Professor Peter Shepherd
I moved back to New Zealand from University College London in Sept 2004 and my research continues to be in the broad area of signal transduction with a particular focus on PI 3-kinase and Wnt signaling pathways.The diseases we focus on are type-2 diabetes, cancer and schizophrenia as defects in signal transduction are a feature of all these diseases. Translational research is also an important focus and Pathway Therapeutics and Symansis are two companies that have spun out from the lab.
- Deputy Director, Maurice Wilkins Centre for Molecular Biodiscovery (www.mauricewilkinscentre.org)
- Chair of Queenstown Molecular Biology Meetings Society (www.qmb.org.nz)
Research | Current
The lab has been directly involved in several drug discovery programmes in collaboration with the Auckland Cancer Society Research Centre (ACSRC). These resulted in the devlopment of the PI 3-kinase inhibitor PWT33597 and its advancement to phase-1 clnical trial as an anticancer agent. Several PI 3-kinase drug discovery projects are ongoing aimed at developing second generation inhibitors, including one in collaboration with the Chinese National Centre for Drug Screening. We are also involved in drug development programmes on targets in the immunotherapy space.
In recent years we have genotyped and functionally characterised a panel of 102 primary melanoma cell lines developed at the ACSRC. The aim is to understand the links between genotype, cell signalling pathway activation and the response to drugs so as to be able to identify new mechanisms that predict drug resistance and to be able to test novel drug combinations in vitro against a wide range of genotype combinations. Signalling mechanisms investigated in depth include the PI 3-kinase pathway, the VEGF pathway, growth factor receptors, factors affecting response to MEK and BRaf inhibitors, the role of cannabinoid receptors, the role of growth hormone receptors and also the mechanisms by which statins impact on melanoma. We are currently starting work to characterise a similar panel of glioblastoma cell lines.
Mechanisms regulating hormone secretion
We have identified a crucial role for beta-catenin in the regulation of insulin and neuropeptide hormone secretion. Work stemming from this has shown levels of beta-catenin are regulated by nutrient levels indicating that this is a novel mechanisms by which nutrients can modulate the level of hormone secretion in some cells. As part of this work we are using human induced pluripotent stem cells to develop human beta-cell models with specific SNPs known to affect both insulin secretion and beta-catenin function. This work involves collaborations with Prof Dave Grattan at Otago University, A/Prof Alan Davidson and Dr Tersea Holm at UoA and in Sydney with Dr Greg Smith at UNSW and Dr Will Hughes at the Garvan Institute.
Teaching | Current
Areas of expertise
Role of cell signalling pathways
Diabetes and Obesity
Selected publications and creative works (Research Outputs)
- Sorrenson, B., Cognard, E., Lee, K. L., Dissanayake, W. C., Fu, Y., Han, W., ... Shepherd, P. R. (2016). A Critical Role for β-Catenin in Modulating Levels of Insulin Secretion from β-Cells by Regulating Actin Cytoskeleton and Insulin Vesicle Localization. The Journal of biological chemistry, 291 (50), 25888-25900. 10.1074/jbc.m116.758516
Other University of Auckland co-authors: Brie Sorrenson, Kate Lee
- Jones, A. M., Ferguson, P., Gardner, J., Rooker, S., Sutton, T., Ahn, A., ... Emanuel, P. (2016). NRAS and EPHB6 mutation rates differ in metastatic melanomas of patients in the North Island versus South Island of New Zealand. Oncotarget, 7 (27), 41017-41030. 10.18632/oncotarget.9351
- Jones, N. M., Rowe, M. R., Shepherd, P. R., & McConnell, M. J. (2016). Targeted inhibition of dominant PI3-kinase catalytic isoforms increase expression of stem cell genes in glioblastoma cancer stem cell models. International journal of oncology, 49 (1), 207-216. 10.3892/ijo.2016.3510
- Chowdhury, M. K. H., Wu, L. E., Coleman, J. L. J., Smith, N. J., Morris, M. J., Shepherd, P. R., & Smith, G. C. (2016). Niclosamide blocks glucagon phosphorylation of Ser552 on β-catenin in primary rat hepatocytes via PKA signalling. The Biochemical journal, 473 (9), 1247-1255. 10.1042/bcj20160121
- Marshall, A. J., Lill, C. L., Chao, M., Kolekar, S. V., Lee, W.-J., Marshall, E. S., ... Flanagan, J. U. (2015). Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: synthesis, biological evaluation and molecular modelling. Bioorganic & medicinal chemistry, 23 (13), 3796-3808. 10.1016/j.bmc.2015.03.073
Other University of Auckland co-authors: Jack Flanagan, Bill Denny, Gordon Rewcastle, Bruce Baguley
- Chowdhury, M. K. H., Montgomery, M. K., Morris, M. J., Cognard, E., Shepherd, P. R., & Smith, G. C. (2015). Glucagon phosphorylates serine 552 of β-catenin leading to increased expression of cyclin D1 and c-Myc in the isolated rat liver. Archives of physiology and biochemistry, 121 (3), 88-96. 10.3109/13813455.2015.1048693
- Sweetlove, M., Wrightson, E., Kolekar, S., Rewcastle, G. W., Baguley, B. C., Shepherd, P. R., & Jamieson, S. M. F. (2015). Inhibitors of pan-PI3K Signaling Synergize with BRAF or MEK Inhibitors to Prevent BRAF-Mutant Melanoma Cell Growth. Frontiers in oncology, 510.3389/fonc.2015.00135
Other University of Auckland co-authors: Gordon Rewcastle, Bruce Baguley, Stephen Jamieson
- Smith, G. C., McEwen, H., Steinberg, J. D., & Shepherd, P. R. (2014). The activation of the Akt/PKB signalling pathway in the brains of clozapine-exposed rats is linked to hyperinsulinemia and not a direct drug effect. Psychopharmacology (Berl), 231 (23), 4553-4560. 10.1007/s00213-014-3608-0