Dr Kate Lee
Research | Current
I am a molecular biologist with research experience spanning the genetics of hypertension, proteomic and transcriptomic analysis, peptide therapeutics for diabetes, mass spec analysis of related peptide species, IGF-II, Islet function, insulin action models of diebetes and obesity. My expertise lie in proteomics and mass spec analysis as well as cell/tissue- and in-vivo peptide function assays and analysis of signalling pathways and protein interaction.
IGF-II related islet derived hormones. Beta cells in the Islets of Langerhans in the pancreas secrete not only insulin but also other peptide hormones that act synergistically to control blood glucose. These hormones include vesiculin and preptin, which were discovered by NZ researchers here at the University of Auckland. We are studying the function of these hormones both in their natural role as well as therapeutically. My interests extend to IGF-II biology in general which has received little attention so far in comparison to its well-studied relatives insulin and IGF-I. IGF-II is a very interesting peptide hormone that is highly related to insulin. Although primarily recognised as a fetal growth factor, IGF-II is also metabolically active and adult humans have high circulating levels of this hormone, although it is bound to other proteins in the blood preventing non-specific activity. Amazingly we really dont understad what role it plays in adult physiology.
Genetics of Diabetes. Tiny genetic differences between populations and indeed individuals are key drivers of disease. Complex diseases such as diabetes, obesity and CVD are essentially the product of environmental interactions with an individual's unique suite of genes. These diseases therefore have slightly different causes in different people although all resulting in the same pathology (high blood sugar or weight gain). This may be a slight variation in how well an individual produces important metabolic hormones in response to the right stimuli, how well their body responds to these hormones. Hormones control how an indvidual stores or uses the energy they consume, how much they absorb into the body and even how much food they eat and how often. Our research aims to investigate the effect of these genetic variations (identified in population-wide studies) on the elements described above and my own focus is on islet function and the function of Islet derived hormones.
Islet function. Islet cells and the hormones they secrete are crucial for maintenance of blood glucose and metabolic balance of the whole body. They act locally and distally and also synergistically with hormones secreted from the brain, gut and fat tissue to balance energy homeostasis through control of energy/nutrient consumption and storage as well as appetite and nutrient absorption. Along with a poor diet, derrangement of these systems leads to obesity, diabetes and cancer. The mechanisms surrounding how insulin secretory granules are stored, trafficked to the membrane and released from the cells are not well understood. Understanding these mechanisms is crucial as we can then understand how genetic variation in these systems leads to disease and ultimately how best to target therapeutics.
PhD - Sanaz Vakili
PhD - Shalinda Fernando
MSc - Thai Nguyen
Selected publications and creative works (Research Outputs)
- Dissanayake, W. C., Sorrenson, B., Lee, K. L., Barre, S., & Shepherd, P. R. (2020). α-catenin isoforms are regulated by glucose and involved in regulating insulin secretion in rat clonal β-cell models. The Biochemical journal, 477 (4), 763-772. 10.1042/bcj20190832
Other University of Auckland co-authors: Waruni Dissanayake, Brie Sorrenson
- 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, Peter Shepherd
- Lee, K. L., Aitken, J. F., Hsu, H.-L., Williams, G. M., Brimble, M. A., & Cooper, G. J. S. (2019). Glucoregulatory activity of vesiculin in insulin sensitive and resistant mice. Peptides, 116, 1-7. 10.1016/j.peptides.2019.04.011
Other University of Auckland co-authors: Jackie Aitken, Geoffrey Williams, Garth Cooper, Margaret Brimble
- 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. Journal of Biological Chemistry, 291 (50), 25888-25900. 10.1074/jbc.M116.758516
Other University of Auckland co-authors: Peter Shepherd, Brie Sorrenson, Waruni Dissanayake
- Williams, G. M., Lee, K., Li, X., Cooper, G. J., & Brimble, M. A. (2015). Replacement of the CysA7-CysB7 disulfide bond with a 1,2,3-triazole linker causes unfolding in insulin glargine. Organic and Biomolecular Chemistry, 13, 4059-4063. 10.1039/c5ob00160a
Other University of Auckland co-authors: Garth Cooper, Margaret Brimble, Geoffrey Williams
- Lee, K. L., Middleditch, M. J., Williams, G. M., Brimble, M. A., & Cooper, G. J. (2015). Using mass spectrometry to detect, differentiate, and semiquantitate closely related peptide hormones in complex milieu: Measurement of IGF-II and vesiculin. Endocrinology, 156 (3), 1194-1199. 10.1210/en.2014-1593
Other University of Auckland co-authors: Garth Cooper, Martin Middleditch, Margaret Brimble, Geoffrey Williams
- Williams, G. M., Cooper, G. J. S., Lee, K., Whiting, L., & Brimble, M. A. (2013). Synthesis of the IGF-II-like hormone vesiculin using regioselective formation of disulfide bonds. Organic & Biomolecular Chemistry, 11 (19), 3145-3150. 10.1039/C3OB40322J
Other University of Auckland co-authors: Geoffrey Williams, Garth Cooper, Margaret Brimble
- Lovell, M. J., Yasin, M., Lee, K. L., Cheung, K. K., Shintani, Y., Collino, M., ... Kapoor, A. (2010). Bone marrow mononuclear cells reduce myocardial reperfusion injury by activating the PI3K/Akt survival pathway. Atherosclerosis, 213 (1), 67-76. 10.1016/j.atherosclerosis.2010.07.045