Zane Andrews, PhD - Lab Head
Australian Research Council Future Fellow
Address
Department of Physiology
Building 13F
Monash University
VIC 3800, Australia
Located: Room F227, Building 13F (Physiology)
Campus
Clayton
Tel: +61 3 990 58165
Fax: +61 3 990 52547
Email: Zane.Andrews@monash.edu
Staff/students:
Sarah Lockie (Postdoctoral Fellow)
Romana Stark (Postdoctoral Fellow)
Vanessa Valgas (Postdoctoral Fellow)
Moyra Lemus (research assistant)
Alex Reichenbach (research assistant)
Jackie Bayliss (PhD student)
Minh Deo (Honours Student)
Qunli Wu (Visiting trainee fellow)
Biography
Dr Andrews received his PhD in New Zealand at the University of Otago in 2003 and has 13 years experience in the field of neuroendocrinology and neuroscience. From there, he went on to do postdoctoral training at Yale University, New Haven, Connecticut, USA (2004-2008) where he was awarded a prestigious New Zealand Foundation for Research Science and Technology Postdoctoral Fellowship. He has published in the world’s leading journals including Nature, Cell Metabolism, Neuron, Journal of Clinical Investigation and the Journal of Neuroscience. His work has attracted significant public interest, including invitation to write for Scientific Amercian and Australasian Science. Dr Andrews came to Monash University late in 2008 as a Monash Fellow and has started to establish his own research program. In 2011 he became an Australian Research Council Future Fellow. He uses a combination of genetic mouse models (global knockouts, conditional knockouts using the cre/lox system) and in vivo physiology to probe questions about how metabolic status affects appetite, body weight, glucose homeostasis, neuronal metabolism and neurodegeneration.
Research Overview
We use novel genetic and physiological in vivo models as well as in vitro models to investigate how metabolic status regulates appetite, body weight, glucose homeostasis and hormone secretion with a particular interest in mitochondrial mechanisms. We are particularly interested in mitochondrial proteins that act as nutrient sensors or as regulators of cell bioenergetic processes and how these affect neural circuits controlling appetite and energy metabolism. We also focus on mitochondrial mechanisms, again acting as nutrient sensors or as regulators of cell metabolism, that control neurodegeneration and brain disease.
We believe these mitochondrial mechanisms will have broad implications on the function of all neurons, not just those pertaining to appetite and degeneration.
The two fundamental questions explored in this lab are;
1) what are neural mechanisms regulating food intake and weight, and how is this regulated by metabolic hormones and/or different physiological states?
2) how do metabolic hormones and/or different physiological states influence neurodegenerative processes? We use and develop novel transgenic mouse lines using the cre/lox system to explore the physiological relevance of these questions
The lab has recently focused on the hormone ghrelin, as it is an important metabolic hormone secreted from the stomach during negative energy balance (a metabolic state producing hunger) that drives food intake and body weight gain. Ghrelin-induced food intake is primarily mediated via hypothalamic feeding circuits and current research in the lab focuses on the mechanisms regulating hypothalamic responsiveness to peripheral metabolic hormones such as ghrelin. Recently, we reported that ghrelin activates mitochondrial function, which plays an integral role in maintaining hypothalamic responsiveness to circulating ghrelin. Understanding the interactions between metabolic hormones and hypothalamic mitochondrial function is a core focus of the lab. Current projects involve selectively knocking out mitochondrial proteins in feeding neurons of the hypothalamus and examining the subsequent metabolic phenotype using a range of techniques that including neuroanatomy, molecular biology and in vivo physiology and animal behaviour. In addition, metabolic hormones such as ghrelin act outside the hypothalamus in other regions of the brain including the hippocampus and midbrain. Interestingly, ghrelin produces similar mitochondrial changes in the midbrain that confers neuroprotection in models of Parkinson’s disease. Understanding exactly how ghrelin regulates mitochondrial function and neuroprotection in models of Parkinson’s disease is the second core focus of the lab. Studies in this field open the door to an unexplored avenue of metabolic neuroscience pertaining to the regulation of neurodegeneration by hormones that control energy metabolism and body weight regulation. The importance of this emerging field is underscored by recent epidemiological reports showing that obesity, diabetes and elevated body mass index predispose to future risk of Parkinson’s disease, suggesting that perturbations in energy metabolism resulting in obesity not only affect pathological conditions such as cancer, diabetes and heart disease, but also neurodegeneration. Moreover, the obesity epidemic has exploded in recent years and given that neurological disease takes many years to manifest into observable symptoms, it is reasonable to assume that an increase in the prevalence of neurological disease as the result of profound long-term obesity may occur in the near future.
Current Projects
PhD scholarships are currently available to outstanding and motivated students. These projects will examine the neural control of appetite and body weight using state-of-the-art transgenic mice (using the cre/lox system) generated at Monash University by Dr Zane Andrews.
1) These projects will examine how AgRP or POMC neurons in the hypothalamus, at the base regulate appetite, body weight and glucose homeostasis. We have generated novel transgenic mouse lines with selectively deleted mitochondrial genes only in hypothalamic AgRP or POMC neurons. By examining the physiological outcome, we hope to understand how mitochondrial metabolism in these brain cells affects appetite, and predisposes individuals to develop obesity and diabetes.
2) We are examining how mitochondrial proteins in dopamine neurons control degeneration. This project is directly aimed at understanding the pathogenesis of dopamine neurons in Parkinson’s disease.
3) We are also interested in examining how mitochondrial proteins in dopamine neurons control rewarding and motivational aspects of food intake. Numerous studies show that human obesity is not caused by the need to eat (ie to maintain homeostasis), but rather by the desire to eat (ie because it makes us feel good). Indeed, dopaminergic systems within the brain play a critical role to mediate the reward nature of food intake, particularly high fat, energy dense food. By deleting mitochondrial genes that acts as both nutrient sensors and bioenergetic regulators, we hope to identify the novel mechanisms controlling our desire to eat fatty foods.
4) Numerous studies show that energy levels, conveyed by plasma glucose, fats or protein, control the secretion of gut hormones regulating appetite such as ghrelin, GLP1, CCK and PYY. However, the molecular mechanisms that sense fluctuations in energy balance and modify hormonal secretion accordingly, are completely unknown. We are examining mitochondrial mechanisms in gut hormone-secreting cells to identify new targets regulating hormone secretion. The studies will help understand mechanisms regulating satiety hormones with the hope to develop novel drugs that suppress appetite, and prevent obesity and diabetes.
PhD applicants should have a MSc, 1st class honours or significant laboratory experience
All applicants and inquires should be sent to Dr Zane Andrews
Publications (since 2005)
Publications - Book Chapters
Reichenbach A, Stark R, Andrews ZB. Hypothalamic control of food intake and energy metabolism. In: The Human Hypothalamus: Anantomy, Functions and Disease. Editor: Bertalan Dudas, Publisher: NOVA Science Publishers, Inc ISBN:978-1-62081-806-0 2013. 2013 Chapter 9, 247-282.
Enriori PJ, Andrews ZB, Cowley MA. Ghrelin: Neuropeptide regulator of metabolism. Ghrelin in Health and Disease. Roy Smith and Michael Thorner (Eds.) 2012 Chapter 6, 111-130 Springer Publishing.
Bayliss J, Stark R, Reichenbach A and Andrews ZB. Gut Hormones Restrict Neurodegeneration in Parkinson’s Disease, Advanced Understanding of Neurodegenerative Diseases, 2011 Chapter 12;269-284. Raymond Chuen-Chung Chang (Ed.), ISBN: 978-953-307-529-7, InTech, Available from: http://www.intechopen.com/articles/show/title/gut-hormones-restrict-neurodegeneration-in-parkinson-s-disease
Publications - Journal Articles
Kenny R, Cai G, Bayliss JA, Clarke M, Choo YL, Miller AA, Andrews ZB, and Spencer SJ. Endogenous ghrelin's role in hippocampal neuroprotection after global cerebral ischemia: does endogenous ghrelin protect against global stroke? American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. Accepted and in press
Spencer SJ, Miller AA, Andrews ZB. The role of ghrelin in neuroprotection after ischemic brain injury. Brain Science 2013 3:344-359
Bayliss JA, Andrews ZB. Ghrelin is neuroprotective in Parkinson's Disease; molecular mechanisms of metabolic neuroprotection. Therapeutic Advances in Endocrinology and Metabolism. 2013 4(1):25-36
Briggs DI, Lockie SH, Wu Q, Lemus MB, Stark R, Andrews ZB. Calorie-Restricted Weight Loss Reverses High-Fat Diet-Induced Ghrelin Resistance, Which Contributes to Rebound Weight Gain in a Ghrelin-Dependent Manner. Endocrinology. 2013 Feb 154(2):709-17
Stark R, Ashley SE, Andrews ZB. AMPK and the neuroendocrine regulation of appetite and energy expenditure. Molecular and Cellular Endocrinology 2013 366:215-223
Gyengesi E, Paxinos G, Andrews ZB. Oxidative stress in the hypothalamus: the importance of calcium signaling and mitochondrial ROS in body weight regulation. Current Neuropharmacology. 2012 10(4):344-353.
Clarke SD, Lee K, Andrews ZB, Bischof R, Fahri F, Evans RG, Clarke IJ, Henry BA. Postprandial heat production in skeletal muscle is associated with altered mitochondrial function and altered futile calcium cycling. Am J Physiol Regul Integr Comp Physiol. 2012 Nov 15;303(10):R1071-9.
Reichenbach A, Steyn FJ, Sleeman MW, Andrews ZB. Ghrelin receptor expression and colocalization with anterior pituitary hormones using a GHSR-GFP mouse line. Endocrinology. 2012 153(11):5452-66. (IF=4.49)
Spencer SJ, Xu L, Clarke MA, Lemus M, Reichenbach A, Geenen B, Kozicz T, Andrews ZB. Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress. Biological Psychiatry 2012, Sep 15;72(6):457-65.
Loh K, Fukushima A, Zhang X, Galic S, Briggs D, Enriori PJ, Simonds S, Wiede F, Reichenbach A, Hauser C, Sims NA, Bence KK, Zhang S, Zhang ZY, Kahn BB, Neel BG, Andrews ZB, Cowley MA, Tiganis T. Elevated Hypothalamic TCPTP in Obesity Contributes to Cellular Leptin Resistance. Cell Metabolism. 2011 Nov 2;14(5):684-99.
Furness JB, Hunne B, Matsuda N, Yin L, Russo D, Kato I, Fujimiya M, Patterson M, McLeod J, Andrews ZB, Bron R. Investigation of the presence of ghrelin in the central nervous system of the rat and mouse. Neuroscience, 2011 Oct 13;193:1-9.
Andrews ZB. Central mechanisms involved in the orexigenic actions of ghrelin. Peptides, 2011 Nov;32(11):2248-55.
Henry BA, Andrews ZB, Rao A, Clarke IJ. Central leptin activates mitochondrial function and increases heat production in skeletal muscle. Endocrinology, 2011 Jul;152(7):2609-18
Briggs DI, Andrews ZB. A recent update on the role of ghrelin in glucose homeostasis. Current Diabetes Reviews, 2011; 7(3):201-7
Briggs DI, Lemus M, Kua E, Andrews ZB. Diet-induced obesity attenuates fasting-induced hyperphagia. Journal of Neuroendocrinology, 2011; 23(7):620-6
Horvath TL, Erion DM, Elsworth JD, Roth RH, Shulman GI and Andrews ZB. GPA protects the nigrostriatal dopamine system by enhancing mitochondrial function. Neurobiology of Disease, 2011; 43(1):152-62.
Pigment epithelium-derived factor regulates lipid metabolism via adipose triglyceride lipase. Borg ML, Andrews ZB, Duh EJ, Zechner R, Meikle PJ, Watt MJ. Diabetes, 2011 May; 60(5):1458-66
Briggs DI, Andrews ZB. Metabolic status mediates the neuroendocrine actions of ghrelin. Neuroendocrinology. 2011; 93(1):48-57
Andrews ZB. The extra-hypothalamic actions of ghrelin on neuronal function. Trends in Neuroscience 2011, 34(1):31-40
Wolff EF, Gao XB, Yao KV, Andrews ZB, Du H, Elsworth JD, Tay1lor HS. Endometrial stem cell transplantation restores dopamine production in a parkinson's disease model. Journal of Cellular and Molecular Medicine, 2011 Apr 15(4):747-55.
Briggs DI, Enriori PJ, Lemus MB, Cowley MA, Andrews ZB. Diet-induced obesity causes ghrelin resistance in NPY/AgRP neurons. Endocrinology, 2010 151(10): 4745-4755
Andrews ZB*, Erion DM, Beiler R, Choi CS, Shulman GI, Horvath TL*. Uncoupling protein-2 decreases the lipogenic actions of ghrelin. Endocrinology 2010 151(5):2078-86. * Corresponding authors.
Andrews ZB. UCP2 and the potential link between longevity and metabolism. Current Aging Science 2010 3(2):102-12
Andrews ZB, Erion DM, Beiler R, Liu ZW, Abizaid A, Zigman J, Elsworth JD, Savitt JM, DiMarchi R, Tschoep M, Roth R, Xiao-Bing Gao, Horvath TL. Ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. Journal of neuroscience, 2009 29(45):14057-14065
This week in the journal feature: http://www.jneurosci.org/cgi/content/full/29/45/i
Feature on MJ Foundation website: http://www.pdonlineresearch.org/news/2009-11/10/metabolic-hormone-ghrelin-protects-against-mptp-induced-toxicity
Andrews ZB*, Horvath TL*. Uncoupling Protein-2 mediates lifespan in mice by regulating reactive oxygen species. American Journal of Physiology Endocrinology and metabolism, 2009 Apr 296(4):E621-7. * Corresponding author.
Editorial focus: http://ajpendo.physiology.org/cgi/content/full/296/4/E619
Andrews ZB, Overeating as we age. Australasian Science, 2009 30(2) 14-16.
Horvath TL, Andrews ZB, Diano S. Fuel utilization by hypothalamic neurons: roles for ROS. Trends in Endocrinology and Metabolism, 2009 20(2):78-87
Dietrich MO, Andrews ZB, Horvath, TL. Exercise-induced synaptogenesis in the hippocampus is dependent on UCP2-regulated mitochondrial adaption. Journal of Neuroscience, 2008 Oct 15;28(42):10766-71.
Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL Diano S. Uncoupling protein-2 mediates ghrelin’s action on NPY/AgRP neurons. Nature, 2008 454(7206): 846-51.
Andrews ZB and Horvath TL. Why calorie taste delicious: eating and the brain. Scientific American, 2008 Sept 30 invited contribution.
http://www.sciam.com/article.cfm?id=why-calories-are-delicious#comments.
Andrews ZB, Horvath TL. Tastleless food reward. Neuron 2008 57 806-808.
Coppola A, Zhong Wu L, Andrews ZB, Roy MC, Gao Q, Pinto S, Friedman JM, Galton V, Ricquier D, Richard D, Horvath TL, Gao XB, Sabrina Diano. Role of arcuate glial-neuronal interplay in feeding regulation. Cell Metabolism 2007 (1) 21-33
Abizaid A, Zhong-Wu, Andrews ZB, Elsworth JD, Roth RH, Sleeman M, Mineur YS, Gao XB, Picciotto MR, Tschöp M, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal of Clinical Investigation, 2006 116(12):3229-3239.
Andrews ZB, Rivera A, Elsworth JD, Roth RH, Agnati L, Gago B, Abizaid A, Schwartz M, Fuxe K, Horvath TL. Uncoupling protein 2 promotes nigrostriatal dopamine neuronal function. European Journal of Neuroscience, 2006 24:32-36.
Andrews ZB, Zhoa H, Frugier T, Meguro R, Grattan DR, Koishi K, McLennan IS. Transforming growth factor beta 2 haploinsufficient mice develop age-related nigrostriatal dopamine deficits. Neurobiology of Disease, 2006 21 (3): 568-575.
Andrews ZB, Diano S, Horvath TL. Mitochondrial uncoupling proteins in the CNS: In support of function and survival. Nature Reviews Neuroscience, 2005 6(11):829-40.
McGeachie AB, Koishi K, Andrews ZB, McLennan IS. Analysis of mRNAs that are enriched in the post-synaptic domain of the neuromuscular junction. Molecular and Cellular Neuroscience 2005 30(2):173-85
Andrews ZB. Neuroendocrine regulation of prolactin secretion during late pregnancy: easing the transition into lactation. Journal of Neuroendocrinology. 2005 17(7):466-73.
Conti B, Sugama S, Lucero J, Winsky-Sommerer R, Wirz SA, Maher P, Andrews Z, Barr AM, Morale MC, Paneda C, Pemberton J, Gaidarova S, Behrens MM, Beal F, Sanna PP, Horvath T, Bartfai T. Uncoupling protein 2 protects dopaminergic neurons from acute 1,2,3,6-methyl-phenyl-tetrahydropyridine toxicity. Journal of Neurochemistry 2005 93(2):493-501.
Andrews ZB, Horvath B, Barnstable CJ, Elsworth J, Yang L, Beal MF, Roth RH, Matthews RT, Horvath TL. Uncoupling protein-2 is critical for nigral dopamine cell survival in a mouse model of Parkinson's disease. Journal of Neuroscience. 2005 25(1):184-91.
