Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Caroline Marie Voss PhD fellow Molecular and Cellular Pharmacology Postal address: Jagtvej 160 2100 København Ø Email: [email protected] Phone: +45 35 33 36 11 Short presentation My project is concerned with brain energy metabolism in astrocytes when AMP-activated protein kinase (AMPK) is activated. AMPK has been described as the master metabolic switch in various cell types [1]. In peripheral cells the sensor is activated during hypoxia and lack of energy substrates, switching on catabolic processes producing ATP and switching off anabolic processes consuming ATP [2,3]. The significance of AMPK in the periphery is widely acknowledged, but the role of this sensor in brain energy metabolism has been investigated mostly in neurons. Astrocytes play an important role in sustaining brain glutamate homeostasis and energy metabolism [4] and how AMPK regulates this in healthy astrocytes is largely unknown [5]. Type 2 diabetes mellitus (T2DM) has reached the level of a pandemic. Lately, convincing data has revealed that cognitive deficits are a common complication among T2DM patients [6, 7]. T2DM patients have a 1.5-2.5 times increased risk of dementia and one in 10-15 cases of dementia can be attributed to T2DM [8]. Furthermore, an Alzheimer’s disease (AD) like pattern of glucose hypometabolism is seen already in a pre-diabetic state [7]. Reduced AMPK activation may cause a decrease in catabolic processes, i.e. by glucose hypometabolism, thus, it is pertinent to investigate if dysfunctional AMPK signaling is involved in the observed cerebral glucose hypometabolism. References 1. Winder, W.W. and D.G. Hardie, AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol, 1999. 277(1 Pt 1): p. E1-10. 2. Hardie, D.G., AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev, 2011. 25(18): p. 1895-908. 3. Canto, C., et al., AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature, 2009. 458(7241): p. 1056-60. 4. McKenna, M.C., Glutamate pays its own way in astrocytes. Front Endocrinol (Lausanne), 2013. 4: p. 191. 5. Voss, C.M., et al., AMPK Activation Affects Glutamate Metabolism in Astrocytes. Neurochem Res, 2015. 6. Strachan, M.W., et al., Cognitive function, dementia and type 2 diabetes mellitus in the elderly. Nat Rev Endocrinol, 2011. 7(2): p. 108-14. 7. Baker, L.D., et al., Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol, 2011. 68(1): p. 51-7. 8. Exalto, L.G., et al., An update on type 2 diabetes, vascular dementia and Alzheimer's disease. Exp Gerontol, 2012. 47 (11): p. 858-64. PUBLICATIONS AMPK Activation Affects Glutamate Metabolism in Astrocytes Voss, C. M., Pajęcka, K., Stridh, M. H., Nissen, J. D., Schousboe, A. & Waagepetersen, H. S. 7 Apr 2015 In : Neurochemical research. 40, 12, p. 2431-2442 10 p. EDUCATION 2004-2007 High School, Frederiksborg Gymnasium 2008-2011 B.Sc. Pharm, University of Copenhagen, grade average: 9.3 2011-2015M.Sc. Pharm, University of Copenhagen, grade average: 11.1 EMPLOYMENT 2009-2012: Student employee, Licensing Division, The Danish Medicines Agency 2012: Enviso Group A/S, Glostrup 2014: Scholarship student in the research group of Helle Waagepetersen, Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, Health and Medical Sciences, University of Copenhagen RESEARCH EXPERIENCE AND SKILLS The experimental work for my master thesis was conducted in the research group of Helle Waaepetersen, Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, Health and Medicinal Sciences, University of Copenhagen with Helle Waagepetersen as my primary supervisor. The aim of the project was to elucidate the metabolic effects of activating the mammalian AMP-activated protein kinase (AMPK) in astrocytes. During my work I got experience with the following: -Incubation studies with 13C labeled isotopes -Tritium labeled uptake studies -Cell culturing -Mass spectrometric analyses followed by metabolic mapping -High-performance liquid chromatography -Enzymatic assays: glycogen, lactate, citrate -Protein determination assays -Data analyses and statistics Furthermore, I worked 8 months as a scholarship student (Febuary 2014-October 2014) in the research group of Helle Waagepetersen prior to my master thesis. In addition to working with the AMPK-project, I was local co-organizer of The 11th International Conference on Brain Energy Metabolism, May 2014 (ICBEM 2014) in Helsinge. As a student employee at the Danish Medicines Agency I worked with the processes of drug approval and I got in-depth understanding of laws and regulations within this area. During my work in Enviso Group I was responsible for writing grant applications for new projects in the company, which is invaluable in the field of research. Within my master’s studies I spent 6 months in an internship at Næstved Løve Apotek where I got hands on experience with the customers consuming drugs as well as teaching the pharmacy staff. As stated above, during my stay in the research group of Helle Waagepetersen, I have acquired extensive experimental experience and learned how to work structured, to produce data of high quality and to address challenges in an academic way. These jobs and tasks have, taken together, given me a broad understanding of the health and medical area and I believe that I am able to use the obtained competencies in my future scientific career. Moreover, working with the organization of ICBEM 2014 as well as attending, gave me experience in structuring a scientific meeting and networking with highly skilled international scientists in the field. LICENSE GRANTING COURSES Certified training in laboratory animal handling on FELASA level C, University of Copenhagen IT SKILLS MS Office LaTex GraphPad Prism Endnote