting, Federation of American Societies for Experimental Biology (2012)
  • "Impact of Paraoxonase 1 (Pon1) in Pediatric Non-Alcoholic Steatohepatitis (NASH) Livers" Annual Meeting, Pediatric Academic Societies (2012)
  • "Impact of Paraoxonase 1 (Pon1) in Pediatric Non-Alcoholic Steatohepatitis" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (2011)
  • "Paraoxonase Gene Expression in Patients with Inflammatory Bowel Disease" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (2011)
  • "RUNX3 Expression in Inflammatory Bowel Disease" Annual Meeting, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (2011)
  • "Elevated Paroxonase 1 (Pon 1) Activity in Pediatric Non-Alcoholic Steatohepatitis (NASH) Livers" Digestive Disease Week, American Gastroenterological Association (2011)
  • "Acid Secretion Associated Translocation of KCNJ15 in Gastric Parietal Cells" 50th Annual Meeting, American Society for Cell Biology (2010)
  • "Hemoglobin is a Possible Antioxidant in Hepatocytes" 50th Annual Meeting, American Society for Cell Biology (2010)
See All (40 Total) >

Clinical Specialties:
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Contact Information

University at Buffalo School of Medicine and Biomedical Sciences
3435 Main Street
413 Biomedical Research Building
Buffalo, NY 14214
Phone: (716) 829-2191
Fax: (716) 829-3583
Email: lixinzhu@buffalo.edu


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