Aaron Bell, PhD
S424 Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 15261
Dr. Bell’s primary research focus has been in the field of liver regeneration and understanding the signaling networks and transcriptional regulation governing hepatocyte survival, growth and function in liver regeneration, cirrhosis and cancer. Recent work has explored the role of HNF4, a key liver transcription factor, in chronic hepatic failure/cirrhosis. He has shown the importance of HNF4 in maintaining differentiated function in hepatocytes, and that loss of HNF4 perpetuates loss of differentiation and can result in hepatic cell senescence and death. Conversely, administering AAV expressing HNF4 to rats in hepatic failure, resulted in transcriptional reprogramming that saved the rats from hepatic failure and reversed fibrosis. Likewise, more recently, end stage cirrhotic human cells were functionally reprogrammed by expression of HNF4 mRNA.
I have been working for many years to understand the differential regulation of gene expression in hepatocytes during development and in various liver diseases like NAFLD, cirrhosis, PBC, biliary injury-related fibrosis and cancers like HCC and hepatoblastoma, through projects investigating ECM signaling via Integrin-linked Kinase, Glypican3, Notch among others as well as intracellular signaling via HGF/Met, TGFb, PI3K, beta-catenin, wnt et al. I have generated and worked with transgenic mouse models as well as AAV mediated gene targeting to modulate expression of targeted genes and validate their role in liver development, liver regeneration, liver cancer development and metabolic zonation.
View Dr. Bell’s NIH Report on nih.gov
Nishikawa T, Bell A, Brooks J, Locker J, Soto-Gutierrez A, Fox IJ, et al. Resetting the transcription factor network reverses terminal chronic hepatic failure. Journal of Clinical Inv. 125(4):1533-1544 01 Jan 2015.
Tafaleng EN, Mukherjee A, Bell A, Morita K, Guzman-Lepe J, Haep N, Florentino RM, Diaz-Aragon R, Frau C, Ostrowska A et al. Hepatocyte Nuclear Factor 4 alpha 2 Messenger RNA Reprograms Liver-Enriched Transcription Factors and Functional Proteins in End-Stage Cirrhotic Human Hepatocytes. HEPATOLOGY COMMUNICATIONS 5(11):1911-1926 Nov 2021
Guzman-Lepe J, Cervantes-Alvarez E, Collin de l’Hortet A, Wang Y, Mars WM, Oda Y, Bekki Y, Shimokawa M, Wang H, Yoshizumi T, et al. Liver-enriched transcription factor expression relates to chronic hepatic failure in humans. Hepatol Commun 2(5):582-594 May 2018
Haep N, Florentino RM, Squires JE, Bell A, Soto-Gutierrez A The Inside-Out of End-Stage Liver Disease: Hepatocytes are the Keystone. SEMINARS IN LIVER DISEASE 41(02):213-224 May 2021
Jiang A, Bell A, Okabe H, Popovic B, Preziosi ME, Pradhan-Sundd T, Poddar M, Singh S, Monga S, England SG, et al. Loss of Wnt secretion by macrophages promotes hepatobiliary injury following administration of DDC diet. American Journal of Pathology, PMID: 30610845 Jan 2019
Zhang R, Kikuchi AT, Nakao T, Russell JO, Preziosi ME, Poddar M, Singh S, Bell AW, England SG, Monga SP Elimination of Wnt secretion from stellate cells is dispensable for zonation and development of liver fibrosis following hepatobiliary injury. Gene Expr 20 Sep 2018.
Full list of Published work (@ My Bibliography):
Department of Pathology
Pittsburgh Liver Research Center
S414 BST South
200 Lothrop St
Pittsburgh, Pa 15261