Dr William F. Colmers
Professor & AHFMR Medical Scientist
BA Earth & Planetary Sciences, Johns Hopkins University, 1974
MA Earth & Planetary Sciences and Biophysics, Johns Hopkins University, 1974
Dr rer nat Zoology, University of Regensburg, Germany, 1980
Teaching: PMCOL371*, PMCOL343, PMCOL412
Research: Actions of neuropeptides in the brain-energy balance, anxiety
Research Interests / Laboratory Techniques
My laboratory studies the biological role which Neuropeptide Y (NPY), and related signals play in different brain regions. We are funded by the Canadian Institutes of Health Research (CIHR) and the US National Institutes of Health (NIH).
Energy Balance: Body weight and composition is controlled by a complex network of neurons in the brain, a large proportion of which are in the hypothalamus, ans which regulate the intake and expenditure of energy. Disorders of energy balance such as obesity and cachexia are widespread health problems. NPY injection into several regions of the hypothalamus causes a remarkable increase in food intake, even in fully-satiated animals. Continued treatment with NPY can result in obese animals.
Obesity: We are examining the brain mechanisms by which NPY causes this increase, studying neurons in the paraventricular (PVN) and ventromedial (VMN) nuclei of the hypothalamus. NPY affects transmitter release onto some neurons, and inhibits neurons in other areas, especially ones that are sensitive to the fat hormone, leptin. Other chemical messengers that regulate energy balance also have actions on NPY-sensitive systems. We are now feeding rats a high-fat diet, switching them back to low fat food and examining the brain responses of those that stay fat and those that return to their normal weight.
Cachexia: Patients with chronic diseases such as cancers or heart disease often lose large amounts of weight, further endangering their health and recovery. We are studying the brain in model systems to determine if the changes that happen in obesity are pushed in the opposite direction in cachexia
Anxiety: NPY acts at two receptor populations, Y1 and Y2, that have opposite actions on animals' reactions to stress. Y1 receptors relax an animal and Y2 receptors make them anxious. We are studying the mechanisms by which this occurs.
Selected Recent Publications
Bischof JM, Van Der Ploeg LH, Colmers WF and Wevrick R. (2016) Magel2-null mice are hyper-responsive to setmelanotide, a melanocortin 4 receptor agonist. Br J Pharmacol 173(17):2614-21. PMID: 27339818.
Zangrandi L, Burtscher J, MacKay JP, Colmers WF and Schwarzer C. (2016) The G-protein biased partial kappa opioid receptor agonist 6' GNTI blocks hippocampal paroxysmal discharges without inducing aversion. Br J Pharmacol 173(11):1756-67. PMID: 26928671.
Luchtman DW, Chee MJ, Doslikova B, Marks DL, Baracos VE and Colmers WF. (2015) Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular Hypothalamic Nucleus. PLoS One 10(10):e0139462. PMID: 26444289.
Pravdivyi I, Ballanyi K, Colmers WF and Wevrick R. (2015) Progressive postnatal decline in leptin sensitivity of arcuate hypothalamic neurons in the Magel2-null mouse model of Prader-Willi syndrome. Hum Mol Genet 24(15):4276-83. PMID: 25926624.
Colmers WF. (2013) If there is a weight set point, how is it set? Can J Diabetes 37 Suppl 2:S250. PMID: 24071202.
Hamilton TJ, Xapelli S, Michaelson SD, Larkum ME, Colmers WF. (2013) Modulation of distal calcium electrogenesis by neuropeptide y1 receptors inhibits neocortical long-term depression. J Neurosci 33(27):11184-93. PMID: 23825421.
Mercer RE, Michaelson SD, Chee MJ, Atallah TA, Wevrick R, Colmers WF (2013) Magel2 is required for leptin-mediated depolarization of POMC neurons in the hypothalamic arcuate nucleus in mice. PLoS Genet 9(1):e1003207. PMID: 23341784.
Lu VB, Colmers WF and Smith PA. (2012) Long-term actions of BDNF on inhibitory synaptic transmission in identified neurons of the rat substantia gelatinosa. J Neurophysiol 108:441-452. PMID: 22496528.
Chee MJ, Price CJ, Statnick MA and Colmers WF. (2011) Nociceptin/orphanin FQ suppresses the excitability of neurons in the ventromedial nucleus of the hypothalamus. J Physiol 589(Pt 13):3103-3114. PMID: 21502286.
Mercer RE, Chee MJ, Colmers WF. (2011) The role of NPY in hypothalamic mediated food intake. Front Neuroendocrinol. 32(4):398-415. PMID: 21726573.
Giesbrecht CJ, Mackay JP, Silveira HB, Urban JH, Colmers WF. (2010) Countervailing modulation of Ih by NPY and CRF in Basolateral Amygdala as a possible mechanism for their effects on stress-related behaviors. J. Neuroscience 30 :16970-16982. PMID: 21159967.
Hamilton TJ, Wheatley BM, Sinclair DB, Bachmann M, Larkum ME, Colmers WF. (2010) Opposing actions of Neuropeptide Y and Dopamine on dendritic Ca2+ electrogenesis in dentate granule cells. Proc Natl Acad Sci USA 107:18185-18190. PMID: 20921404.
Chee MJS, Myers Jr MG, Price CJ, Colmers WF. (2010) Neuropeptide Y Suppresses Anorexigenic Output from the Ventromedial Nucleus of the Hypothalamus. J. Neuroscience 30:3380-3390. PMID: 20203197.
Silveira Villarroel H, Bompolaki M, Mackay JP, Miranda Tapia AP, Michaelson SD, Leitermann RJ, Marr RA, Urban JH, Colmers WF. NPY induces stress resilience via downregulation of Ih in principal neurons of rat basolateral amygdala. J Neurosci. 38:4505-4520. (2018)