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A photo of Prof LAM Siu Ling, Karen
Prof LAM Siu Ling, Karen
Rosie TT Young Professor in Endocrinology and Metabolism
Chair Professor in Medicine
MBBS (Hon.) MRCP(UK) MD (HK), FRCP (Edin and Lond), FRACP, FHKCP, FHKAM (Medicine)
an email logo ksllam@hku.hk
a telephone logo 2255-3348
a fax logo 2816-2095

Biography

Professor Karen Lam is Chair Professor in Medicine, Director of the Research Centre of Heart, Brain, Hormone & Healthy Aging, Chairman of Clinical Trial Centre and Clinical Director of the State Key Laboratory of Pharmaceutical Biotechnology (focusing on diabetes and obesity), at the University of Hong Kong. The Founding President of Diabetes Hongkong, she was also a president of the HK Endocrine Society and Chairman of two specialty boards of the HK College of Physicians – Advanced Internal Medicine and Endocrinology, Diabetes & Metabolism.

Research Profile

Professor Lam has published extensively on clinical, basic and translational research in diabetes and endocrinology, including publications in Diabetes, Diabetes Care, JCEM, ATVB, Circulation, Cell Metabolism, PNAS, JCI and Lancet. Heading an integrated research team with strengths and platforms ranging from cell and animal based research to epidemiological, genetic and clinic-based studies, her current research focuses on the pathogenetic and therapeutic significance of adipokines in diabetes and other obesity-related cardiometabolic disorders. She leads the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS; 1995-2014), a population-based cohort study on cardiovascular (CV) risk factors and diseases with the longest follow-up in China, which serves to chart the rise in obesity and metabolic syndrome in Southern China, as well as providing the database and biobank for investigating the interaction of environmental and genetic factors underlying obesity, diabetes and CV diseases in Chinese. The above platforms, database and biobanks have allowed her team to identity novel biomarkers of cardiometabolic diseases and demonstrate their clinical significance, notable examples being the adipocyte fatty acid binding protein (A-FABP) and fibroblast growth factor 21 (FGF21), which have inspired numerous follow-up studies in the field, from the international community.

Her team was the first to demonstrate that serum levels of A-FABP, a proinflammatory adipokine associated with insulin resistance, are raised in obesity and predict the development of the metabolic syndrome and type 2 diabetes (T2DM) (Clin Chem 2006; Circulation 2007; Diabetes Care 2007). She and her collaborators have subsequently confirmed its clinical significance in diabetic nephropathy (Diabetes Care 2009), stroke (Neurology 2011) and other CV diseases (ATVB 2007; EHJ 2008; JAHA 2013), fatty liver diseases (Hepatology 2009), and obstructive sleep apnoea (ERJ 2009); elucidated its regulation by the C-Jun NH2-terminal kinase (JNK) inflammatory signaling (JBC 2010; Diabetes 2011), and demonstrated the effectiveness of a small molecule A-FABP inhibitor in treating fatty liver diseases (J Hepatol 2013). In addition, her study on a transgenic mouse with adipose tissue specific JNK inactivation (Diabetes 2011) highlighted the importance of JNK activation in linking adipose tissue inflammation, dysregulated adipokine secretion and insulin resistance in obesity. For FGF21, a hormone previously considered as largely a hepatokine, her paper in Diabetes 2008 provided the first evidence that the FGF21 expression in the adipocytes is markedly increased in obesity, leading to raised circulating FGF21 levels. She subsequently showed that high FGF21 levels could predict the development of T2DM (Diabetes Care 2011) and distinguish T2DM from autoimmune diabetes (JCEM 2012). As beneficial metabolic effects of FGF21 and its analog are observed in animals and humans, respectively, this paradoxical increase in FGF21 levels suggests that obesity is associated with FGF21 resistance. Her findings have been confirmed by numerous other groups. Subsequent studies conducted by her group and others have reported that elevated FGF21 levels are present in atherosclerosis (ATVB 2013), fatty liver and other obesity related disorders, and predicted the development of diabetic nephropathy (JCEM 2015). The underlying mechanisms of FGF21 resistance, which will impact on the therapeutic use of FGF21, have elucidated by her group (Diabetes 2013) and other researchers.  Her work on the genetics of obesity, diabetes and lipid metabolism including the first demonstration that obesity susceptibility gene variants identified from GWAS in Caucasians are also clinically relevant to Chinese (JCEM 2010; EJE 2011), and the discovery of novel coding sequence variants associated with lipid traits in Chinese (Nature Communications 2016), has led to invitations of international collaborations (Diabetologia 2012; Diabetes 2013, Asian Exome Chip Lipid Study 2016).

Selected Publications

  1. CS Tang, H Zhang, CYY Cheung, M Xu, JCY Ho, Wi Zhou, SS Cherny, Y Zhang, O Holmen, KW Au, H Yu, L Xu, J Jia,  RM Porsch, L Sun, W Xu, H Zheng, LY Wong, Y Mu, J Dou, CHY Fong, Su Wang, X Hung, L Dong, Y Liao, J Wang, LSM Lam, ML Yang, J Chen, CW Siu, G Xie, YC Woo, Y Wu, KCB Tan, K Hveem, BMY Cheung, S Zöllner,  A Xu, YE Chen, CQ Jiang, Y Zhang, TH Lam, S Ganesh, Y Huo, *PC Sham, *KSL Lam, *CJ Willer, *HF Tse, *W Gao. (co-supervising authors) Exome-wide Association Analysis Reveals Novel Coding Sequence Variants Associated with Lipid Traits in Chinese. Nat Commun 2015;6:10206 [IF:11.470] #citations on 16/05/2016: 3
  2. CH Lee, EYL Hui, YC Woo, CY Yeung, WS Chow, MAM Yuen, CHY Fong, A Xu, KSL Lam. Circulating fibroblast growth factor 21 levels predict progressive kidney disease in subjects with type 2 diabetes and normoalbuminuria. J Clin Endocrinol Metab 2015 Apr;100(4):1368-75  [IF:6.209] #citations on 16/05/2016: 3
  3. WS Chow, A Xu, YC Woo, AWK Tso, SC Cheung, CHY Fong, HF Tse, MT Chau, BMY Cheung, KSL Lam. Serum fibroblast growth factor-21 levels are associated with carotid atherosclerosis independent of established cardiovascular risk factors. Arterioscler Thromb Vasc Biol  2013;33(10):2454-9  [IF:6.338] #citations on 16/05/2016: 29
  4. RL Hoo, PC Lee, Mi Zhou, YL Wong, X Hui, A Xu, KSL Lam. Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice. J Hepatol 2013;58(2):358-64  [IF:9.858] #citations on 16/05/2016: 11
  5. Y Xiao, A Xu, LSC Law, C Chen, H Li, X Li, L Yang, S Liu, Z Zhou, KSL Lam. Distinct changes in serum fibroblast growth factor 21 level in different subtypes of diabetes. J Clin Endocr Metab 2012;97(1):E54-8  [IF:6.430] #citations on 16/05/2016: 31
  6. X Zhang, A Xu, SK Chung, JH Cresser, G Sweeney, RLC Wong, A Lin, KSL Lam. Selective inactivation of c-Jun NH2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice. Diabetes 2011;60(2):486-95  [IF:7.895] #citations on 16/05/2016: 50
  7. C Chen, BMY Cheung, AWK Tso, Y Wang, LS Law, KL Ong, NMS Wat, A Xu, KSL Lam. High plasma level of fibroblast growth factor 21 is an Independent predictor of type 2 diabetes: a 5.4-year population-based prospective study in Chinese subjects. Diabetes Care 2011;34(9):2113-5  [IF:7.735] #citations on 16/05/2016: 48
  8. AWK Tso, TKY Lam, A Xu, KH Yiu, HF Tse, LSW Li, LSC Law, BMY Cheung, RTF Cheung, KSL Lam. Serum adipocyte fatty acid-binding protein is associated with ischemic stroke and early death. Neurology 2011;76(23):1968-75  [IF:8.249] #citations on 16/05/2016: 20
  9. CYY Cheung, AWK Tso, BMY Cheung, A Xu, KL Ong, CHY Fong, NMS Wat, ED Janus, PC Sham, KSL Lam. Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a Chinese population. J Clin Endocrinol Metab 2010;95:1395-403  [IF:6.430]  #citations on 16/05/2016: 46
  10. DCY Yeung, A Xu, AWK Tso, WS Chow, NMS Wat, CHY Fong, S Tam, PC Sham, KSL Lam. Circulating levels of adipocyte and epidermal fatty acid-binding proteins in relation to nephropathy staging and macrovascular complications in type 2 diabetic patients. Diabetes Care 2009;32(1):132-4  [IF: 6.718]  #citations on 16/05/2016: 23
  11. XM Zhang, DCY Yeung, M Karpisek, D Stejskal, F Liu, RLC Wong, *KSL Lam, *A Xu. (*co-corresponding authors). Serum fibroblast growth factor-21 levels are increased in obesity and associate independently with the metabolic syndrome in humans. Diabetes 2008;57:1246-53  [IF:7.895] #citations on 16/05/2016: 287
  12. A Xu, AWK Tso, BMY Cheung, Y Wang, NMS Wat, CHY Fong, ED Janus, KSL Lam. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation 2007;115:1537-43  [IF:5.202] #citations on 16/05/2016: 197
  13. DCY Yeung, A Xu, SCW Cheung, NMS Wat, MH Yau, CHY Fong, MT Chau, KSL Lam. Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis. Arterioscler Thromb Vasc Biol 2007;27:1796-802  [IF:6.338] #citations on 16/05/2016: 105
  14. AWK Tso, A Xu, PC Sham, NMS Wat, Y Wang, CHY Fong, BMY Cheung, ED Janus, KSL Lam. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes - a 10-year prospective study in Chinese. Diabetes Care 2007:30:2667-72  [IF:7.735] #citations on 16/05/2016: 132
     

Key Offices

  1. Clinical Director, State Key Laboratory of Pharmaceutical Biotechnology
  2. Director, Research Centre of Heart, Brain, Hormone & Healthy Aging, HKU
  3. Chairman, Management Committee, Clinical Trial Centre, HKU
  4. Founding Director, KK Leung Diabetes Centre, Queen Mary Hospital
  5. Member, Research Assessment Exercise 2014 - Health Science Panel, University Grants Committee
  6. Founding President, Diabetes Hongkong

Editorial Board Memberships

  1. Clinical Endocrinology (2012-2016)
  2. Diabetic Medicine, Associate Editor (2003-2007)
  3. Diabetes, Obesity & Metabolism (1998-2011)
  4. Diabetes Research & Clinical Practice (since 1999)
  5. Journal of Diabetes Investigation, Associate Editor (2009-2013)
  6. Biological Signals (1990-1997)
  7. Obesity Research & Clinical Practice, Associate Editor (2006-2012)