A5044621022- Liver physiology and pathology
- Hepatocellular Carcinoma Treatment and Prognosis
- Liver Disease Diagnosis and Treatment
- Organ Transplantation Techniques and Outcomes
- Congenital Diaphragmatic Hernia Studies
- Pancreatic and Hepatic Oncology Research
- Congenital Heart Disease Studies
- PI3K/AKT/mTOR signaling in cancer
- Liver Disease and Transplantation
- Pediatric Hepatobiliary Diseases and Treatments
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Pancreatic function and diabetes
- Cancer Mechanisms and Therapy
- Congenital Anomalies and Fetal Surgery
- Fibroblast Growth Factor Research
- Neonatal Respiratory Health Research
- Heat shock proteins research
- Microtubule and mitosis dynamics
- Sarcoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Mechanical Circulatory Support Devices
- Cytokine Signaling Pathways and Interactions
- Prostate Cancer Treatment and Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
University of Washington
2016-2025
Seattle Children's Hospital
2007-2024
Seattle University
2019-2023
Center Point
2022
University of Michigan
2021
University of Iowa
2020
University of Washington Medical Center
2019
Medical University of South Carolina
2015
In contrast to mammals, lower vertebrates have a remarkable capacity regenerate complex structures damaged by injury or disease. This process, termed epimorphic regeneration, involves progenitor cells created through the reprogramming of differentiated activation resident stem cells. Wnt/beta-catenin signaling regulates cell fate and proliferation during embryonic development function in adults, but its functional involvement regeneration has not been addressed. Using transgenic fish lines,...
The unique ability of the liver to regenerate itself has fascinated biologists for years and made it prototype mammalian organ regeneration. Harnessing this process great potential benefit in treatment failure been focus intense research over past 50 years. Not only will detailed understanding cell proliferation response injury be applicable other dysfunction organs, may also shed light on how cancer develops a cirrhotic liver, which there is pressure cells regenerate. Advances molecular...
Little is known about the differentiation capabilities of nonhematopoietic cells human fetal liver. We report isolation and characterization a liver multipotent progenitor cell (hFLMPC) population capable differentiating into mesenchymal lineages. Human livers (74-108 days gestation) were dissociated maintained in culture. treated colonies with geneticin mechanically isolated hFLMPCs, which kept an undifferentiated state by culturing on feeder layers. derived daughter serial dilution,...
In this 'Snapshot' article, we take a fresh look at the fundamentals of liver regeneration in light recent technical innovations. While mammalian response to partial hepatectomy (PH) has been studied for decades [1Fausto N. Campbell J.S. Riehle K.J. Liver regeneration.Hepatology. 2006; 43: S45-S53Crossref PubMed Scopus (1253) Google Scholar, 2Michalopoulos G.K. after hepatectomy.Am J Pathol. 2010; 176: 2-13Abstract Full Text PDF (548) Scholar], years use new experimental techniques not only...
Suppressor of cytokine signaling 3 (SOCS3) down-regulates several pathways in multiple cell types, and previous data suggest that SOCS3 may shut off activation at the early stages liver regeneration (Campbell, J.S., L. Prichard, F. Schaper, J. Schmitz, A. Stephenson-Famy, M.E. Rosenfeld, G.M. Argast, P.C. Heinrich, N. Fausto. 2001.J. Clin. Invest. 107:1285–1292). We developed Socs3 hepatocyte-specific knockout (Socs3 h-KO) mice to directly study role during after a two-thirds partial...
Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. Yet, their downstream oncogenic signaling mechanisms poorly understood. We used global phosphoproteomics and activity profiling to map conserved outputs driven by a range of genetic changes PKA human cancer. Two networks were identified PKA: RAS/MAPK components an Aurora Kinase (AURKA)/glycogen synthase (GSK3) sub-network with toward MYC oncoproteins. Findings validated two PKA-dependent cancer models:...
Fibrolamellar carcinoma (FLC) is a rare liver cancer. FLCs uniquely produce DNAJ-PKAc, chimeric enzyme consisting of chaperonin-binding domain fused to the Cα subunit protein kinase A. Biochemical analyses clinical samples reveal that unique property this fusion ability recruit heat shock 70 (Hsp70). This cellular chaperonin frequently up-regulated in cancers. Gene-editing mouse hepatocytes generated disease-relevant AML12DNAJ-PKAc cell lines. Further indicate proto-oncogene A-kinase...
Abstract TNF and IL-6 are considered to be important the initiation or priming phase of liver regeneration. However, signaling pathways that lead production these cytokines after partial hepatectomy (PH) have not been identified. Enteric-derived LPS appears regeneration, possibly by stimulating proinflammatory cytokine surgery. To determine whether involved in regulation during we performed PH on mice lacking TLRs Tlr4 Tlr2, coreceptor, Cd14, Myd88, an adapter protein most TLR IL-1R...
Chronic liver injury leads to fibrosis, cirrhosis, and loss of function. Liver cirrhosis is the 12th leading cause death in United States, it primary risk factor for developing cancer. Fibrosis result from activation hepatic stellate cells (HSCs), which are collagen producing cell type liver. Here, we show that platelet-derived growth receptor α (PDGFRα) expressed by human HSCs, PDGFRα expression elevated disease. Using a green fluorescent protein (GFP) reporter mouse strain, evaluated role...
The tumor microenvironment (TME) is critical to every aspect of cancer biology. Organotypic slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but association between clinicopathologic parameters vitro TSC behavior has not been well-defined.One hundred eight fresh specimens from liver resections at a tertiary academic center were procured precisely cut with Vibratome create 250 μm × 6 mm slices. These fixed-dimension TSCs grown on...
Cirrhosis is the primary risk factor for development of hepatocellular carcinoma (HCC), yet mechanisms by which cirrhosis predisposes to carcinogenesis are poorly understood. Using a mouse model that recapitulates many aspects pathophysiology human liver disease, we explored changes in microenvironment induce dysplasia and HCC. Hepatic expression platelet-derived growth C (PDGF-C) induces progressive fibrosis, chronic inflammation, neoangiogenesis sinusoidal congestion, as well global gene...
Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little known about immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed characterize FLC microenvironment adjacent non-tumor (NTL). Flow cytometry T cell receptor (TCR) sequencing determine phenotype tumor-infiltrating cells extent clonal expansion. Fresh human slice cultures...
Background Fibrolamellar carcinoma (FLC), a rare and fatal liver cancer lacking effective drug therapy, is driven by the DNAJ-PKAc fusion oncoprotein. However, underlying mechanism of DNAJ-PKAc’s role in FLC tumour growth remains enigmatic. Objective We sought to determine protein kinase-mediated signalling networks that drive proliferation FLC. Design integrated combination newly established preclinical models an unbiased polypharmacology-based approach identify downstream kinases involved...
Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim this study was to define current management strategies and outcomes these patients using multi-institutional dataset curated by Pediatric Surgical Oncology Research Collaborative.
Partial hepatectomy (PH) consistently results in an early increase of circulating interleukin-6 (IL-6), which is thought to play a major role liver regeneration. Activation this cytokine after PH requires the adaptor protein, MyD88, but specific MyD88-related receptors involved remain unidentified. It also unknown whether magnitude IL-6 elevation determines extent subsequent hepatocyte proliferation. Here, we uncovered artifacts assessment levels when using cardiac puncture mice PH. By...