Dr. Oertel is a member of the Division of Experimental Pathology.
Education & Training
Diploma - University of Leipzig, Germany, 1995
PhD - University of Leipzig, Germany, 2000
2000 - PhD, magna cum laude
2008 - Fellow, 16th Annual Summer Training Course in Experimental Aging Research
2008/10 - AFAR Research Grant
A long-term objective of our research is to identify beneficial properties of cells that effectively repopulate the liver, as well as specific characteristics of the hepatic microenvironment that promote tissue replacement. The definitive goal is to restore normal liver function by transplanted cells or by modulating specific pathways in endogenous hepatocytes to improve their regenerative capacity and reconstitute diseased liver.
- We are interested in determining the mechanism(s) of efficient liver repopulation by transplanted epithelial stem/progenitor cells. In these studies, we are collecting tissue samples derived from cell-transplanted liver tissues using laser capture microdissection. To obtain detailed gene expression profiles of signaling pathways that might be involved in augmented liver repopulation by transplanted stem/progenitor cells we will perform RNA-seq analyses on laser-captured donor cell clusters.
- Our studies are focused to determine the repopulation capacity and the therapeutic potential of epithelial stem/progenitor cells and modulated hepatocytes transplanted into fibrotic recipient liver. We have demonstrated that intravenously transplanted stem/progenitor cells can significantly restore severely injured liver mass in an environment with advanced fibrosis/cirrhosis. In addition, we showed that progressive biliary fibrosis stimulates liver repopulation by ectopically transplanted cells, either hepatic epithelial stem/progenitor cells or mature hepatocytes. Our reports also demonstrated that biliary fibrosis stimulates hepatocyte transdifferentiation into biliary epithelial cells. Based on these studies, we will translate the obtained knowledge about the beneficial attributes of stem/progenitor cells to directly target hepatocytes in diseased livers, as well as investigate the process of reprogramming of hepatocytes to induce transdifferentiation.
- We established in vitro-models and identified numerous new activin A target genes, suggesting that this multifunctional cytokine acts as an important regulator of growth control and metabolic homeostasis in the liver. We will continue with our studies to characterize activin A-producing cells in normal and diseased hepatic microenvironments and study the role of activin A as an autocrine/paracrine regulator of hepatocyte growth arrest and senescence.
View Dr. Oertel's NIH RePORT on nih.gov.
View Dr. Oertel's previous publications on PubMed.
- Menthena A, Koehler C, Sandhu JS, Yovchev M, Hurston E, Shafritz DA, Oertel M. Activin A, p15INK4b signaling, and cell competition promote stem/progenitor cell repopulation of livers in aging rats. Gastroenterology 2011; 140: 1009-1020. (PMID: 21147108)
- Oertel M. Fetal liver cell transplantation as a potential alternative to whole liver transplantation? J Gastroenterology 2011; 46: 953-965. (PMID: 21698354)
- Yovchev MI, Dabeva MD, Oertel M. Isolation, characterization and transplantation of adult liver progenitor cells. Methods Mol Biol 2013; 976: 37-51. (PMID: 23400433)
- Yovchev MI, Xue Y, Shafritz DA, Locker J, Oertel M. Repopulation of the fibrotic/cirrhotic rat liver by transplanted hepatic stem/progenitor cells and mature hepatocytes. Hepatology 2014; 59: 284-295. (PMID: 23840008)
- Nishikawa T, Bellance N, Damm A, Bing H, Zhu Z, Handa K, Yovchev MI, Sehgal V, Moss TJ, Oertel M, Ram P, Pipinos II, Soto-Gutierrez A, Fox IJ, Nagrath D. A switch in the source of ATP production and a loss in capacity to perform glycolysis are hallmarks of hepatocyte failure in advance liver disease. J Hepatol 2014; 60: 1203-1211. (PMID: 24583248)
- Yovchev MI, Locker J, Oertel M. Biliary fibrosis drives liver repopulation and phenotype transition of transplanted hepatocytes. J Hepatol 2016; 64: 1348-1357. (PMID: 26855174)
- Okabe H, Yang J, Sylakowski K, Yovchev M, Miyagawa Y, Nagarajan S, Chikina M, Thompson M, Oertel M, Baba H, Monga SP, Nejak-Bowen KN. Wnt signaling regulates hepatobiliary repair following cholestatic liver injury in mice. Hepatology 2016; 64: 1652-1666. (PMID: 27533619)
- Yovchev MI, Oertel M. Fetal liver stem/progenitor cell transplantation: A model to study tissue mass replacement and cell-based therapies. Methods Mol Biol 2017; 1506: 101-115. (PMID: 27830548)
- Khan Z, Yokota S, Ono Y, Bell AW, Oertel M, Stolz DB, Michalopoulos GK. Bile duct ligation induces ATZ globule clearance in a mouse model of alpha-1 antitrypsin deficiency. Gene Expr 2017; 17: 115-127. (PMID: 27938510)
- Haridoss S, Yovchev MI, Schweizer H, Megherhi S, Beecher M, Locker J, Oertel M. Activin A is a prominent autocrine regulator of hepatocyte growth arrest. Hepatol Commun 2017; 1: 852-870. (PMID: 29404498)
- Pradhan-Sundd T, Zhou L, Vats R, Jiang A, Molina L, Singh S, Poddar M, Russell JM, Stolz DB, Oertel M, Apte U, Watkins S, Ranganathan S, Nejak-Bowen KN, Sundd P, Monga SP. Dual catenin loss in murine liver causes tight junctional deregulation and progressive intrahepatic cholestasis. Hepatology 2018; 67: 2320-2337. (PMID: 29023813)
- Russell JM, Lu W, Okabe H, Abrams MT, Oertel M, Poddar M, Singh S, Forbes SJ, Monga SP. Hepatocyte-specific ?-catenin deletion during severe liver injury provokes cholangiocytes to differentiate into hepatocytes. Hepatology 2019; 69: 742-759. (PMID: 30215850)
- Adebayo Michael AO, Ko S, Tao J, Moghe A, Yang H, Xu M, Russell JO, Pradhan-Sundd T, Liu S, Singh S, Poddar M, Monga JS, Liu P, Oertel M, Ranganathan S, Singhi A, Rebouissou S, Zucman-Rossi J, Ribback S, Calvisi D, Qvartskhava N, Görg B, Häussinger D, Chen X, Monga SP. Inhibiting glutamine-dependent mTORC1 activation ameliorates liver cancers driven by ?-catenin mutations. Cell Metab 2019; 29: 1135-1150. (PMID: 30713111)
- Wilkinson P, Alencastro F, Delgado E, Leek M, Weirich M, Otero A, Roy N, Brown W, Oertel M, Duncan A. Polyploid Hepatocytes Facilitate Adaptation and Regeneration to Chronic Liver Injury. AJP 2019; 189: 1241-1255. (PMID: 30928253)
- Yovchev MI, Lee EJ, Rodriguez-Silva W, Locker J, Oertel M. Biliary obstruction promotes multilineage differentiation of hepatic stem cells. Hepatol Commun 2019; 3: 1137-1150. (PMID: 31388633)
- Zhang R, Nakao T, Luo J, Xue Y, Cornuet P, Oertel M, Kosar K, Singh S, Nejak-Bowen K. Activation of Wnt/beta-catenin signaling and regulation of the farnesoid X receptor/beta-catenin complex after murine bile duct ligation. Hepatol Commun 2019; 3: 1642-1655. (PMID: 31832572)