Dr Donna Lai

Senior Lecturer
Bosch Institute, School of Medical Sciences

Telephone 9351 8787/9351 4576
Fax 9351 8400/9114 0520

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Research interests

I am interested in developing innovative molecular biology techniques to tackle complex real-world problems in biomedical research, in particular, the roles of Neuregulin 1 (NRG1) in the regulation of cardiomyocyte proliferation and differentiation and its molecular mechanisms.

Heart disease is one of the Australia’s largest health problems. Coronary heart disease accounted for 14% of all deaths in Australia in 2012. About 30,000 Australians are diagnosed with heart failure every year and nearly 23 million people have heart failure worldwide. Progressive loss of cardiomyocytes due to apoptosis or programmed cell death may be responsible for progression of heart failure.

The NRG1 family of ligands activates ErbB receptor tyrosine kinases and mediates cell proliferation, differentiation and survival in many tissues. NRG1/ErbB signaling is not only crucial for the development and growth of fetal heart but also important in maintenance of the structural and functional integrity of the adult heart. We have been investigating the roles of NRG1 in the regulation of cardiomyocyte proliferation and differentiation since 1997. We have demonstrated that treatment with NRG1 promotes proliferation, myofilament organization, and differentiation of cultured cardiomyocytes.

Teaching and supervision

Applications of molecular biology techniques in medical research

Current projects

Investigation of cardiomyocyte proliferation and cell metabolism through Neuregulin1/ErbB signalling

Description:There is increasing evidence available showing the variety of biochemical and biological effect NRG1 has on cardiomyocyte cells. A low or impaired NRG1/ErbB signaling is found in chronic heart failures and its levels in blood circulation are associated with heart failure severity. Treatments of cancer using anti-ErbB antibodies and/or chemotherapy (e.g. doxorubicin etc) often produce undesirable cardiovascular side effects, such as heart failure. On the other hand, NRG1 secretion by cardiovascular endothelial cells has been shown to protect ischemic and prostrated myocardial cells and improve cardiac function. We have demonstrated that treatment with NRG1 promotes proliferation, myofilament organization, and differentiation of cultured cardiomyocytes.Furthermore, NRG1 can inhibit the apoptosis of myocardial cells.

This project will examine the effect of NRG1 on cardiomyocyte proliferation, differentiation and cell metabolism under normal or cell-stressed conditions. Candidates will work in a state-of-the-art Bosch Molecular Biology Facility laboratories with all capabilities of tissue culture, live cell analysis, nucleic acid and protein analyses.

Selected grants

2014

  • CLARIOstar Multifunctional Microplate Reader for Shared Used at the Open Access, Multi-User Molecular Biology Core Facility; Huang M, Scolyer R, Fraser S, Sahni S, Speranza T, Owens T, Barrs V, Ju Y, Kovacevic Z, Lu Z, Camp A, Slobedman B, Morris B, Oliver B, Dos Remedios C, Kalinowski D, Fu D, Lai D, Lovicu F, Allbutt H, Triccas J, Burgess J, Kril J, Dixon K, Rendina L, Byrne M, King N, Groundwater P, Williamson P, Ho J, Dong Q, Bao B, Assinder S, McLennan S, Richardson D, Ammit A, Sharland A, Hardikar A, Hong A, Hambly B, Lee C, Murphy C, Goldsbury C, Johnstone D, Lane D, Hibbs D, Joshua D, Huq F, Halliday G, Sutherland G, Zreiqat H, Lok H, Lyons G, Jansson P, Black J, Zhu L, Sunde M, Day M, Naylor M, Buckland M, Murray M, Shafie N, Lay P, Poronnik P, Codd R, Mason R, Ryan R, Christopherson R, de Graaf S; National Health and Medical Research Council (NHMRC)/Equipment Grants.

2013

  • QX100 Droplet Digital PCR system for Shared Used at the Open Access, Multi-User Molecular Biology Core Facility; Richardson D, Kril J, Murphy C, Vandenberg R, Rendina L, Dos Remedios C, Ju Y, Kovacevic Z, Lyons G, Sutherland G, Lay P, Ammit A, Lai D, Morris B, Day M, Dong Q, Bao B, Huang M, Camp A, Boyer M, Whittington R, Byrne M, Hanrahan J, Fu D, Jansson P, Lane D, Bagley E, Hibbs D, Zhang D, Fraser S, Scolyer R, Black J, Halliday G, Christie M, Zreiqat H, Murray M, Slobedman B, Naylor M, Burgess J, Triccas J, Mason R, Chadban S, Combes V, Lovicu F, McLennan S, Kalinowski D, Sharland A, Johnstone D, Groundwater P, Dixon K, Zhou F, Lovejoy D, Lu Z, Zhu L, Goldsbury C, Witting P, Buckland M, Assinder S, Purdie (Williams) A, Codd R, Owens T, Hambly B; National Health and Medical Research Council (NHMRC)/Equipment Grants.
  • Robotic High Throughput Western Analysis for the Open Access, Multi-User Sydney Cancer Research Core Facility; Richardson D, Scolyer R, Boyer M, Halliday G, Damian D, Christopherson R, Joshua D, Kench J, Hong A, Murray M, Lee C, Kalinowski D, Naylor M, Lay P, Lyons G, Kovacevic Z, Mason R, Dixon K, Chan-Ling T, Hawkins C, Sunde M, Lovejoy D, Owens T, Rendina L, Jansson P, Dos Remedios C, Charles (nee Slaviero) K, Lane D, Witting P, Dong Q, Ammit A, Groundwater P, Assinder S, Bao B, Byrne S, Zhou F, Buckland M, Grewal T, Huq F, Lai D, Codd R, Zhang D, Fu D, de Graaf S, Huang M, Payne R, Slobedman B, Barrs V, Ho J, Williamson P, Murphy C; DVC Research/Equipment Grant.

2012

  • GeneAtlas Personal Microarray System; Richardson D, Scolyer R, Stocker R, Weninger W, Black J, Allen D, Murray M, Mason R, Twigg S, King N, Horvath L, Lovicu F, Lee C, Halliday G, Lovejoy D, Joshua D, Sharland A, Roufogalis B, Hambly B, Morris B, Bao B, Bishop A, Hibbs D, Lane D, Zhou F, Hanrahan J, Dixon K, Rendina L, Byrne M, Naylor M, Cole N, Jansson P, Dong Q, Codd R, Payne R, Assinder S, Chadban S, Fraser S, McLennan S, Suryo Rahmanto A, Lai D, Yu Y, Ju Y, Buckland M, Kovacevic Z, Saletta F, Zreiqat H, Kalinowski D, Groundwater P, Simes R, Zhang D, Boyer M, Murphy C; National Health and Medical Research Council (NHMRC)/Equipment Grants.

Selected publications

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Journals

  • Sabri, A., Lai, D., D'Silva, A., Seeho, S., Kaur, J., Ng, C., Hyett, J. (2014). Differential Placental Gene Expression in Term Pregnancies Affected by Fetal Growth Restriction and Macrosomia. Fetal Diagnosis and Therapy: clinical advances and basic research, 36(2), 173-180. [More Information]
  • Lui, W., Zhang, X., Song, C., Bao, B., Lai, D., Mou, J., Jiang, T., Wang, N. (2014). Expression and characterization of a soluble VEGF receptor 2 protein. Cell & Bioscience, 4(1), 1-10. [More Information]
  • Mills, J., Sheahan, P., Lai, D., Kril, J., Janitz, M., Sutherland, G. (2014). The alternative splicing of the apolipoprotein E gene is unperturbed in the brains of Alzheimer's disease patients. Molecular Biology Reports, 41(10), 6365-6376. [More Information]
  • Zhang, X., Lai, D., Bao, B., Hambly, B., Gillies, M. (2013). Triamcinolone Acetonide Inhibits p38MAPK Activation and Neuronal Apoptosis in Early Diabetic Retinopathy. Current Molecular Medicine, 13(6), 946-958. [More Information]
  • Desbonnet, L., O'Tuathaigh, C., Clarke, G., O'Leary, C., Petit, E., Clarke, N., Tighe, O., Lai, D., Harvey, R., Cryan, J., et al (2012). Phenotypic effects of repeated psychosocial stress during adolescence in mice mutant for the schizophrenia risk gene neuregulin-1: a putative model of gene x environment interaction. Brain, Behavior, and Immunity, 26(4), 660-671. [More Information]
  • Ju, Y., Liu, J., Lee, B., Lai, D., Woodcock, E., Lei, M., Cannell, M., Allen, D. (2011). Distribution and Functional Role of Inositol 1,4,5-trisphosphate Receptors in Mouse Sinoatrial Node. Circulation Research, 109(8), 848-857. [More Information]
  • He, Z., Lai, D., Wakelin, L. (2010). [Co(III)(cyclen)Cl(2)]Cl is selectively cytotoxic to human leukaemia cells. European Journal of Pharmacology, 637(1-3), 11-15. [More Information]
  • Duffy, L., Cappas, E., Lai, D., Boucher, A., Karl, T. (2010). Cognition in Transmembrane Domain Neuregulin 1 Mutant Mice. Neuroscience, 170(3), 800-807. [More Information]
  • Walsh, J., Tighe, O., Lai, D., Harvey, R., Karayiorgou, M., Gogos, J., Waddington, J., O'Tuathaigh, C. (2010). Disruption of thermal nociceptive behaviour in mice mutant for the schizophrenia-associated genes NRG1, COMT and DISC1. Brain Research, 1348 (C), 114-119. [More Information]
  • Lai, D., Liu, X., Forrai, A., Wolstein, O., Michalicek, J., Ahmed, I., Garratt, A., Birchmeier, C., Zhou, M., Hartley, L., et al (2010). Neuregulin 1 Sustains the Gene Regulatory Network in Both Trabecular and Nontrabecular Myocardium. Circulation Research, 107(6), 715-727. [More Information]
  • O'Tuathaigh, C., Harte, M., O'Leary, C., O'Sullivan, G., Blau, C., Lai, D., Harvey, R., Tighe, O., Fagan, A., Kerskens, C., et al (2010). Schizophrenia-related endophenotypes in heterozygous neuregulin-1 'knockout' mice. European Journal of Neuroscience, 31(2), 349-358. [More Information]
  • Tomiyama, K., O'Tuathaigh, C., O'Sullivan, G., Kinsella, A., Lai, D., Harvey, R., Tighe, O., Croke, D., Koshikawa, N., Waddington, J. (2009). Phenotype of spontaneous orofacial dyskinesia in neuregulin-1 ‘knockout’ mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33, 330-333. [More Information]
  • O'Tuathaigh, C., O'Connor, A., O'Sullivan, G., Lai, D., Harvey, R., Croke, D., Waddington, J. (2008). Disruption to social dyadic interactions but not emotional/anxiety-related behaviour in mice with heterozygous ‘knockout’ of the schizophrenia risk gene neuregulin-1. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32(2), 462-466. [More Information]
  • Zhang, X., Bao, B., Lai, D., Rapkins, R., Gillies, M. (2008). Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier through Differential Regulation of VEGF-A and its Receptors in Early Diabetic Rat Retinas. Diabetes, 57(4), 1026-1033. [More Information]
  • Ju, Y., Chu, Y., Chaulet, H., Lai, D., Gervasio, O., Graham, R., Cannell, M., Allen, D. (2007). Store-operated Ca2+ influx and expression of TRPC genes in mouse sinoatrial node. Circulation Research, 100(11), 1605-1614. [More Information]
  • Liu, X., Gu, X., Li, Z., Li, X., Li, H., Chang, J., Chen, P., Jin, J., Xi, B., Chen, D., Lai, D., et al (2006). Neuregulin-1/erbB-Activation Improves Cardiac Function and Survival in Models of Ischemic, Dilated, and Viral Cardiomyopathy. Journal of the American College of Cardiology, 48(7), 1438-1447. [More Information]
  • Kirk, E., Hyun, C., Thomson, P., Lai, D., Castro, M., Biben, C., Buckley, M., Martin, I., Moran, C., Harvey, R. (2006). Quantitative Trait Loci Modifying Cardiac Atrial Septal Morphology and Risk of Patent Foramen Ovale in the Mouse. Circulation Research, 98(5), 651-658. [More Information]
  • Stennard, F., Costa, M., Lai, D., Biben, C., Furtado, M., Solloway, M., McCulley, D., Leimena, C., Preis, J., Dunwoodie, S., et al (2005). Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation. Development (Cambridge), 132(10), 2451-2462. [More Information]
  • Linhares, V., Almeida, N., Menezes, D., Elliott, D., Lai, D., Beyer, E., Campos de Carvalho, A., Costa, M. (2004). Transcriptional regulation of the murine Connexin40 promoter by cardiac factors Nkx2-5, GATA4 and Tbx5. Cardiovascular Research, 64(3), 402-411. [More Information]
  • Stennard, F., Costa, M., Elliott, D., Rankin, S., Haast, S., Lai, D., McDonald, L., Niederreither, K., Dolle, P., Bruneau, B., et al (2003). Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Developmental Biology, 262(2), 206-224.

2014

  • Sabri, A., Lai, D., D'Silva, A., Seeho, S., Kaur, J., Ng, C., Hyett, J. (2014). Differential Placental Gene Expression in Term Pregnancies Affected by Fetal Growth Restriction and Macrosomia. Fetal Diagnosis and Therapy: clinical advances and basic research, 36(2), 173-180. [More Information]
  • Lui, W., Zhang, X., Song, C., Bao, B., Lai, D., Mou, J., Jiang, T., Wang, N. (2014). Expression and characterization of a soluble VEGF receptor 2 protein. Cell & Bioscience, 4(1), 1-10. [More Information]
  • Mills, J., Sheahan, P., Lai, D., Kril, J., Janitz, M., Sutherland, G. (2014). The alternative splicing of the apolipoprotein E gene is unperturbed in the brains of Alzheimer's disease patients. Molecular Biology Reports, 41(10), 6365-6376. [More Information]

2013

  • Zhang, X., Lai, D., Bao, B., Hambly, B., Gillies, M. (2013). Triamcinolone Acetonide Inhibits p38MAPK Activation and Neuronal Apoptosis in Early Diabetic Retinopathy. Current Molecular Medicine, 13(6), 946-958. [More Information]

2012

  • Desbonnet, L., O'Tuathaigh, C., Clarke, G., O'Leary, C., Petit, E., Clarke, N., Tighe, O., Lai, D., Harvey, R., Cryan, J., et al (2012). Phenotypic effects of repeated psychosocial stress during adolescence in mice mutant for the schizophrenia risk gene neuregulin-1: a putative model of gene x environment interaction. Brain, Behavior, and Immunity, 26(4), 660-671. [More Information]

2011

  • Ju, Y., Liu, J., Lee, B., Lai, D., Woodcock, E., Lei, M., Cannell, M., Allen, D. (2011). Distribution and Functional Role of Inositol 1,4,5-trisphosphate Receptors in Mouse Sinoatrial Node. Circulation Research, 109(8), 848-857. [More Information]

2010

  • He, Z., Lai, D., Wakelin, L. (2010). [Co(III)(cyclen)Cl(2)]Cl is selectively cytotoxic to human leukaemia cells. European Journal of Pharmacology, 637(1-3), 11-15. [More Information]
  • Duffy, L., Cappas, E., Lai, D., Boucher, A., Karl, T. (2010). Cognition in Transmembrane Domain Neuregulin 1 Mutant Mice. Neuroscience, 170(3), 800-807. [More Information]
  • Walsh, J., Tighe, O., Lai, D., Harvey, R., Karayiorgou, M., Gogos, J., Waddington, J., O'Tuathaigh, C. (2010). Disruption of thermal nociceptive behaviour in mice mutant for the schizophrenia-associated genes NRG1, COMT and DISC1. Brain Research, 1348 (C), 114-119. [More Information]
  • Lai, D., Liu, X., Forrai, A., Wolstein, O., Michalicek, J., Ahmed, I., Garratt, A., Birchmeier, C., Zhou, M., Hartley, L., et al (2010). Neuregulin 1 Sustains the Gene Regulatory Network in Both Trabecular and Nontrabecular Myocardium. Circulation Research, 107(6), 715-727. [More Information]
  • O'Tuathaigh, C., Harte, M., O'Leary, C., O'Sullivan, G., Blau, C., Lai, D., Harvey, R., Tighe, O., Fagan, A., Kerskens, C., et al (2010). Schizophrenia-related endophenotypes in heterozygous neuregulin-1 'knockout' mice. European Journal of Neuroscience, 31(2), 349-358. [More Information]

2009

  • Tomiyama, K., O'Tuathaigh, C., O'Sullivan, G., Kinsella, A., Lai, D., Harvey, R., Tighe, O., Croke, D., Koshikawa, N., Waddington, J. (2009). Phenotype of spontaneous orofacial dyskinesia in neuregulin-1 ‘knockout’ mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33, 330-333. [More Information]

2008

  • O'Tuathaigh, C., O'Connor, A., O'Sullivan, G., Lai, D., Harvey, R., Croke, D., Waddington, J. (2008). Disruption to social dyadic interactions but not emotional/anxiety-related behaviour in mice with heterozygous ‘knockout’ of the schizophrenia risk gene neuregulin-1. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32(2), 462-466. [More Information]
  • Zhang, X., Bao, B., Lai, D., Rapkins, R., Gillies, M. (2008). Intravitreal Triamcinolone Acetonide Inhibits Breakdown of the Blood-Retinal Barrier through Differential Regulation of VEGF-A and its Receptors in Early Diabetic Rat Retinas. Diabetes, 57(4), 1026-1033. [More Information]

2007

  • Ju, Y., Chu, Y., Chaulet, H., Lai, D., Gervasio, O., Graham, R., Cannell, M., Allen, D. (2007). Store-operated Ca2+ influx and expression of TRPC genes in mouse sinoatrial node. Circulation Research, 100(11), 1605-1614. [More Information]

2006

  • Liu, X., Gu, X., Li, Z., Li, X., Li, H., Chang, J., Chen, P., Jin, J., Xi, B., Chen, D., Lai, D., et al (2006). Neuregulin-1/erbB-Activation Improves Cardiac Function and Survival in Models of Ischemic, Dilated, and Viral Cardiomyopathy. Journal of the American College of Cardiology, 48(7), 1438-1447. [More Information]
  • Kirk, E., Hyun, C., Thomson, P., Lai, D., Castro, M., Biben, C., Buckley, M., Martin, I., Moran, C., Harvey, R. (2006). Quantitative Trait Loci Modifying Cardiac Atrial Septal Morphology and Risk of Patent Foramen Ovale in the Mouse. Circulation Research, 98(5), 651-658. [More Information]

2005

  • Stennard, F., Costa, M., Lai, D., Biben, C., Furtado, M., Solloway, M., McCulley, D., Leimena, C., Preis, J., Dunwoodie, S., et al (2005). Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation. Development (Cambridge), 132(10), 2451-2462. [More Information]

2004

  • Linhares, V., Almeida, N., Menezes, D., Elliott, D., Lai, D., Beyer, E., Campos de Carvalho, A., Costa, M. (2004). Transcriptional regulation of the murine Connexin40 promoter by cardiac factors Nkx2-5, GATA4 and Tbx5. Cardiovascular Research, 64(3), 402-411. [More Information]

2003

  • Stennard, F., Costa, M., Elliott, D., Rankin, S., Haast, S., Lai, D., McDonald, L., Niederreither, K., Dolle, P., Bruneau, B., et al (2003). Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Developmental Biology, 262(2), 206-224.

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