A5071102862- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Liver Disease Diagnosis and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Renal Transplantation Outcomes and Treatments
- Organ Donation and Transplantation
- Pancreatic and Hepatic Oncology Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Liver physiology and pathology
- Pancreatitis Pathology and Treatment
- interferon and immune responses
- Gallbladder and Bile Duct Disorders
- Liver Diseases and Immunity
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Transplantation: Methods and Outcomes
- Systemic Lupus Erythematosus Research
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Renal cell carcinoma treatment
- Neuroendocrine Tumor Research Advances
- Immunotherapy and Immune Responses
- Abdominal vascular conditions and treatments
University Health Network
2016-2025
Toronto General Hospital
2016-2025
University of Toronto
2016-2025
Toronto General Hospital Research Institute
2018-2023
Health Net
2008-2023
Canada Research Chairs
2023
University of New Brunswick
2023
Princess Margaret Cancer Centre
2013-2019
Chinese Academy of Medical Sciences & Peking Union Medical College
2013-2015
Peking Union Medical College Hospital
2013
The liver is the largest solid organ in body and critical for metabolic immune functions. However, little known about cells that make up human its microenvironment. Here we report a map of cellular landscape using single-cell RNA sequencing. We provide transcriptional profiles 8444 parenchymal non-parenchymal obtained from fractionation fresh hepatic tissue five livers. Using gene expression patterns, flow cytometry, immunohistochemical examinations, identify 20 discrete cell populations...
Despite evidence that the intestinal microbiota (IM) is involved in pathogenesis of obesity, IM composition patients with nonalcoholic fatty liver disease (NAFLD) has not been well characterized. This prospective, cross-sectional study was aimed at identifying differences between adults biopsy-proven NAFLD (simple steatosis [SS] or steatohepatitis [NASH]) and living donors as healthy controls (HC). Fifty subjects were included: 11 SS, 22 NASH, 17 HC. One stool sample collected from each...
Background & Aims Non-alcoholic fatty liver disease (NAFLD) is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM) and bile acids (BA) suggest that dysbiosis may be accompanied an altered acid homeostasis, which in turn can contribute to the metabolic dysregulation seen NAFLD. This study sought examine BA homeostasis patients with NAFLD relate IM data. Methods was a prospective, cross-sectional of adults biopsy-confirmed (non-alcoholic liver: NAFL or...
The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead relying these factors, we used poor differentiation cancer-related symptoms to exclude patients likely have advanced HCC aggressive biology. We initially reported similar 5-year survival for whose tumors exceeded (M+ group) were within (M the Milan criteria. Herein, validate our original data a new prospective cohort report long-term follow-up (10-years) using an...
Liberal acceptance criteria are used when offering liver transplantation (LTx) for treatment of hepatocellular carcinoma (HCC) at our center. This provides a unique opportunity to assess outcomes in large North American series patients with advanced tumors.We hypothesized that acceptable survival rates can be achieved LTx any size or number HCC provided (a) imaging studies ruled out vascular invasion; (b) the was confined liver; and (c) not poorly differentiated on biopsy.Survival, based...
In nonalcoholic fatty liver disease, hepatic gene expression and acid (FA) composition have been reported independently, but a comprehensive profiling in relation to FA is lacking. The aim was assess this relationship. cross-sectional study, (Illumina Microarray) first compared among 20 patients with simple steatosis (SS), 19 steatohepatitis (NASH), 24 healthy controls. total lipids between SS NASH, associations FAs were examined. Gene differed mainly controls (SS NASH), including genes...
A significant challenge to delivering therapeutic doses of nanoparticles targeted disease sites is the fact that most become trapped in liver. Liver-resident macrophages, or Kupffer cells, are key cells hepatic sequestration nanoparticles. However, precise role macrophage phenotype plays nanoparticle uptake unknown. Here, we show human modulates hard uptake. Using gold nanoparticles, examined by monocyte-derived macrophages had been driven a "regulatory" M2 an "inflammatory" M1 and found...
The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for transplantation (LT) uses gelofusine, non–US Food and Drug Administration–approved, bovine‐derived, gelatin‐based solution. We report safety feasibility clinical NEVLP with human albumin–based Steen Transplant outcomes of 10 grafts that were perfused on the Metra device at 37 °C solution, plus 3 units erythrocytes compared matched historical control group 30 using cold storage (CS)...
The critical functions of the human liver are coordinated through interactions hepatic parenchymal and non-parenchymal cells. Recent advances in single-cell transcriptional approaches have enabled an examination with unprecedented resolution. However, dissociation-related cell perturbation can limit ability to fully capture liver's fraction, which limits comprehensively profile this organ. Here, we report landscape 73,295 cells from using matched RNA sequencing (scRNA-seq) single-nucleus...
Colorectal cancer is a leading cause of cancer-related death, and nearly 70% patients with this have unresectable colorectal liver metastases (CRLMs). Compared chemotherapy, transplant has been reported to improve survival in CRLMs, but North America, allograft shortages make the use deceased-donor allografts for indication problematic.To examine outcomes living-donor (LDLT) unresectable, liver-confined CRLMs.This prospective cohort study included at 3 American centers established LDLT...
Accumulation of activated immune cells results in nonspecific hepatocyte killing chronic hepatitis B (CHB), leading to fibrosis and cirrhosis. This study aims understand the underlying mechanisms humans define whether these are driven by widespread activation or a subpopulation cells. We enrolled CHB patients with active liver damage receive antiviral therapy performed longitudinal sampling using fine-needle aspiration investigate pathogenesis human liver. Single-cell sequencing total...
•ScRNA-seq revealed additional macrophage diversity in the NDD (healthy) liver.•CD206+ macrophages PSC liver show reduced responsiveness to stimulation.•CK7+ HNF4A+ transitioning hepatocytes are enriched fibrotic lesions comparison PBC and NDD. BackgroundPrimary sclerosing cholangitis (PSC) is an immune-mediated cholestatic disease characterized by bile retention, biliary tree destruction, progressive fibrosis leading end stage transplantation. There unmet need understand cellular...
Biliary strictures remain the most challenging aspect of adult right lobe living donor liver transplantation (RLDLT). Between 04/2000 and 10/2005, 130 consecutive RLDLTs were performed in our center followed prospectively. Median follow-up was 23 months (range 3-67) 1-year graft patient survival 85% 87%, respectively. Overall incidence biliary leaks (n = 19) or 22) 32% (41/128) 33 patients (26%). A duct-to-duct (D-D) Roux-en-Y (R-Y) anastomosis equally 64 each) with no difference stricture...
ABSTRACT Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease which has been difficult to study and treat because of the lack readily available animal model. Intranasal infection A/J mice with coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features SARS. All MHV-1-infected developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, hyaline membranes, resulting in death all animals. In...