Professor Xu, Aimin 徐愛民
Aimin Xu is currently a Professor jointly appointed by the Department of Medicine and the Department of Pharmacology & Pharmacy, and also the director for State Key Laboratory of Pharmaceutical Biotechnology (www.sklpb.hku.hk) at the University of Hong Kong. He received his BS (Hons) in medicine at Anhui Medical University in China in 1989 and his PhD in Biochemistry and Molecular Biology at the University of Auckland in New Zealand in 1999. He received his postdoctoral training at the School of Biological Sciences at the University of Auckland working on the proteomic identification of novel adipocyte-derived factors involved in obesity and insulin resistance.
Obesity is a major risk factor of type 2 diabetes (T2DM), insulin resistance and cardiovascular diseases (CVDs). In obesity, chronic metabolic stresses trigger adipose tissue inflammation and promote macrophage infiltration, resulting in aberrant secretion of bioactive peptides (known as adipokines). Our primary research interest is to investigate the role of adipokines in the pathogenesis of obesity-related insulin resistance, systemic inflammation, T2DM and vascular dysfunctions in animal models and human subjects. Our long-term goal is to develop adipokine-based diagnostic and therapeutic strategies for obesity-related cardio-metabolic complications. Our ongoing research projects include:
Identification and functional characterization of adipokine netowork: Using an integrated proteomics-based approach, we have identified multiple posttranslationally modified isoforms of adiponectin, and have demonstrated that hydroxylation and subsequent glycosylation of several lysine residues at the collagenous domain are obligatory for insulin-sensitizing effects of adiponectin by promoting the formation of high molecular weight oligomeric complexes (Wang Y, JBC, 2002, 2005, 2006; Biohcem. J, 2008; Xu A, JCI, 2003). We have also identified the circulating form of adipocyte fatty acid-binding protein (A-FABP) and lipocalin-2 as pro-inflammatory adipokines mediating toxic lipids-induced insulin resistance and vascular dysfunction (Xu A, Clin Chem: 2006; Circulation: 2007; Hui X, JBC:2010). More recently, we have demonstrated that fibroblast growth factor (FGF21), an anti-diabetic hormone traditionally thought to be produced from hepatocytes, is also secreted from adipose tissues (Zhang X, Diabetes, 2008 and Lin Z, Cell Metabolism, 2013). Furthermore, we found that adipose-derived FGF21 exerts its anti-diabetic activities by inducing adiponectin production. (Fig 1) Currently, we are investigating the mechanisms by which FGF21 controls adiponectin production under physiological and pathological conditions.
Signaling mechanisms underlying the insulin-sensitizing and vascular protective effects of adiponectin: Adiponectin is one of the few adipokines with insulin-sensitizing and cardiovascular protective properties, but its mechanisms of actions remain poorly characterized. In 2007, We identified APPL1, an intracellular adaptor protein, as a key signaling molecule that bind to adiponectin receptors mediating adiponectin-induced activation of AMP-activated protein kinase (AMPK), thereby inducing eNOS activation and NO production in endothelial cells (Cheng KK, Diabetes, 2007). Our subsequent studies demonstrated that APPL1 is also a key component of insulin-evoked signaling cascade, by promoting membrane targeting and translocation of the protein kinase Akt (Cheng KK, Cell Metab. 2009; BJ, 2013). Furthermore, using APPL1 transgenic and knockout mice, we have found that APPL1 plays a central role in controlling vascular homeostasis as well as insulin secretion (Cheng KK, PNAS, 2012; Wang Y, Diabetes, 2011). We have also uncovered an important role of adiponectin in preventing diabetes-induced vascular injury, by promoting the functions of endothelial progenitor cells (EPCs) via an AMPK-dependent mechanism (Chang J, Diabetes, 2010). In light of the key role of AMPK in mediating the endothelium-protective effects of adiponectin, we have generated transgenic mice with endothelium-selective constitutive AMPK activation, and found that endothelium-selective activation of AMPK is sufficient to prevent diabetes-associated impairment of vascular repair via induction of heme oxygenase-1 (HO1) pathway, which in turn augments EPCs-mediated endothelial regeneration (Li Y, Circulation, 2012). (Fig 2) We are currently investigating the roles of FGF21/adiponectin axis in protecting obesity-induced vascular inflammation and atherosclerosis in both rodents and large animals.
Translational research: Adipokines-based assay development, clinical diagnosis and drug discovery: Through the Antibody and Immunoassay Service (AIS, www.antibody.hku.hk), we have developed over 20 highly specific immunoassay kits for new adipokines and other biomarkers related to cardio-metabolic diseases. These assay kits are now being commercialized for basic and clinical research, clinical diagnosis and high throughput drug screening. We are working with several overseas and Mainland hospitals to conduct long-term prospective studies to validate the clinical values of our several adipokine assays for risk prediction and early diagnosis of cardiovascular complications of diabetes in different ethnic groups. In addition, we are now using these adipokines as biomarkers for high throughput screening of new compounds from medicinal herbs with anti-diabetic and vasculo-protective properties and for discovery of drug candidates for obesity-related medical complications by targeting the adipo-vascular axis.
|Awardees||Award Date||Honours / Awards / Prizes||Category|
|2011-11-01||Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation: The 18th Hong Kong International Cancer Conference||Research Achievement|
|2006-01-01||Best Oral Presentation Award: 11th Medical Research Conference 2006||Research Achievement|
|2013-01-01||Best Oral Presnetation Award: Research Centre Of Heart, Brain, Hormone & Healthy Aging, University of Hong Kong||Research Achievement|
|2006-12-01||Outstanding Young Researcher Awards: The University of Hong Kong||Research Achievement|
|2012-12-01||Best Oral Presentation Award: 7th International HuaXia Congress of Endocrinology||Research Achievement|
|2010-03-01||Outstanding Abstract Prize, Fifth International Symposium On Healthy Aging: Is Aging A Disease?: Research Centre Of Heart, Brain, Hormone & Healthy Aging, University of Hong Kong||Research Achievement|
|2012-02-01||Best Abstract in Basic Science and Translational Medicine: 17th Medical Research Conference||Research Achievement|
|2014-01-01||Best Abstract in Basic Science and Translational (Oral Presentation): 19th Medical Research Conference||Research Achievement|
|2014-03-01||FGF21 as a novel metabolic regulator: from bench to bed: 2014中国糖尿病转化医学论坛， 厦门||Others|
|2010-08-01||Outstanding Scientific Work – Winning poster presentation: Frontiers in Cardiovascular Biology; European Society of Cardiology||Research Achievement|
|2016-07-01||2016 Research Output Award: The University of Hong Kong||Research Achievement|
|2014-01-01||Best Abstract in Basic Science and translational (Oral Presentation): 19th Medical Research Conference||Research Achievement|
|2015-02-01||Research Travel Scholarship 2015: American Academy of Neruology||Research Achievement|
|2015-11-01||Basic Science Award, 35th Hong Kong Orthopaedic Association Annual Congress: Hong Kong Orthopaedic Association||Research Achievement|
|2016-04-01||Croucher Senior Researcher fellowship award: Croucher Foundation||Research Achievement|
|Term Period||Position||Professional Societies|
|02/2012 to present||Panel member||Hong Kong Research grant Council|
|07/2011-present||External Reviewer||Diabetes Australia|
|05/2011||External Reviwer||RGC GRF|
|06/2013||External review||UK MRC grant|
|03/2010 and 07/2015||External Reviewer for Diabetes UK research grants||Diabetes UK|
|10/2010; 10/2013||External Reviewer||New Zealand Health Research Council|
|03/2012||External Reviewer||Wellcome Trust|
|05/2015||eXTERNAL Reviewer||German Academic Exchange Service (DAAD)|
|05/2015||EXTERNAL REVIEWER||Australia NHMRC|
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