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Lab personnel

  • Dr Megan Leask

    Assigning function to genetic variants associated with metabolic traits

  • Josiah Talosaga

    The role of JAZF1 in diabetes in Māori and Pacific people

Research interests

My research interests centre on the genetics of complex disease with particular expertise in the genetics of gout, chronic kidney disease and serum urate control.

I also carry out research working with Indigenous Māori and Pacific genetics.

I have a strong interest in addressing the unmet need for functional datasets (e.g. eQTL and metQTL) for these underrepresented groups.

Finally I work with non-coding genetic variation and using assays in zebrafish and cell-lines assign regulatory function

Research topics

  • Non-coding regulatory variation function in complex disease
  • Māori and Pacific-specific genetic variation

Current funding

  • 2023 Veteran Affairs Merit Award, Principal Investigator Lou Dell'Italia $700K USD
  • 2022 Diversity Supplement for NIH NIAMS R01, Functional and Integrative Omics of Recurrent Gout Flares, Principal Investigator Richard Reynolds $250K USD
  • 2022 HRC Project, The CALCRL receptor: A new genetic determinant of diabetic kidney disease in NZ, Principal Investigator, Alan Davidson $1.2M
  • 2022 Maurice Wilkins Centre Project Funding, Role of JAZF1 SNP in diabetes risk, Principal Investigator, Julia Horsfield $100K
  • 2021 Marsden Fund, Training natural language models to understand genomics and study gout in Māori and Pacific populations, Principal Investigator, Alex Gavryushkin $685K
  • 2020 HRC Emerging Researcher First Grant, Decoding GWAS to combat renal disease in Māori and Pacific peoples, Principal Investigator $300K

Previous funding

  • 2021 Maurice Wilkins Centre Category 2 Funding, Principal Investigator $10K
  • 2020 UoO Te Poutama Māori Collaboration Grant, Investigating links between bone mass, metabolic traits and appetite in Māori.  Principal Investigator, $10K
  • 2019 HRC Māori Career Development Award. Principal Investigator. $285K
  • 2016 Lottery Health Research Postdoctoral Fellowship Principal Investigator $75K

Teaching

  • PHSL 343 Cellular and Epithelial Physiology

Publications

Toomata, Z., Leask, M., Krishnan, M., Cadzow, M., Dalbeth, N., Stamp, L. K., … Merriman, T., Wilcox, P., … Murphy, R. (2023). Genetic testing for misclassified monogenic diabetes in Māori and Pacific peoples in Aotearoa New Zealand with early-onset type 2 diabetes. Frontiers in Endocrinology, 14, 1174699.  doi: 10.3389/fendo.2023.1174699

Moors, J., Krishnan, M., Sumpter, N., Takei, R., Bixley, M., Cadzow, M., Major, T. J., Phipps Green, A., Topless, R., Merriman, M., Rutledge, M., Morgan, B., … Stamp, L., Taumoepeau, M., … Wilcox, P., … McCormick, S., … Merriman, T. R., & Leask, M. (2023). A Polynesian-specific missense CETP variant alters the lipid profile. Human Genetics & Genomic Advances. Advance online publication. doi: 10.1016/j.xhgg.2023.100204

Brandon, R., Jiang, Y., Yeu, R. Q., Tweedie-Cullen, R., Smallman, K., Doherty, G., … Leask, M. P., Merriman, T. R., … Murphy, R. (2023). Stratified glucose-lowering response to vildagliptin and pioglitazone by obesity and hypertriglyceridemia in a randomized crossover trial. Frontiers in Endocrinology, 13, 1091421. doi: 10.3389/fendo.2022.1091421

Mandal, A. K., Leask, M. P., Sumpter, N. A., Choi, H. K., Merriman, T. R., & Mount, D. B. (2023). Genetic and physiological effects of insulin-like growth factor-1 (IGF-1) on human urate homeostasis. Journal of the American Society of Nephrology. Advance online publication. doi: 10.1681/ASN.0000000000000054

Sumpter, N. A., Takei, R., Cadzow, M., Topless, R. K. G., Phipps-Green, A. J., Murphy, R., … Major, T. J., Stamp, L. K., … Leask, M. P., … Merriman, T. R. (2023). Association of gout polygenic risk score with age at disease onset and tophaceous disease in European and Polynesian men with gout. Arthritis & Rheumatology, 75(5), 816-825. doi: 10.1002/art.42393

Brandon, R., Jiang, Y., Yeu, R. Q., Tweedie-Cullen, R., Smallman, K., Doherty, G., … Leask, M., Merriman, T. R., … Paul, R., & Murphy, R. (2022, August). Precision medicine in diabetes: Type 2 diabetes medication Which One is Right Here? (WORTH) study. Verbal presentation at the Metabolic & Cardiovascular Disease Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

Chang, H. H. G., Leask, M. P., Kallingappa, P. K., Merry, T. L., Hotu, C., de Zoysa, J., … Fronius, M., … Hay, D. L., Merriman, T. R., & Davidson, A. J. (2022, August). The CALCRL receptor: A potential new genetic determinant of diabetic kidney disease in NZ. Verbal presentation at the Metabolic & Cardiovascular Disease Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

Lupi, A. S., Sumpter, N. A., Leask, M. P., O'Sullivan, J., Fadason, T., de los Campos, G., Merriman, T. R., … Vazquez, A. I. (2022). Local genetic covariance between serum urate and kidney function estimated with Bayesian multitrait models. Genes Genomes Genetics, 12(9), jkac158.  doi: 10.1093/g3journal/jkac158

Sumpter, N. A., Takei, R., Leask, M. P., Reynolds, R. J., & Merriman, T. R. (2022). Genetic association studies of the progression from hyperuricaemia to gout. Rheumatology, 61, e139-e140.  doi: 10.1093/rheumatology/keac011

Brandon, R., Jiang, Y., Yeu, R. Q., Tweedie-Cullen, R., Smallman, K., Doherty, G., … Leask, M., Merriman, T. R., … Murphy, R. (2022). Randomised cross-over trial of vidagliptin and pioglitazone as add-on therapy in patients with type 2 diabetes: Predicting Which One is Righ Here (WORTH) Study: Predicting type 2 diabetes medication response. Proceedings of the New Zealand Society for the Study of Diabetes (NZSSD) Annual Scientific Meeting. (pp. 30).  Retrieved from https://www.ivvy.com.au/event/NZSSD22/welcome.html

Wang, K., Cadzow, M., Bixley, M., Leask, M. P., Merriman, M. E., Yang, Q., … Takei, R., Phipps-Green, A., Major, T. J., Topless, R., … Stamp, L. K., … Merriman, T. R. (2022). A Polynesian-specific copy number variant encompassing the MICA gene associates with gout. Human Molecular Genetics, 31(21), 3757-3768.  doi: 10.1093/hmg/ddac094

Morice, M., Bixley, M., Cadzow, M., Major, T., Phipps-Green, A., Topless, R., Merriman, M., Merriman, T. R., Leask, M., & Horsfield, J. (2021). Replication of a Māori and Pacific-specific T2D-risk variant within JAZF1.   New Zealand Medical Journal, 134(1547), (pp. 142).  Retrieved from https://www.nzma.org.nz/journal

Leask, M., Carleton, C., Leeke, B., Newman, T., Antoun, J., Farella, M., & Horsfield, J. (2021). Riboceine rescues auranofin-induced craniofacial defects in zebrafish. Antioxidants, 10, 1964.  doi: 10.3390/antiox10121964

Leask, M. P., & Merriman, T. R. (2021). The genetic basis of urate control and gout: Insights into molecular pathogenesis from follow-up study of genome-wide association study loci. Best Practice & Research: Clinical Rheumatology, 35, 101721.  doi: 10.1016/j.berh.2021.101721

Mandal, A. K., Leask, M. P., Estiverne, C., Choi, H. K., Merriman, T. R., & Mount, D. B. (2021). Genetic and physiological effects of insulin on human urate homeostasis. Frontiers in Physiology, 12, 713710.  doi: 10.3389/fphys.2021.713710

Leask, M., Lovegrove, M., Romeril, A., Duncan, E., & Dearden, P. (2021). Evolution and genomic organization of the insect sHSP gene cluster and coordinate regulation in phenotypic plasticity. BMC Ecology & Evolution, 21, 154.  doi: 10.1186/s12862-021-01885-8

Topless, R. K., Phipps-Green, A., Leask, M., Dalbeth, N., Stamp, L. K., Robinson, P. C., & Merriman, T. R. (2021). Gout, rheumatoid arthritis, and the risk of death related to coronavirus disease 2019: An analysis of the UK Biobank. ACR Open Rheumatology, 3(5), 333-340.  doi: 10.1002/acr2.11252

Sumpter, N., Lupi, A., Leask, M., Merriman, T., Vazquez, A., & Reynolds, R. (2020). Genomic regions jointly associated with eGFR and serum urate: Implications for shared genetic etiology of hyperuricemia and chronic kidney disease.   Arthritis & Rheumatology, 72(Suppl. 10), 0661. [Abstract]

Leask, M., Dalbeth, N., Stamp, L., Merriman, T., Phipps-Green, A., Topless, R., Boocock, J., … Leaupepe, K., & Stahl, E. (2020). Polynesian-specific gout-associated frameshift variant in PRPSAP1.   Arthritis & Rheumatology, 72(Suppl. 10), 0659. [Abstract]

Leask, M. P., Sumpter, N. A., Lupi, A. S., Vazquez, A. I., Reynolds, R. J., Mount, D. B., & Merriman, T. R. (2020). The shared genetic basis of hyperuricemia, gout, and kidney function. Seminars in Nephrology, 40(6), 586-599.  doi: 10.1016/j.semnephrol.2020.12.002

Moors, J., Leask, M., Dalbeth, N., Stamp, L., Hindmarsh, J. H., & Merriman, T. (2020). Novel CETP variant associates with increased HDL and low LDL in Polynesian populations. In A. Finigan, P. Vakaoti, R. Richards, M. Schaaf, M. Colombo, M. Taumoepeau & L. Moata'ane (Eds.), Proceedings of the Pacific Postgraduate Symposium: Pacific Voices XVII. (pp. 33). Dunedin, New Zealand: Pacific Islands Centre, University of Otago. Retrieved from https://www.otago.ac.nz/pacific

Duncan, E. J., Leask, M. P., & Dearden, P. K. (2020). Genome architecture facilitates phenotypic plasticity in the honeybee (Apis mellifera). Molecular Biology & Evolution, 37(7), 1964-1978.  doi: 10.1093/molbev/msaa057

Boocock, J., Leask, M., Okada, Y., Asian Genetic Epidemiology Network (AGEN) Consortium, Matsuo, H., Shi, Y., … Cadzow, M., Gosling, A. L., Major, T. J., Horsfield, J. A., … Merriman, T. R. (2020). Genomic dissection of 43 serum urate-associated loci provides multiple insights into molecular mechanisms of urate control. Human Molecular Genetics, 29(6), 923-943.  doi: 10.1093/hmg/ddaa013

Moors, J., Leask, M., Dalbeth, N., Stamp, L., Hindmarsh, J. H., & Merriman, T. (2019). Novel CETP variant associates with increased HDL and low LDL in Polynesian populations. In A. Finigan, P. Vakaoti, R. Richards & M. Schaaf (Eds.), Proceedings of the Pacific Postgraduate Symposium: Pacific Voices XVI. (pp. 23). Dunedin, New Zealand: The Pacific Islands Centre, University of Otago.  Retrieved from https://www.otago.ac.nz/pacific

Moors, J., Leask, M., Dalbeth, N., Stamp, L., Hindmarsh, J. H., & Merriman, T. (2019). Pacific-specific CETP genetic variant associates with increased HDL and low LDL in Polynesian populations.   Diabetologia, 62(Suppl. 1), (pp. S574-S575). [Abstract]

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