Education
- Medical University Lübeck, Germany, 10/1989 - 07/1995
- Harvard Medical School, Boston, MA 08/1995 - 04/1996
- University of Münster, Germany, 05/1996 - 12/1996
- University of Münster, Germany, Department of Pediatrics, Medical Intern, 02/1997 - 07/1998
- University of Münster, Germany, Department of Pediatrics, Medical Resident, 08/1998 - 09/2001
- Oregon Health & Science University, Portland, Oregon, Department of Molecular and Medical Genetics, 10/2001 -10/2005
In the News
Grants and Funding
- Next-generation human liver gene therapy | NIH | 2021-09-30 - 2026-06-30 | Role: Principal Investigator
- Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus | NIH | 2018-09-20 - 2023-07-31 | Role: Co-Principal Investigator
- Targeting AAV vectors to cell types involved in alcohol-induced liver injury | NIH | 2018-09-01 - 2023-05-31 | Role: Principal Investigator
- Building a functional biliary system from hepatocytes | NIH | 2016-09-01 - 2021-07-31 | Role: Co-Principal Investigator
- Microphysiological systems to interrogate the Islet-Liver-Adipose Axis in normal physiology and Type-2 Diabetes Mellitus | NIH | 2018-09-20 - 2020-07-31 | Role: Co-Principal Investigator
- Myofibroblast-to-hepatocyte conversion as a therapy for alcoholic liver disease | NIH | 2013-09-01 - 2016-08-31 | Role: Principal Investigator
- Liver regeneration with stems cells of uniparental origin | NIH | 2008-04-01 - 2013-08-31 | Role: Co-Principal Investigator
Research Narrative
Our research is aimed at developing new therapies for patients with severe liver diseases. To restore liver function in patients with liver failure, we are working on generating hepatocytes from human pluripotent stem cells or by reprogramming of readily accessible human cell types. To be therapeutically effective, these cells need to replicate both function and the ability to proliferate of primary human hepatocytes. To establish and improve protocols for the production of such cells, we have been working on obtaining a detailed molecular understanding of hepatocyte differentiation and regeneration. For this, we are using mouse models for liver cell lineage tracing developed in our laboratory. In addition, we are using rigorous animal models of human liver failure to test the therapeutic efficacy of our surrogate hepatocytes. While developing novel liver cell therapies is our main focus, we are also using hepatocytes derived from human pluripotent stem cells or by reprogramming to generate in vitro and in vivo liver disease models. Another goal of our laboratory is to determine the origin and follow the fate of liver cancer-initiating cells with the goal to identify the molecular mechanisms that drive liver cancer formation and progression. For this, we are using new mouse models generated in our laboratory. By obtaining an improved understanding of hepatocarcinogenesis, we hope to contribute to the development of strategies for early detection and effective eradication of liver cancer.
Research Interests
Liver Regeneration
Liver Cell Therapy
LIver Development
Research Pathways
Publications
- Human Hepatocytes Can Give Rise to Intrahepatic Cholangiocarcinomas.| | View in PubMed
- Modeling and therapeutic targeting of inflammation-induced hepatic insulin resistance using human iPSC-derived hepatocytes and macrophages.| | View in PubMed
- Human iPSC-Derived Proinflammatory Macrophages cause Insulin Resistance in an Isogenic White Adipose Tissue Microphysiological System.| | View in PubMed
- Reply.| | View in PubMed
- Aquaporin 9 induction in human iPSC-derived hepatocytes facilitates modeling of ornithine transcarbamylase deficiency.| | View in PubMed
- Integrated Isogenic Human Induced Pluripotent Stem Cell-Based Liver and Heart Microphysiological Systems Predict Unsafe Drug-Drug Interaction.| | View in PubMed
- Induced Pluripotent Stem Cell-derived Hepatocytes From Patients With Nonalcoholic Fatty Liver Disease Display a Disease-specific Gene Expression Profile.| | View in PubMed
- Emerging cell therapy for biliary diseases.| | View in PubMed
- Transcriptomic Traces of Adult Human Liver Progenitor Cells.| | View in PubMed
- Broad Distribution of Hepatocyte Proliferation in Liver Homeostasis and Regeneration.| | View in PubMed
- Hepatocyte Nuclear Factor 4 Alpha Activation Is Essential for Termination of Liver Regeneration in Mice.| | View in PubMed
- De novo formation of the biliary system by TGFβ-mediated hepatocyte transdifferentiation.| | View in PubMed
- Postnatal Organogenesis by Transdifferentiation.| | View in PubMed
- Advances in cholangiocarcinoma research: report from the third Cholangiocarcinoma Foundation Annual Conference.| | View in PubMed
- In Vivo Hepatic Reprogramming of Myofibroblasts with AAV Vectors as a Therapeutic Strategy for Liver Fibrosis.| | View in PubMed
- Assessing the therapeutic potential of lab-made hepatocytes.| | View in PubMed
- Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.| | View in PubMed
- A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver.| | View in PubMed
- AAV8-mediated in vivo overexpression of miR-155 enhances the protective capacity of genetically attenuated malarial parasites.| | View in PubMed
- Evidence against a Stem Cell Origin of New Hepatocytes in a Common Mouse Model of Chronic Liver Injury.| | View in PubMed
- Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury.| | View in PubMed
- Brief report: Parthenogenetic embryonic stem cells are an effective cell source for therapeutic liver repopulation.| | View in PubMed
- Failure to achieve normal metabolic response in non-obese diabetic mice and streptozotocin-induced diabetic mice after transplantation of primary murine hepatocytes electroporated with the human proinsulin gene (p3MTChins).| | View in PubMed
- Inhibition of microRNA-24 expression in liver prevents hepatic lipid accumulation and hyperlipidemia.| | View in PubMed
- Mouse liver repopulation with hepatocytes generated from human fibroblasts.| | View in PubMed
- Addendum: A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice.| | View in PubMed
- Human induced pluripotent stem cell-based microphysiological tissue models of myocardium and liver for drug development.| | View in PubMed
- MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer.| | View in PubMed
- Transplantable liver organoids made from only three ingredients.| | View in PubMed
- Highly efficient differentiation of functional hepatocytes from human induced pluripotent stem cells.| | View in PubMed
- A therapy for liver failure found in the JNK yard.| | View in PubMed
- Akt/Notch activation drives rapid cholangiocarcinoma development originating from mature hepatocytes in the mouse.| | View in PubMed
- Cholangiocarcinomas can originate from hepatocytes in mice.| | View in PubMed
- A ZFN/piggyBac step closer to autologous liver cell therapy.| | View in PubMed
- A microRNA-21 surge facilitates rapid cyclin D1 translation and cell cycle progression in mouse liver regeneration.| | View in PubMed
- Stem cells in liver diseases and cancer: recent advances on the path to new therapies.| | View in PubMed
- Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration.| | View in PubMed
- A simple code for installing hepatocyte function.| | View in PubMed
- Mouse chimeras as a system to investigate development, cell and tissue function, disease mechanisms and organ regeneration.| | View in PubMed
- Core promoter recognition complex changes accompany liver development.| | View in PubMed
- The MAP3K TAK1: a chock block to liver cancer formation.| | View in PubMed
- Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice.| | View in PubMed
- Transplanted nonviable human hepatocytes produce appreciable serum albumin levels in mice.| | View in PubMed
- miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues.| | View in PubMed
- Therapeutic liver reconstitution with murine cells isolated long after death.| | View in PubMed
- MicroRNAs control hepatocyte proliferation during liver regeneration.| | View in PubMed
- Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis.| | View in PubMed
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- A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice.| | View in PubMed
- On the origin of the term "stem cell".| | View in PubMed
- Myeloid lineage progenitors give rise to vascular endothelium.| | View in PubMed
- Bone marrow-derived cells fuse with normal and transformed intestinal stem cells.| | View in PubMed
- Sustained phosphorylation of Bid is a marker for resistance to Fas-induced apoptosis during chronic liver diseases.| | View in PubMed
- Myeloid Lineage-Restricted Progenitors Contribute to Vascular Endothelium.| | View in PubMed
- In vivo genetic selection of renal proximal tubules.| | View in PubMed
- Therapeutic cell fusion.| | View in PubMed
- Delineating the hepatocyte's hematopoietic fusion partner.| | View in PubMed
- Myelomonocytic cells are sufficient for therapeutic cell fusion in liver.| | View in PubMed
- Embryonic versus adult stem cell pluripotency: in liver only fusion matters.| | View in PubMed
- Cell fusion is the principal source of bone-marrow-derived hepatocytes.| | View in PubMed
- Argininosuccinate lyase (ASL) deficiency: mutation analysis in 27 patients and a completed structure of the human ASL gene.| | View in PubMed
- Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene.| | View in PubMed
- Telomerase activity distinguishes between neuroblastomas with good and poor prognosis.| | View in PubMed
- Telomerase activity in human proliferative breast lesions.| | View in PubMed
- Nonisotopic single strand conformation analysis of the 5 alpha-reductase type 2 gene for the diagnosis of 5 alpha-reductase deficiency.| | View in PubMed
- Molecular genetic analysis and human chorionic gonadotropin stimulation tests in the diagnosis of prepubertal patients with partial 5 alpha-reductase deficiency.| | View in PubMed