Biosketch / Results /
Edwin ChanClinical Assistant Professor, Department of Medicine
Education— Queen's University, Canada, Clinical Fellowships
— University of Dundee, Scotland, Internship
— Queen's University, Canada, Residency Training
1990 — University of Dundee, Scotland, Medical Education
Research SummaryLiver fibrosis, or cirrhosis in its end stage form, is one of the most devastating complications of alcohol consumption and is responsible for much of the morbidity and mortality in the western world, whether due to alcohol abuse, liver infections, drugs or chemical toxins. Our interest in hepatic fibrosis stems from pioneering work by Bruce Cronstein who first demonstrated that the purine nucleoside, adenosine, is a potent antiinflammatory agent, and mediates much of the antiinflammatory effects of methotrexate and other medications commonly used in the treatment of rheumatoid arthritis and other inflammatory diseases. Since liver fibrosis is also one of the most severe of complications observed in patients treated with methotrexate, and adenosinergic agents promote ground matrix production in wounds, we postulated that the released adenosine may be responsible for the development of hepatic fibrosis in methotrexate-treated patients.
Our prior observations show that both methotrexate and ethanol induce the release of adenosine from liver cells, which in turn acts on a specific cell surface receptor, the A2A receptor, on hepatic stellate cells to promote collagen synthesis. These in vitro observations are supported by the in vivo demonstration that mice rendered genetically deficient for the adenosine A2A receptor are protected against liver fibrosis in a widely accepted chemical model, induction by carbon tetrachloride.
The importance of adenosine and its receptors in their mediation of liver cirrhosis is only just beginning to be appreciated. Ongoing studies in our laboratory examine the influence of adenosine on collagen formation vs. breakdown, intracellular mechanisms involved in signaling an increase in collagen production (cyclic AMP/protein kinase A pathway and mitogen-activated protein kinase pathway), and further animal models of toxin-induced hepatic fibrosis. We believe that elucidation of the molecular pathways of hepatic fibrogenesis will lead to potential therapeutic targets for cirrhosis, a disease for which there is presently no cure, and our encouraging preliminary results lead us to believe that this is an achievable goal.
Research InterestsMolecular Regulation of Fibrogenesis
Differences in psychiatric symptoms among Asian patients with depression: a multi-country cross-sectional study
Sulaiman, Ahmad H; Bautista, Dianne; Liu, Chia-Yih; Udomratn, Pichet; Bae, Jae Nam; Fang, Yiru; Chua, Hong C; Liu, Shen-Ing; George, Tom; Chan, Edwin; Tian-mei, Si; Hong, Jin Pyo; Srisurapanont, Manit; Rush, A John. Differences in psychiatric symptoms among Asian patients with depression: a multi-country cross-sectional study. Psychiatry & clinical neurosciences. 2014 Apr ;68(4):245-254 (992402)
Mechanisms of action of methotrexate
Chan, Edwin S L; Cronstein, Bruce N. Mechanisms of action of methotrexate. Bulletin of the Hospital for Joint Diseases (2013). 2013 ;71 Suppl 1:S5-S8 (761472)
Extracellular Generation of Adenosine by the Ectonucleotidases CD39 and CD73 Promotes Dermal Fibrosis
Fernandez, Patricia; Perez-Aso, Miguel; Smith, Gideon; Wilder, Tuere; Trzaska, Sean; Chiriboga, Luis; Franks, Andrew Jr; Robson, Simon C; Cronstein, Bruce N; Chan, Edwin S L. Extracellular Generation of Adenosine by the Ectonucleotidases CD39 and CD73 Promotes Dermal Fibrosis. American journal of pathology. 2013 Dec ;183(6):1740-1746 (652432)
Adenosine 2A Receptor Promotes Collagen Production By Human Fibroblasts Via Smad2/3-Independent Pathways Involving Cyclic AMP and AKT
Perez-Aso, Miguel ; Fernandez, Patricia ; Mediero, Aranzazu ; Chan, Edwin S. L. ; Cronstein, Bruce N.. Adenosine 2A Receptor Promotes Collagen Production By Human Fibroblasts Via Smad2/3-Independent Pathways Involving Cyclic AMP and AKT [Meeting Abstract]. Arthritis & rheumatism. 2013 OCT;65 10 10(SI):S790-S790 (657292)
Adenosine 2A receptor promotes collagen production by human fibroblasts via pathways involving cyclic AMP and AKT but independent of Smad2/3
Perez-Aso, Miguel; Fernandez, Patricia; Mediero, Aranzazu; Chan, Edwin S; Cronstein, Bruce N. Adenosine 2A receptor promotes collagen production by human fibroblasts via pathways involving cyclic AMP and AKT but independent of Smad2/3. FASEB journal. 2013 Nov 7;28(2):802-812 (761482)