Professor Peter Shepherd
BSc(Hons) Massey , PhD Massey
After graduating from Massey University I undertook post doctoral research at Harvard Medical School and the University of Cambridge before gaining a tenured position at University College London. I moved back to New Zealand from University College London in 2004 and my research continues to be in the broad area of signal transduction with a particular focus on type-2 diabetes and cancer. The lab encourages a collaborative approach with research groups across New Zealand and overseas to make the most of our research programmes. The main research current areas are (i) identifying new combinations of old drugs targeting signal transduction pathways to get improved efficacy in treating cancer, (ii) developing new drugs targeting CSF1R to improve the efficacy of immunotherapies for cancer (iii) investigating the role of ß-catenin in mechanisms controlling the secretion of insulin from ß-cells and (iv) understanding how genetic factors contribute to the increased risk of metabolic diseases in Māori and Pacific peoples.
The lab also has a strong focus on scientific outreach. One avenue for this is understanding how we can link our research with high schools to make our research have impact on science education in this country. The research part of this is the "Sugar in Schools" study which is a study where students and teachers do the experiment themsleves using a hydrogen breathalyser to assess levels of fructose intolerance in new Zealand school children. This is designed to prvde a real world investigation that kids can do on themsleves and that will engage them with science an health literacy. This is linked to educational material about sugar and metabolic diseases that fits with the NZ NCEA curriculim. Another important area of outreach has been in development of research collaborations and partnerships with Māori communities.
Translational research is also an important focus and Pathway Therapeutics and Symansis are two companies that have spun out from the lab and clnical trials are in development in the cancer and diabetes spaces.
- 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 pogramme develping inhibitors of CSF1 receptor as a strategy to improve the efficacy of cancer immunotherapies. This work also involves collaboration with researchers at the Malaghan Institute and is funded by the Health Research Council and the Maurice Wilkins Centre.
In recent years we have genotyped and functionally characterised a panel of 102 primary melanoma cell lines and 30+ primary glioblastoma cell lines developed at Uinversity of Auckland 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. This work has identified a novel combination of drugs with high efficacy in preclnical studies and we are now moving to develop a human clnical trial with the Auckland Hospital Phase-1 clnical trials centre. The work is funded by the Health Research Council of NZ project grants, the Cancer Society and the Gut Cancer Foundation. It involves collaborations with UoA researchers Prof Bruce Baguley, Dr Francis Hunterr, Dr Jo Perry and Prof Cris Print. Phd students associated with this work are Vahid Seyfodin, Khanh Tran and Karla Sousa.
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. Posdoctoral Fellows Dr Kate Lee and Dr Waruni Dissanyake and PhD student Jake Oh are associated with this project. The work is funded by the Maurice Wilkins Centre and previously by the Health Research Council.
Genetic factors affecting metabolic disease risk
This project involves deep phenotyping studies combined with analysis of gene variants to understand how genetic factors might contribute to the increased risk of developing metabolic diseases in Maori and Pacific peoples and to use this information to develop better prevention or treatment strategies. It involves collaborations with the Moko Foundation (Waharoa ki te Toi Research Centre in Kaitaia) and Ngati Porou Hauora (Te Rangawairua o Paratene Ngata Research Centre in Te Puia Springs) as well as Prof Tony Merriman and Dave Grattan in Otago and A/Prof Rinki Murphy and Troy Merry in Auckland. Kate Lee is also assisting on this project and Shalinda Fernando, Sanaz Vakili and Hannah Burden are PhD students on this project. The work is funded by and HRC programme grant and by the Maurice Wilkins Centre.
Teaching | Current
Fellow of the Royal Society of New Zealand
Callaghan Medal of Royal Society of NZ
Adjunct Professor, Fudan University, Shanghai
CLNZ NZ Educational Book award for High School Biology Level 2 NCEA text book co-authored with Rachel Heeney
Areas of expertise
Role of cell signalling pathways
Diabetes and Obesity
Convenor of Queenstown Research Week
Selected publications and creative works (Research Outputs)
- Buchanan, C. M., Lee, K. L., & Shepherd, P. R. (2019). For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors. Biomolecules, 9 (9).10.3390/biom9090402
Other University of Auckland co-authors: Christina Buchanan, Kate Lee
- Dissanayake, W. C., Sorrenson, B., Cognard, E., Hughes, W. E., & Shepherd, P. R. (2018). β-catenin is important for the development of an insulin responsive pool of GLUT4 glucose transporters in 3T3-L1 adipocytes. Experimental cell research, 366 (1), 49-54. 10.1016/j.yexcr.2018.03.011
Other University of Auckland co-authors: Brie Sorrenson, Waruni Dissanayake
- Dissanayake, W. C., Sorrenson, B., & Shepherd, P. R. (2018). The role of adherens junction proteins in the regulation of insulin secretion. Bioscience reports, 38 (2).10.1042/bsr20170989
Other University of Auckland co-authors: Brie Sorrenson, Waruni Dissanayake
- Tran, B., Hunter, F., Jamieson, S., Kolekar, S., Li, D., Kakadiya, P., ... Bohlander, S. K. (2017). Preclinical efficacy and sensitivity determinants of statins in molecularly-defined models of melanoma. Paper presented at New Zealand Society for Oncology Conference, Auckland, New Zealand.
Other University of Auckland co-authors: Francis Hunter, Khanh Tran, Stephen Jamieson, Sharada Kolekar, Purvi Kakadiya, Cristin Print, Stefan Bohlander
- Rewcastle, G. W., Kolekar, S., Buchanan, C. M., Gamage, S. A., Giddens, A. C., Tsang, K. Y., ... Smith, G. C. (2017). Biological characterization of SN32976, a selective inhibitor of PI3K and mTOR with preferential activity to PI3Kα, in comparison to established pan PI3K inhibitors. Oncotarget, 8 (29), 47725-47740. 10.18632/oncotarget.17730
Other University of Auckland co-authors: Gordon Rewcastle, Christina Buchanan, Swarna Gamage, Bill Denny, Stephen Jamieson, Anna Giddens, Woo Lee
- Gong, G. Q., Kendall, J. D., Dickson, J. M., Rewcastle, G. W., Buchanan, C. M., Denny, W. A., ... Flanagan, J. U. (2017). Combining properties of different classes of PI3Kα inhibitors to understand the molecular features that confer selectivity. Biochemical Journal, 474 (13), 2261-2276. 10.1042/BCJ20161098
Other University of Auckland co-authors: Gordon Rewcastle, James Dickson, Christina Buchanan, Bill Denny, Jack Flanagan
- Kendall, J., Giddens, A., Tsang, K., Marshall, E., Lill, C., Lee, W.-J., ... Yu, S. (2017). Novel pyrazolo[1,5-a]pyridines with improved aqueous solubility as p110α-selective PI3 kinase inhibitors. Bioorganic and Medicinal Chemistry Letters, 27 (2), 187-190. 10.1016/j.bmcl.2016.11.078
Other University of Auckland co-authors: Bill Denny, Christina Buchanan, Gordon Rewcastle, Stephen Jamieson, Anna Giddens, Woo Lee
- Chowdhury, M. K. H., Turner, N., Bentley, N. L., Das, A., Wu, L. E., Bustamante, S., ... Shepherd, P. R. (2017). Niclosamide reduces glucagon sensitivity via hepatic PKA inhibition in obese mice: Implications for glucose metabolism improvements in type 2 diabetes. Scientific Reports, 710.1038/srep40159