ORCID Profile
0000-0002-2837-5889
Current Organisations
The Royal College of Pathologists
,
Academy of Medicine
,
A*STAR
,
American College of Endocrinology
,
American College of Physicians
,
Duke-NUS Medical School
,
Lee Kong Chian School of Medicine
,
Nanyang Technological University
,
National University of Singapore
,
National University Singapore Yong Loo Lin School of Medicine
,
Royal College of Physicians of Edinburgh
,
Tan Tock Seng Hospital
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 22-05-2017
DOI: 10.1111/DME.13358
Publisher: Public Library of Science (PLoS)
Date: 30-09-2013
Publisher: The Endocrine Society
Date: 19-01-2021
Abstract: Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor. A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively. This report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.MCE.2012.07.002
Abstract: Apelin is an adipokine secreted by adipocytes. Co-expression of apelin and apelin receptor (APJ) in adipocytes implies the autocrine regulations of apelin on adipocyte functions through yet unknown molecular mechanisms. In the present study, we provide evidence that apelin, through its interaction with APJ receptor, inhibits adipogenesis of pre-adipocytes and lipolysis in mature adipocytes. The detailed molecular pathways underlying apelin signaling is proposed based on our experimental observations. Specifically, we show that apelin suppresses adipogenesis through MAPK kinase/ERK dependent pathways. And by preventing lipid droplet fragmentation, apelin inhibits basal lipolysis through AMP kinase dependent enhancement of perilipin expression and inhibits hormone-stimulated acute lipolysis through decreasing perilipin phosphorylation. Apelin induced decrease of free fatty acid release can be attributed to its dual inhibition on adipogenesis and lipolysis. This study suggests that the autocrine signaling of apelin may serve as a novel therapeutic target for obesity and other metabolic disorders.
Publisher: Springer Science and Business Media LLC
Date: 20-12-2019
DOI: 10.1038/S41467-019-13694-1
Abstract: The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. In iduals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD + levels through perturbed NAD + biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 19-11-2014
DOI: 10.1126/SCITRANSLMED.3009885
Abstract: Metformin can be repurposed as host-directed therapy for tuberculosis.
Publisher: American Diabetes Association
Date: 13-02-2014
DOI: 10.2337/DB13-1483
Abstract: We previously showed that ethnicity modifies the association between adiposity and insulin resistance. We sought to determine whether differential body fat partitioning or abnormalities in muscle insulin signaling associated with higher levels of adiposity might underlie this observation. We measured the insulin sensitivity index (ISI), percentage of body fat (%body fat), visceral (VAT) and subcutaneous (SAT) adipose tissue, liver fat, and intramyocellular lipids (IMCL) in 101 Chinese, 82 Malays, and 81 South Asians, as well as phosphorylated (p)-Akt levels in cultured myoblasts from Chinese and South Asians. Lean Chinese and Malays had higher ISI than South Asians. Although the ISI was lower in all ethnic groups when %body fat was higher, this association was stronger in Chinese and Malays, such that no ethnic differences were observed in overweight in iduals. These ethnic differences were observed even when %body fat was replaced with fat in other depots. Myoblasts obtained from lean South Asians had lower p-Akt levels than those from lean Chinese. Higher adiposity was associated with lower p-Akt levels in Chinese but not in South Asians, and no ethnic differences were observed in overweight in iduals. With higher %body fat, Chinese exhibited smaller increases in deep SAT and IMCL compared with Malays and South Asians, which did not explain the ethnic differences observed. Our study suggests that body fat partitioning does not explain interethnic differences in insulin sensitivity among Asian ethnic groups. Although higher adiposity had greater effect on skeletal muscle insulin sensitivity among Chinese, obesity-independent pathways may be more relevant in South Asians.
Publisher: The Company of Biologists
Date: 2016
DOI: 10.1242/DEV.131573
Abstract: The association between impaired fetal growth and postnatal development of obesity has been demonstrated before. By comparing adipocytes differentiated from Mesenchymal Stem Cells (MSCs) taken from the umbilical cord and derived from normal and growth restricted neonates, we identified the transcription factor SOX6 as a highly expressed gene only in growth restricted in iduals. We found that SOX6 regulates the process of adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα, and MEST. We further show that SOX6 interacts with β-catenin in adipocytes suggesting an inhibition of WNT/β-catenin signaling thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth restricted subjects harbors hypo-methylated CpGs next to SOX6 binding motifs and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Singapore
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Melvin Khee Shing Leow.