Xiao Zhao, MD
- Assistant Professor of Medicine
My long-term goal is to understand how cellular heterogeneity contributes to the pathogenesis of human liver disease using cholangiocyte biology as a platform. It is increasingly evident that cholangiocytes comprise a highly dynamic population of cells with morphologically and functionally distinct subtypes that arise from different developmental origins. Similarly, cholangiopathies refer to a diverse group of disorders that impair biliary cellular homeostasis with varying etiologies and pathology. The overarching vision of my research program will be to understand how these cells differ and the molecular mechanisms underlying cell type-specific properties and associated disease phenotypes. My earlier work focused on elucidating the molecular mechanisms of biliary atresia (BA), a neonatal cholangiopathy, by utilizing a newly identified plant electrophile (biliatresone) that was linked casually to naturally occurring BA epidemics in newborn livestock. This work has resulted in three major advances: (i) a novel in vivo model of BA; (ii) unprecedented insights into mechanisms underlying early cholangiocyte injury; (iii) how cell type-specific characteristics can drive a biliary disease phenotype. I joined the faculty at Columbia University Vagelos College of Physicians and Surgeons as Assistant Professor of Medicine (Tenure Track) in Jan 2020. Current and future research efforts at Columbia will be focused on further defining the role of aberrant stress signaling in modulating cholangiocyte injury, elucidating the molecular mechanisms underlying cell type-specific stress responses and developing additional models of human BA.
Zhao X, Lorent K, Escobar-Zarate D, Rajagopalan R, Loomes KM, Gillespie K, Mesaros C, Estrada M, Blair I, Winkler J, Spinner NB, Devoto M, Pack M. Protein Quality Control is a Risk Factor and Therapeutic Target in Toxin-Induced Biliary Atresia. 2019 BioRxiv 821967 doi: https://doi.org/10.1101/821967
Estrada MA, Zhao X, Lorent K, Kriegermeier A, Nagao SA, Berritt S, Wells RG, Pack M, Winkler JD. Synthesis and Structure-Activity Relationship Study of Biliatresone, a Plant Isoflavonoid That Causes Biliary Atresia. ACS Med Chem Lett. 2017; 9(1):61-64. PMID: 11149923
Zhao X, Lorent K, Wilkins BJ, Marchione DM, Gillespie K, Waisbourd-Zinman O, So J, Koo KA, Shin D, Porter JR, Wells RG, Blair I, Pack M. Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish. Hepatology. 2016; 64(3):894-907. PMID: 27102575