Dr Chai Ng

Dr Chai Ng

Conjoint Lecturer

PhD 

Medicine & Health
School of Clinical Medicine

My research program uses high-throughput automated patch-clamp electrophysiology to assess the function of genetic variants found in ion channels expressed in the heart and brain. The focus of my current research is to provide functional evidence for variant reclassification in long QT syndromes and epilepsy.

Through my research, I aim to establish the threshold for determining normal and abnormal function for a range of potassium and sodium channels that are important for regulating the rhythms of the heart and brain.

I have successfully validated our functional genomics KCNH2 assay against a set of known benign and pathogenic KCNH2 variants, which allows us to produce functional evidence that can be used for variant reclassification in the clinic. I will transfer my knowledge and skills to other ion channelopathies and establish the Victor Chang Cardiac Research Institute as a functional genomics testing centre for long QT Syndromes and ion channelopathies.

Phone
+61 2 9295 8687
Location
The Victor Chang Cardiac Research Institute, 405 Liverpool St, Darlinghurst NSW 2010
  • Book Chapters | 2014
    Vandenberg JI; Ng CA; Mann SA; Perry MD, 2014, 'Voltage-Gated Potassium Channels (Kv10-Kv12)', in Reference Module in Biomedical Research, http://dx.doi.org/10.1016/B978-0-12-801238-3.04809-1
  • Journal articles | 2023
    Copier JS; Bootsma M; Ng CA; Wilde AAM; Bertels RA; Bikker H; Christiaans I; van der Crabben SN; Hol JA; Koopmann TT; Knijnenburg J; Lommerse AAJ; van der Smagt JJ; Bezzina CR; Vandenberg JI; Verkerk AO; Barge-Schaapveld DQCM; Lodder EM, 2023, 'Reclassification of a likely pathogenic Dutch founder variant in KCNH2; implications of reduced penetrance', Human molecular genetics, 32, pp. 1072 - 1082, http://dx.doi.org/10.1093/hmg/ddac261
    Journal articles | 2022
    Jiang C; Richardson E; Farr J; Hill AP; Ullah R; Kroncke BM; Harrison SM; Thomson KL; Ingles J; Vandenberg JI; Ng CA, 2022, 'A calibrated functional patch-clamp assay to enhance clinical variant interpretation in KCNH2-related long QT syndrome', American Journal of Human Genetics, 109, pp. 1199 - 1207, http://dx.doi.org/10.1016/j.ajhg.2022.05.002
    Journal articles | 2022
    Ng CA; Ullah R; Farr J; Hill AP; Kozek KA; Vanags LR; Mitchell DW; Kroncke BM; Vandenberg JI, 2022, 'A massively parallel assay accurately discriminates between functionally normal and abnormal variants in a hotspot domain of KCNH2', American Journal of Human Genetics, 109, pp. 1208 - 1216, http://dx.doi.org/10.1016/j.ajhg.2022.05.003
    Journal articles | 2022
    Ng CA; Vandenberg JI, 2022, 'When it takes two to get one into trouble', Heart Rhythm, 19, pp. 293 - 294, http://dx.doi.org/10.1016/j.hrthm.2021.10.017
    Journal articles | 2021
    Li JV; Ng CA; Cheng D; Zhou Z; Yao M; Guo Y; Yu ZY; Ramaswamy Y; Ju LA; Kuchel PW; Feneley MP; Fatkin D; Cox CD, 2021, 'Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations', Communications Biology, 4, pp. 1038, http://dx.doi.org/10.1038/s42003-021-02528-w
    Journal articles | 2021
    Ng CA; Farr J; Young P; Windley MJ; Perry MD; Hill AP; Vandenberg JI, 2021, 'Heterozygous KCNH2 variant phenotyping using Flp-In HEK293 and high-Throughput automated patch clamp electrophysiology', Biology Methods and Protocols, 6, pp. 1 - 9, http://dx.doi.org/10.1093/biomethods/bpab003
    Journal articles | 2020
    Kozek KA; Glazer AM; Ng CA; Blackwell D; Egly CL; Vanags LR; Blair M; Mitchell D; Matreyek KA; Fowler DM; Knollmann BC; Vandenberg JI; Roden DM; Kroncke BM, 2020, 'High-throughput discovery of trafficking-deficient variants in the cardiac potassium channel KV11.1', Heart Rhythm, 17, pp. 2180 - 2189, http://dx.doi.org/10.1016/j.hrthm.2020.05.041
    Journal articles | 2020
    Ng CA; Perry MD; Liang W; Smith NJ; Foo B; Shrier A; Lukacs GL; Hill AP; Vandenberg JI, 2020, 'High-throughput phenotyping of heteromeric human ether-à-go-go-related gene potassium channel variants can discriminate pathogenic from rare benign variants', Heart Rhythm, 17, pp. 492 - 500, http://dx.doi.org/10.1016/j.hrthm.2019.09.020
    Journal articles | 2020
    Perry MD; Ng CA; Mangala MM; Ng TYM; Hines AD; Liang W; Xu MJO; Hill AP; Vandenberg JI, 2020, 'Pharmacological activation of IKrin models of long QT Type 2 risks overcorrection of repolarization', Cardiovascular Research, 116, pp. 1434 - 1445, http://dx.doi.org/10.1093/cvr/cvz247
    Journal articles | 2017
    Phan K; Ng CA; David E; Shishmarev D; Kuchel PW; Vandenberg JI; Perry MD, 2017, 'The S1 helix critically regulates the finely tuned gating of Kv11.1 channels', Journal of Biological Chemistry, 292, pp. 7688 - 7705, http://dx.doi.org/10.1074/jbc.M117.779298
    Journal articles | 2016
    Cox CD; Bae C; Ziegler L; Hartley S; Nikolova-Krstevski V; Rohde PR; Ng CA; Sachs F; Gottlieb PA; Martinac B, 2016, 'Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension', Nature Communications, 7, http://dx.doi.org/10.1038/ncomms10366
    Journal articles | 2016
    Ng CA; Gravel AE; Perry MD; Arnold AA; Marcotte I; Vandenberg JI, 2016, 'Tyrosine residues from the s4-s5 linker of kv11.1 channels are critical for slow deactivation', Journal of Biological Chemistry, 291, pp. 17293 - 17302, http://dx.doi.org/10.1074/jbc.M116.729392
    Journal articles | 2016
    Perry MD; Ng CA; Phan K; David E; Steer K; Hunter MJ; Mann SA; Imtiaz M; Hill AP; Ke Y; Vandenberg JI, 2016, 'Rescue of protein expression defects may not be enough to abolish the pro-arrhythmic phenotype of long QT type 2 mutations', Journal of Physiology, 594, pp. 4031 - 4049, http://dx.doi.org/10.1113/JP271805
    Journal articles | 2015
    Perry MD; Ng CA; Mann SA; Sadrieh A; Imtiaz M; Hill AP; Vandenberg JI, 2015, 'Getting to the heart of hERG K+ channel gating', Journal of Physiology, 593, pp. 2575 - 2585, http://dx.doi.org/10.1113/JP270095
    Journal articles | 2014
    Ke Y; Hunter MJ; Ng CA; Perry MD; Vandenberg JI, 2014, 'Role of the cytoplasmic N-terminal cap and Per-Arnt-Sim (PAS) domain in trafficking and stabilization of Kv11.1 channels', Journal of Biological Chemistry, 289, pp. 13782 - 13791, http://dx.doi.org/10.1074/jbc.M113.531277
    Journal articles | 2014
    Ng CA; Phan K; Hill AP; Vandenberg JI; Perry MD, 2014, 'Multiple interactions between cytoplasmic domains regulate slow deactivation of Kv11.1 channels', Journal of Biological Chemistry, 289, pp. 25822 - 25832, http://dx.doi.org/10.1074/jbc.M114.558379
    Journal articles | 2014
    Sadrieh A; Domanski L; Pitt-Francis J; Mann SA; Hodkinson EC; Ng CA; Perry MD; Taylor JA; Gavaghan D; Subbiah RN; Vandenberg JI; Hill AP, 2014, 'Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2', Nature Communications, 5, http://dx.doi.org/10.1038/ncomms6069
    Journal articles | 2013
    Ke Y; Ng CA; Hunter MJ; Mann SA; Heide J; Hill AP; Vandenberg JI, 2013, 'Trafficking defects in PAS domain mutant Kv11.1 channels: Roles of reduced domain stability and altered domain-domain interactions', Biochemical Journal, 454, pp. 69 - 77, http://dx.doi.org/10.1042/BJ20130328
    Journal articles | 2013
    Ng CA; Ke Y; Perry MD; Tan PS; Hill AP; Vandenberg JI, 2013, 'C-Terminal β9-Strand of the Cyclic Nucleotide-Binding Homology Domain Stabilizes Activated States of Kv11.1 Channels', PLoS ONE, 8, http://dx.doi.org/10.1371/journal.pone.0077032
    Journal articles | 2013
    Perry MD; Ng CA; Vandenberg JI, 2013, 'Pore helices play a dynamic role as integrators of domain motion during Kv11.1 channel inactivation gating', The Journal of Biological Chemistry, 288, pp. 11482 - 11491, http://dx.doi.org/10.1074/jbc.M113.461442
    Journal articles | 2013
    Perry MD; Wong S; Ng CA; Vandenberg JI, 2013, 'Hydrophobic interactions between the voltage sensor and pore mediate inactivation in Kv11.1 channels', Journal of General Physiology, 142, pp. 275 - 288, http://dx.doi.org/10.1085/jgp.201310975
    Journal articles | 2012
    Ng CA; Perry M; Tan P; Hill A; Kuchel PW; Vandenberg JI, 2012, 'The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating', PLoS ONE, 7, pp. e31640, http://dx.doi.org/10.1371/journal.pone.0031640
    Journal articles | 2012
    Tan PS; Perry MD; Ng C; Vandenberg JI; Hill A, 2012, 'Voltage-sensing domain mode shift is coupled to the activation gate by the N-terminal tail of hERG channels', Journal of General Physiology, 140, pp. 293 - 306, http://dx.doi.org/10.1085/jgp.201110761
    Journal articles | 2012
    Vandenberg JI; Ng CA, 2012, 'Insights into hERG K+ channel structure and function from NMR studies', European Biophysics Journal With Biophysics Letters, 42, pp. 71 - 79, http://dx.doi.org/10.1007/s00249-012-0808-6
    Journal articles | 2011
    Ng C; Hunter M; Perry M; Mobli M; Ke Y; Kuchel PW; King GF; Stock D; Vandenberg JI; Hunter M, 2011, 'The N-terminal tail of hERG contains an amphipathic alpha-helix that regulates channel deactivation', PLoS One, 6, pp. e16191, http://dx.doi.org/10.1371/journal.pone.0016191
    Journal articles | 2009
    Ng CA; Oehme DP; Kato Y; Tanokura M; Brownlee RTC, 2009, 'Binding of an RNA pol II ligand to the ww domain of Pin1 using molecular dynamics docking simulations', Journal of Chemical Theory and Computation, 5, pp. 2886 - 2897, http://dx.doi.org/10.1021/ct900190n
    Journal articles | 2008
    Ng CA; Kato Y; Tanokura M; Brownlee RTC, 2008, 'Structural characterisation of PinA WW domain and a comparison with other Group IV WW domains, Pin1 and Ess1', Biochimica et Biophysica Acta - Proteins and Proteomics, 1784, pp. 1208 - 1214, http://dx.doi.org/10.1016/j.bbapap.2008.04.026
    Journal articles | 2007
    Kato Y; Ng CA; Brownlee RTC; Tanokura M, 2007, 'PinA from Aspergillus nidulans binds to pS/pT-P motifs using the same Loop I and XP groove as mammalian Pin1', Biochimica et Biophysica Acta - Proteins and Proteomics, 1774, pp. 1208 - 1212, http://dx.doi.org/10.1016/j.bbapap.2007.06.006
    Journal articles | 2007
    Ng CA; Zhao W; Dang J; Bergdahl M; Separovic F; Brownlee RTC; Metzger RP, 2007, 'The conformation of acetylated virginiamycin M1 and virginiamycin M1 in explicit solvents', Biochimica et Biophysica Acta - Proteins and Proteomics, 1774, pp. 610 - 618, http://dx.doi.org/10.1016/j.bbapap.2007.03.002
    Journal articles | 2005
    Dang J; Metzger RP; Brownlee RTC; Ng CA; Bergdahl M; Separovic F, 2005, 'The conformational flexibility of the antibiotic virginiamycin M 1', European Biophysics Journal, 34, pp. 383 - 388, http://dx.doi.org/10.1007/s00249-005-0464-1
  • Preprints | 2022
    Copier JS; Bootsma M; Ng C; Wilde AAM; Bertels RA; Bikker H; Christiaans I; van der Crabben SN; Hol JA; Koopmann TT; Knijnenburg J; Lommerse AAJ; van der Smagt JJ; Bezzina CR; Vandenberg JI; Verkerk AO; Barge-Schaapveld DQCM; Lodder EM, 2022, Reclassification of a likely pathogenic Dutch founder variant in KCNH2; implications of reduced penetrance, , http://dx.doi.org/10.1101/2022.08.05.502917
    Conference Abstracts | 2022
    Ullah R; Ng CA; Vanags L; Mitchell D; Vandenberg J; Kroncke B, 2022, 'Abstract 12815: High Throughput Variant Identification in the S3-S5 Helices of KCNH2 (hERG)', in Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, pp. a12815 - a12815, http://dx.doi.org/10.1161/circ.146.suppl_1.12815
    Conference Abstracts | 2021
    Jiang C; Farr J; Hill A; Kroncke B; Ingles J; Vandenberg J; Ng CA, 2021, 'Abstract 11857: Benchmarking a Functional Assay to Assist Clinical Classification of Variants of Uncertain Significance in KCNH2 (Long QT Syndrome Type 2)', in Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, http://dx.doi.org/10.1161/circ.144.suppl_1.11857
    Preprints | 2021
    Jiang C; Richardson E; Farr J; Hill A; Ullah R; Kroncke B; Harrison S; Thomson K; Ingles J; Vandenberg J; Ng C-A, 2021, A calibrated functional patch clamp assay to enhance clinical variant interpretation in KCNH2-related long QT syndrome, , http://dx.doi.org/10.1101/2021.12.13.472492
    Conference Abstracts | 2021
    Li J; Ann Ng C; Cheng D; Cox CD, 2021, 'Modified N-Linked Glycosylation Status Predicts Trafficking Defective Piezo1 Channel Mutations', in Biophysical Journal, Elsevier BV, Vol. 120, pp. 236a - 237a, http://dx.doi.org/10.1016/j.bpj.2020.11.1562
    Conference Papers | 2021
    Li J; Ng CA; Cheng D; Cox CD, 2021, 'Modified N-Linked Glycosylation Status Predicts Trafficking Defective', in BIOPHYSICAL JOURNAL, CELL PRESS, ELECTR NETWORK, pp. 236A - 237A, presented at 65th Annual Meeting of the Biophysical-Society (BPS), ELECTR NETWORK, 22 February 2021 - 26 February 2021, https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000629601401400&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
    Conference Abstracts | 2021
    Ullah R; Ng C; Farr J; Hill A; kozek K; Vanags L; Mitchell D; Vandenberg J; Kroncke B, 2021, 'Abstract 11153: Massively Parallel, High-Throughput Approach for Identifying Defective KCNH2 (hERG) Variants', in Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, http://dx.doi.org/10.1161/circ.144.suppl_1.11153
    Preprints | 2021
    Vandenberg J; Lau C; Flood E; Hunter M; Ng C-A; Bouwer J; Stewart A; Perozo E; Allen T, 2021, Structural Basis for Rapid Voltage Dependent Inactivation of HERG Potassium Channels, , http://dx.doi.org/10.21203/rs.3.rs-1105661/v1
    Conference Presentations | 2021
    Ng C-A; Ullah R; Farr J; Hill A; Kozek K; Vanags L; Mitchell D; Kroncke B; Vandenberg J, 2021, 'A Massively Parallel Trafficking Assay Accurately Predicts Loss of Channel Function in KCNH2 Variants', http://dx.doi.org/10.1101/2021.07.10.451881
    Preprints | 2020
    Kozek KA; Glazer AM; Ng C-A; Blackwell D; Egly CL; Vanags LR; Blair M; Mitchell D; Matreyek KA; Fowler DM; Knollmann BC; Vandenberg J; Roden DM; Kroncke BM, 2020, High-throughput discovery of trafficking-deficient variants in the cardiac potassium channelKCNH2: Deep mutational scan ofKCNH2trafficking, , http://dx.doi.org/10.1101/2020.02.17.952606
    Preprints | 2020
    Li JV; Ng C-A; Cheng D; Yao M; Guo Y; Yu Z-Y; Ramaswamy Y; Ju LA; Kuchel PW; Feneley MP; Fatkin D; Cox CD, 2020, Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations, , http://dx.doi.org/10.1101/2020.11.30.404962
    Datasets | 2016
    Vandenberg J; Ng CA, 2016, Faculty Opinions recommendation of Tetrameric Assembly of K+ Channels Requires ER-Located Chaperone Proteins., , http://dx.doi.org/10.3410/f.727072588.793526218
    Conference Abstracts | 2014
    Cox CD; Ng CA; Bavi N; Martinac B, 2014, 'Mechanically-Induced Gating in PKD2L1 (Trpp2): Calcium-Induced Activation Masquerading as Force Sensitivity?', in BIOPHYSICAL JOURNAL, CELL PRESS, CA, San Francisco, Vol. 112, pp. 311A - 311A, presented at 58th Annual Meeting of the Biophysical-Society, CA, San Francisco, 15 February 2014 - 19 February 2014, http://dx.doi.org/10.1016/j.bpj.2016.11.1686
    Conference Abstracts | 2012
    Ke Y; Hunter M; Ng CA; Vandenberg J, 2012, 'Domain Misfolding and Destabilisation of Domain–Domain Interactions Both Contribute to Defective Trafficking of hERG EAG Domain Mutant Channels', in Heart, Lung and Circulation, Vol. 21, pp. 860 - 861, http://dx.doi.org/10.1016/j.hlc.2012.08.025
    Other | 2012
    Ng CA; Kuchel PW; Vandenberg JI, 2012, Solution nmr structure of the S4S5 linker of herg potassium channel, Worldwide Protein Data Bank, , http://dx.doi.org/10.2210/pdb2le7/pdb
    Conference Abstracts | 2012
    Tan PS; Perry M; Chai AN; Vandenberg JI; Hill AP, 2012, 'Bimodal Regulation of hERG Gating by the N-Terminal Tail Revealed by Voltage Clamp Fluorometry', in BIOPHYSICAL JOURNAL, CELL PRESS, CA, San Diego, Vol. 102, pp. 328A - 328A, presented at 56th Annual Meeting of the Biophysical-Society, CA, San Diego, 25 February 2012 - 29 February 2012, http://dx.doi.org/10.1016/j.bpj.2011.11.1800
    Other | 2011
    Ng CA; Hunter MJ; Mobli M; King GF; Kuchel PW; Vandenberg JI, 2011, Solution NMR structure of the N-terminal PAS domain of HERG potassium channel, Worldwide Protein Data Bank, , http://dx.doi.org/10.2210/pdb2l0w/pdb
    Other | 2007
    Ng CA; Kato Y; Tanokura M; Brownlee RTC, 2007, Structure Characterisation of PINA WW Domain and Comparison with other Group IV WW Domains, PIN1 and ESS1, Worldwide Protein Data Bank, , http://dx.doi.org/10.2210/pdb2jv4/pdb
    Conference Abstracts |
    Phan K; Ng C; McNitt S; Moss A; Zareba W; Perry M; Vandenberg J, 'The role of in vitro phenotypes for clinical risk stratification of sudden death in Long QT Syndrome Type 2', in Heart, Lung and Circulation, Elsevier, Vol. 24, pp. S232 - S233, presented at Heart, Lung and Circulation, http://dx.doi.org/10.1016/j.hlc.2015.06.289

My current research focuses on developing high-throughput functional genomics assays to determine biological threshold that a variant can be classified as functionally abnormal and improve risk stratification for sudden cardiac arrest in individual that have long QT syndrome.

2021 MRFF Genomics Health Futures Mission grant - High throughput functional genomics assays for ion channelopathies ($2.9m)

Young Biophysicist of the year 2013 - Australian Society for Biophysics