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The Bezerra Laboratory investigates regulatory mechanisms of liver and biliary injury. One major research focus is preclinical and translational research on biliary atresia, the most common cause of chronic liver disease in children. Investigators have used large-scale expression arrays and bioinformatics to develop transcriptional maps for human and murine biliary atresia. These maps generated hypotheses regarding pathogenic mechanisms of disease. Testing these hypotheses in the laboratory, investigators began dissecting the cellular and molecular basis of neonatal injury and obstruction of extrahepatic bile ducts using unique in vitro and experimental models of disease. Experiments identified key regulatory functions for hepatic dendritic cells and CD8+ and NK lymphocytes in recognition and induction of injury to the bile duct epithelium.
Ongoing experiments are identifying costimulatory signals controlling cell survival during early postnatal development and small molecules regulating biliary diseases. In translational studies, investigators are also applying state-of-the-art approaches to identify the molecular determinants of treatment response in multicenter studies of children with biliary atresia and syndromes of intrahepatic cholestasis.
Moyer K, Kaimal V, Pacheco C, Mourya R, Xu H, Shivakumar P, Chakraborty R, Rao M, Magee JC, Bove K, Aronow BJ, Jegga AG, Bezerra JA. Staging of biliary atresia at diagnosis by molecular profiling of the liver. Genome Med. 2(5):33. 2010.
Santos JL, Carvalho E, Bezerra JA. Advances in biliary atresia: from patient care to research. Braz J Med Biol Res. 43(6):522-7. 2010.
Santos JL, Choquette M, Bezerra JA. Cholestatic liver disease in children. Curr Gastroenterol Rep. 12(1):30-9. 2010.
Mohanty SK, Ivantes CA, Mourya R, Pacheco C, Bezerra JA. Macrophages are targeted by rotavirus in experimental biliary atresia and induce neutrophil chemotaxis by Mip2/Cxcl2. Pediatr Res. 67(4):345-51. 2010.
DeRusso PA, Ye W, Shepherd R, Haber BA, Shneider BL, Whitington PF, Schwarz KB, Bezerra JA, Rosenthal P, Karpen S, Squires RH, Magee JC, Robuck PR, Sokol RJ; Biliary Atresia Research Consortium. Growth failure and outcomes in infants with biliary atresia: a report from the Biliary Atresia Research Consortium. Hepatology. 46(5):1632-8. 2007.
Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck P, Hoofnagle JH. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology. 46(2):566-81. 2007.
Shivakumar P, Sabla G, Mohanty S, McNeal M, Ward R, Stringer K, Caldwell C, Chougnet C, Bezerra JA. Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia. Gastroenterology. 133(1):268-77. Apr, 2007.
de Carvalho E, Ivantes CA, Bezerra JA. Extrahepatic biliary atresia: current concepts and future directions. J Pediatr (Rio J). 83(2):105-20. 2007.
Campbell KM, Arya G, Ryckman FC, Alonso M, Tiao G, Balistreri WF, Bezerra JA. High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease. J Pediatr Gastroenterol Nutr. 44(1):99-103. 2007.
Allen SR, Jafri M, Donnelly B, McNeal M, Witte D, Bezerra J, Ward R, Tiao GM. Effect of rotavirus strain on the murine model of biliary atresia. J Virol. 81(4):1671-9. 2007.
Mohanty SK, Shivakumar P, Sabla G, Bezerra JA. Loss of interleukin-12 modifies the pro-inflammatory response but does not prevent duct obstruction in experimental biliary atresia. BMC Gastroenterol. 6:14. 2006.
Carvalho E, Liu C, Shivakumar P, Sabla G, Aronow B, Bezerra JA. Analysis of the biliary transcriptome in experimental biliary atresia. Gastroenterology. 129(2):713-7. 2005.
Shivakumar P, Campbell KM, Sabla GE, Miethke A, Tiao G, McNeal MM, Ward RL, Bezerra JA. Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-gamma in experimental biliary atresia. J Clin Invest. 114(3):322-9. 2004.
Zhang DY, Sabla G, Shivakumar P, Tiao G, Sokol RJ, Mack C, Shneider BL, Aronow B, Bezerra JA. Coordinate expression of regulatory genes differentiates embryonic and perinatal forms of biliary atresia. Hepatology. 39(4):954-62. 2004.
Bezerra JA, Tiao G, Ryckman FC, Alonso M, Sabla GE, Shneider B, Sokol RJ, Aronow BJ. Genetic induction of proinflammatory immunity in children with biliary atresia. Lancet. 23;360(9346):1653-9. Nov, 2002.
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