Associate Professor, Pengiran Anak Puteri Rashidah Sa'adatul Bolkiah Institute of Health Sciences
Dr Chen was a practising pathologist and a teaching academic in China before she decided to pursue her scientific interest full-time in the molecular functional studies of ion channels in neuromuscular diseases. She first did an MD/PhD double degrees at the University of Bern, Switzerland and then worked as a postdoc at the National Neuroscience Institute in Singapore and later University of Edinburgh, UK. She was a Senior Research Fellow at Edinburgh before joining UBD recently as an Associate Professor in Pathology. Dr Chen has spent the last decade or so working on the physiological properties and molecular regulation on the trafficking of big current potassium (BK) channel. She was also the holder of a number of grants throughout her career. Coming one full circle, at UBD now, in addition to teaching medicine and biomedical science students at UBD, Dr Chen has now started looking into the clinical potentials of using BK channel as a treatment target for neuromuscular diseases, diabete mellitus and breast cancer.
MD/PhD in Neuroscience (University of Bern, Switzerland)
Ion channel diseases
Obesity and diabete mellitus
In Brunei Darussalam, breast cancer has remained consistently as the leading cause of death and a worrying trend of younger age of onset has emerged in recent years. High mortality in poor prognostic breast cancer, such as the triple negative, patients has been attributed to the lack of suitable biomarkers for therapeutic targeting. The functionally diverse and ubiquitously expressed calcium- and voltage-activated potassium BK channel has recently been shown to promote cancer cell proliferation, invasion and migration during the carcinogenic process. Preliminary evidence in aggressive glioma and cancer cell lines has demonstrated the promising potential of the channel, especially the gBK glioma splicing variant, serving as both a malignancy marker and an immuno-target. We, therefore, aim to establish for the first time the role of the high-grade-tumour-specific BK complex in the carcinogenesis of breast cancer. The expression spectrum of the complex (channel’s pore forming splicing variants and associated accessory subunits) in general cancer progression and breast tumours of different clinical stages and their cell proliferative and migratory effects will be studied. Establishment of this high-grade-tumour-specific BK complex as a prognosis marker will form the basis of preliminary pharmacological targeting of BK channel specific to breast cancer carcinogenesis.
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1. Duncan PJ, Bi D, McClafferty H, Chen L, Tian L, Shipston MJ. (2019) S-Acylation controls functional coupling of BK channel pore-forming α-subunits and β1-subunits. J Biol Chem. [Epub ahead of print].
2. ZH Lu, N Azman, MIR Petalcorin, N Shafqat, L Chen (2018). Population Analysis of Pharmacogenetic Polymorphisms. In Encyclopedia of Bioinformatics and Computational Biology. Vol 3, p379, Elsevier
3. Chen L, Bi D, Lu ZH, McClafferty H, Shipston MJ. (2017) Distinct domains of the β1-subunit cytosolic N-terminus control surface expression and functional properties of large conductance calcium-activated potassium (BK) channels. J Biol Chem. 292(21):8694-8704.
4. Chen L, Duncan P, Macgregor D, Liang Zh and Shipston MJ. (2015) Illuminating the (Electro)physiology of Anterior Pituitary Corticotrophs, in Neuroendocrinology of Stress (eds J. Russell and M. Shipston), John Wiley & Sons, Ltd, Chichester, UK.
5. Chen L, Bi D, Tian L, McClafferty H, Steeb F, Ruth P, Knaus HG, Shipston MJ. (2013) Palmitoylation of the β4-subunit regulates surface expression of large conductance calcium-activated potassium channel splice variants. J Biol Chem. 288(18):13136-44.
1. Chen L, Bi D, Lu ZH, McClafferty H, Shipston MJ. (2017) Distinct domains of the β1-subunit cytosolic N-terminus control surface expression and functional properties of large conductance calcium-activated potassium (BK) channels. J Biol Chem.
2. Chen L, Bi D, Tian L, McClafferty H, Steeb F, Ruth P, Knaus HG, Shipston MJ. (2013) Palmitoylation of the β4-subunit regulates surface expression of large conductance calcium-activated potassium channel splice variants. J Biol Chem. 288(18):13136-44.
3. Chen L, Jeffries O, Rowe IC, Liang Z, Knaus HG, Ruth P, Shipston MJ. (2010) Membrane trafficking of large conductance calcium-activated potassium channels is regulated by alternative splicing of a transplantable, acidic trafficking motif in the RCK1-RCK2 linker. J Biol Chem. 285(30):23265-75.
4. Tian L, Jeffries O, McClafferty H, Molyvdas A, Rowe IC, Saleem F, Chen L, Greaves J, Chamberlain LH, Knaus HG, Ruth P, Shipston MJ. (2008) Palmitoylation gates phosphorylation-dependent regulation of BK potassium channels. Proc Natl Acad Sci U S A.105(52):21006-11.
5. Tian L, Chen L, McClafferty H, Sailer CA, Ruth P, Knaus HG, Shipston MJ. (2006) A noncanonical SH3 domain binding motif links BK channels to the actin cytoskeleton via the SH3 adapter cortactin. FASEB J. 20(14):2588-90.
6. Chen L, Tian L, MacDonald SH, McClafferty H, Hammond MS, Huibant JM, Ruth P, Knaus HG, Shipston MJ. (2005) Functionally diverse complement of large conductance calcium- and voltage-activated potassium channel (BK) alpha-subunits generated from a single site of splicing. J Biol Chem. 280(39):33599-609.
7. Chen L1, Schaerer M, Lu ZH, Lang D, Joncourt F, Weis J, Fritschi J, Kappeler L, Gallati S, Sigel E, Burgunder JM. (2004) Exon 17 skipping in CLCN1 leads to recessive myotonia congenita. Muscle Nerve. 29(5):670-6.
L. Chen (PI) et. al. Investigation of BK channel as a potential prognostic biomarker and therapeutic target for breast cancer. FIC Grant. BND50,500, 2018-2020