Prof LAM Siu Ling, Karen

Prof Karen Lam

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)
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. 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; 1995-2018). This is a population-based cohort study on cardiovascular (CV) risk factors and diseases with the longest follow-up in China, which charts the rise in obesity and metabolic syndrome in Southern China, and provides the database and biobank for investigating the interaction of environmental and genetic factors underlying obesity, diabetes and CV diseases in Chinese. She has also established the Hong Kong West Diabetes Registry (HKWDR) since 2008 to investigate the factors determining the development of diabetic complications. 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; Diabetologia 2018), stroke (Neurology 2011) and other CV diseases (ATVB 2007; EHJ 2008; JAHA 2013), fatty liver diseases (Hepatology 2009), and obstructive sleep apnoea (ERJ 2009). Importantly, in the HKWDR, raised A-FABP levels predicted renal outcomes (Diabetologia 2018) and total mortality, as well as deaths due to cardiovascular diseases and infection in people with type 2 diabetes of both genders (Clin Chem 2018). Her team has elucidated the regulation of A-FABP by the C-Jun NH2-terminal kinase (JNK) inflammatory signaling (JBC 2010; Diabetes 2011; Clin Sci 2016), 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; Clin Sci 2016) highlighted the importance of JNK activation in linking adipose tissue inflammation and dysregulated adipokine secretion with diabetes and atherosclerotic diseases in obesity.

For FGF21, a hormone previously considered as a hepatokine, her paper in Diabetes 2008 provided the first evidence that FGF21 expression in 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). In view of the beneficial metabolic effects of FGF21 and its analogs in animals and humans, respectively, this paradoxical increase in FGF21 levels suggests that obesity is associated with FGF21 resistance, the mechanism of which have been elucidated by her group (Diabetes 2013) and others. Subsequent studies conducted by her group and other researchers have reported that elevated FGF21 levels are present in atherosclerosis (ATVB 2013), fatty liver and other obesity related disorders, and predict the development of diabetic nephropathy (JCEM 2015).

In genetic studies of metabolic diseases, her group has demonstrated that obesity susceptibility genes identified from GWAS in Caucasians are also relevant in Chinese (JCEM 2010; EJE 2011). They have identified the association with T2DM of an Asian specific coding variant of PAX-4 (Diabetologia 2017) and the genetic regulation of FGF21 and pigment epithelium derived factor (PEDF), also implicated in diabetic complications (Diabetes 2017 & 2018). Recently they have contributed to the discovery of novel coding sequence variants associated with lipid traits in Chinese (Nature Communications 2016) and East Asians (Nature Genetics 2017).

Selected Publications
  1. CYY Cheung, PCH Lee, C Tang, A Xu, KW Au, CHY Fong, K Ng, K Kwok, WS Chow, CY Woo, MMY Yuen, JJ Hai, KCB Tan, TH Lam, HF Tse, PC Sham, KSL Lam. Genetic regulation of pigment epithelium-derived factor (PEDF): an Exome-chip association analysis in Chinese subjects with type 2 diabetes. Diabetes [IF:7.273]2018 Oct 10 Epub ahead of print
  2. PCH Lee, CYY Cheung, YC Woo, DTW Lui, MMA Yuen, CHY Fong, WS Chow, A Xu, KSL Lam. Prospective association of circulating adipocyte fatty acid-binding protein levels with risk of renal outcomes and mortality in type 2 diabetes. Diabetologia 2018 Sep 28 Epub ahead of print [IF:6.023]
  3. YK Wong, CYY Cheung, CS Tang, KW Au, JSH Hai, PCH Lee, KK Lau, BMY Cheung, PC Sham, A Xu, KSL Lam (Co-corresponding author), HF Tse. Age-Biomarkers-Clinical (ABC) risk factor for prediction of cardiovascular events in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2018 (Accepted) [IF:6.086]
  4. PCH Lee, CYY Cheung, YC Woo, DTW Lui, MMA Yuen, CHY Fong, WS Chow, A Xu, KSL Lam. Circulating adipocyte fatty acid-binding protein concentrations predict multiple mortality outcomes among men and women with diabetes. Clin Chem 2018 Jul 18 Epub ahead of print [IF:8.636] #citations on 19/11/18: 1
  5. 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 Commun2015;6:10206 [IF:12.353] #citations on 19/11/18: 21
  6. 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;100:1368-75  [IF:5.789] #citations on 19/11/18: 32
  7. 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;33:2454-9  [IF:6.086] #citations on 19/11/18: 78
  8. 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;58:358-64  [IF:15.04] #citations on 19/11/18: 27
  9. 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 Endocrinol Metab2012;97(1):E54-8  [IF:5.789] #citations on 19/11/18: 60
  10. 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;60:486-95  [IF:7.273] #citations on 19/11/18: 69
  11. 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;34:2113-5  [IF:13.397] #citations on 19/11/18: 86
  12. 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;76:1968-75  [IF:8.055] #citations on 19/11/18: 31
  13. 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:5.789] #citations on 19/11/18: 58
  14. 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;32:132-4  [IF: 13.397]  #citations on 19/11/18: 40
  15. XM Zhang, DCY Yeung, M Karpisek, D Stejskal, F Liu, RLC Wong, *KSL Lam, *A Xu. (*co-corresponding authors). Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 2008;57:1246-53  [IF:7.273] #citations on 19/11/18: 443
  16. 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:18.881] #citations on 19/11/18: 239
  17. 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:6.086] #citations on 19/11/18: 129
  18. 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:13.397] #citations on 19/11/18: 172

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)