Jorge A. Bezerra, MD
Photo: Jorge A. Bezerra



Elected 2005

Dr. Bezerra’s research program investigates how developmental defects and abnormal immune response cause biliary diseases in children. Studying biliary atresia, an obstructive and fibrosing cholangiopathy of neonates, he has used a mouse model of virus-induced experimental atresia to dissect the temporo-spatial synergy among cellular and molecular factors that injure cholangiocytes, disrupt the bile duct epithelium, and obstruct the lumen by fibrosis. In mechanistic experiments, he uncovered an abnormal Th1 immune response of myeloid and lymphoid cells that work in synergy to injure extrahepatic bile ducts and a parallel activation the adaptive Th2 response to restore epithelial integrity. Using predictive computer modeling of disease, he uncovered a transcriptional fibrosis signature underlying a poor response to treatment and a role for intracellular glutathione in maintaining matrix homeostasis. He also found that chief among tissue and circulating proteins is matrix metalloproteinase-7, which precisely forecast epithelial injury and the disease phenotype. 

With the goals to develop an in vitro system that is more directly relevant to human biology, he developed novel methods to engineer multi-cellular organoids using primary epithelial and mesenchymal cells from normal- and diseased-human livers. He is using these organoids and powerful in vivo systems to investigate: 1) how perinatal exposure to virus(es) and the postnatal development of intestinal microbiome regulate the innate and adaptive immune systems;  2) mechanisms used by inflammatory signals to promote tissue repair using novel human liver organoids; 3) defects in cell specification and maturation that induce loss of polarity in cholangiocytes, and 4) the paracrine mechanisms used by myofibroblast to aid cholangiocyte proliferation and maintenance of cell junctions.