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ZFIN ID: ZDB-PERS-170504-1
Kettunen, Petronella
Email: petronella.kettunen@neuro.gu.se
URL: http://kettunen.se
Affiliation: Kettunen Lab
Address: Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg Sweden
Country: Sweden
Phone:
Fax:
ORCID ID: 0000-0002-2510-3423


BIOGRAPHY AND RESEARCH INTERESTS
Petronella Kettunen is an associate professor at the Sahlgrenska Academy at University of Gothenburg and co-director of the Centre for Cognitive Medicine in Gothenburg, Sweden.

EDUCATION
MSc in Biomedicine, Karolinska Institutet, May 1999

PhD in Medicine (Neuroscience), Karolinska Institutet, November 2004.
Thesis title: Neuromodulation within a spinal locomotor network - role of metabotropic glutamate receptor subtypes. Supervisors: Abdel El Manira and Sten Grillner.

PREVIOUS POSITIONS

2015 – 2019: Visiting senior research fellow, University of Oxford, UK. Funded by MoRE (Mobility for Regional Excellence) grant from Region Västra Götaland.

2016 – 2018: Guest researcher, Neuro-Bio Ltd, Oxford, UK. Funded by a VINNMER grant, Vinnova.

2009 – 2013: Research fellow. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg. Funded by the Swedish Brain Foundation and Marie Skłodowska-Curie Actions.

2006 – 2009: Postdoctoral fellow. Departments of Physiological Science and Neurobiology, University of California Los Angeles, USA. Funded by the Hellmuth Hertz Foundation, Wenner-Gren Foundations and Swedish Society for Medical Research. 

2005: Grass Fellow. Marine Biological Laboratory, Woods Hole, MA, USA. Funded by the Grass Foundation.

2004 – 200: Research fellow. Department of Neuroscience, Karolinska Institutet.

1999 – 2004: PhD student. Department of Neuroscience, Karolinska Institutet. Funded by graduate student stipends from the Foundation for Strategic Research and KI Research Foundations.

RESEARCH PROJECTS

1. Molecular and cellular mechanisms of learning and memory
We are studying the molecular and cellular events that underlie learning. To this end, we are using the zebrafish (Danio rerio) and combining transgenic and molecular methods, behavioral experiments with imaging of structures in the nervous system.

The subproject FISHDOPA was financed 2016 – 2018 by FP7/EU via a Marie Skłodowska-Curie grant. It is focusing on understanding the role of the dopaminergic system in reward learning in fish https://cordis.europa.eu/project/id/660477). Read more about FISHDOPA.

We are also interested in human memory, memory testing and are associated with the Memory clinic in Mölndal, Sweden. Here, we are responsible for future genetic analysis of the patient material. In addition, Dr Kettunen is the co-director of the Center for Cognitive Medicine in Gothenburg, and organizes an annual PhD course in Learning and memory at University of Gothenburg.

2. Pathways underlying memory impairments and neurodegeneration in Alzheimer’s disease
We are interested in understanding how the Alzheimer’s disease-related peptide, amyloid-beta, is preventing memory formation in vivo. We are also studying the processes of amyloid-beta-mediated neurodegeneration in larval zebrafish and how these can be targeted for drug discovery. This project has received support from Sweden’s innovation agency Vinnova.

In parallel with the studies in the zebrafish we also study how cognitive decline is developed in patients. The Gothenburg MCI (Mild Cognitive Impairment) study was started in 1999 and has included close to 1000 healthy persons and patients with memory problems and followed them over time. We are making use of genetics, biomarkers, brain imaging and psychological test data to understand how the clinical decline is developing.

3. The role of microglia in Alzheimer’s disease
In our imaging experiments we are able to follow the dynamics of microglia, i.e. the immune cells of the brain, and combine these experiments with genetic analyses in human patient material. In this way, we hope to increase our understanding of the process of amyloid-beta clearance and the role of inflammation in Alzheimer’s disease. This project has received support by MORE (Mobility for Regional Excellence), Region Västra Götaland. Read more here: http://www.akademiliv.se/en/2013/03/10602/

The subproject INFLAMM-ALZ was financed between 2016 and 2018 by Horizon2020/EU to increase the understanding of how microglia cells are interacting with amyloid-beta (https://cordis.europa.eu/project/id/750403).

4. Evaluation of welfare parameters for zebrafish and establishment of guidelines for zebrafish housing
In this project with support from Formas (2019 – 2022), the government research council for sustainable development, we will raise and keep zebrafish under different conditions and measure different welfare markers. In this way, we can learn which conditions affect welfare in zebrafish. Our goal is establish guidelines for zebrafish housing which today is lacking.

5. Translational studies of the gene quaking
In collaboration with Lina Emilsson and Elena Jazin at Uppsala University we are investigating how the gene quaking contributes to the development of schizophrenia and other psychiatric disease. We are combining experiments in zebrafish with analyses in human material.

6. Neuronal networks underlying social behavior
In collaboration with the Westberg lab at Sahlgrenska Academy, we are investigating the molecular pathways and transmitter systems underlying social behavior and autism. This project is supported by the Swedish Research Council, clinical ALF project funding and the Swedish Brain Foundation (Hjärnfonden).

7. Treatment strategies for brain tumors
In collaboration with the Carén lab at Sahlgrenska Cancer Center, we use the zebrafish to investigate new treatments for brain tumors.


PUBLICATIONS
Landin, J., Hovey, D., Xu, B., Lagman, D., Zettergren, A., Larhammar, D., Kettunen, P., Westberg, L. (2020) Oxytocin Receptors Regulate Social Preference in Zebrafish. Scientific Reports. 10:5435
Kettunen, P. (2020) Calcium Imaging in the Zebrafish. Advances in experimental medicine and biology. 1131:901-942
Wenger, A., Larsson, S., Danielsson, A., Elbæk, K.J., Kettunen, P., Tisell, M., Sabel, M., Lannering, B., Nordborg, C., Schepke, E., Carén, H. (2017) Stem cell cultures derived from pediatric brain tumors accurately model the originating tumors. Oncotarget. 8(12):18626-18639
Banote, R.K., Edling, M., Eliassen, F., Kettunen, P., Zetterberg, H., Abramsson, A. (2016) β-Amyloid precursor protein-b is essential for Mauthner cell development in the zebrafish in a Notch-dependent manner. Developmental Biology. 413(1):26-38
Radomska, K.J., Sager, J., Farnsworth, B., Tellgren-Roth, Å., Tuveri, G., Peuckert, C., Kettunen, P., Jazin, E., Emilsson, L.S. (2016) Characterization and Expression of the Zebrafish qki Paralogs. PLoS One. 11:e0146155
Bliman, D., Nilsson, J.R., Kettunen, P., Andréasson, J., Grøtli, M. (2015) A Caged Ret Kinase Inhibitor and its Effect on Motoneuron Development in Zebrafish Embryos. Scientific Reports. 5:13109
Abramsson, A., Kettunen, P., Banote, R.K., Lott, E., Li, M., Arner, A., and Zetterberg, H. (2013) The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation. Developmental Biology. 381(2):377-88
Kettunen, P. (2012) Calcium imaging in the zebrafish. Advances in experimental medicine and biology. 740
Issa, F.A., O'Brien, G., Kettunen, P., Sagasti, A., Glanzman, D.L., Papazian, D.M. (2011) Neural circuit activity in freely behaving zebrafish (Danio rerio). The Journal of experimental biology. 213(Pt 6):1028-1038
Abramsson, A., Westman-Brinkmalm, A., Pannee, J., Gustavsson, M., von Otter, M., Blennow, K., Brinkmalm, G., Kettunen, P., and Zetterberg, H. (2010) Proteomics Profiling of Single Organs from Individual Adult Zebrafish. Zebrafish. 7(2):161-168
Neveu, P., Sinha, D., Kettunen, P., Vriz, S., Julien, L., Bensimon, D. (2010) Single cell physiology. Proceedings of the Nobel Symposium on Single Molecule Spectroscopy in Chemistry, Physics and Biology. 96:305-316

NON-ZEBRAFISH PUBLICATIONS
Westwood S, Baird AL, Anand SN, Nevado-Holgado AJ, Kormilitzin A, Shi L, Hye A, Ashton NJ, Morgan AR, Bos I, Vos SJB, Baker S, Buckley NJ, Ten Kate M, Scheltens P, Teunissen CE, Vandenberghe R, Gabel S, Meersmans K, Engelborghs S, De Roeck EE, Sleegers K, Frisoni GB, Blin O, Richardson JC, Bordet R, Molinuevo JL, Rami L, Wallin A, Kettunen P, Tsolaki M, Verhey F, Lléo A, Sala I, Popp J, Peyratout G, Martinez-Lage P, Tainta M, Johannsen P, Freund-Levi Y, Frölich L, Dobricic V, Legido-Quigley C, Bertram L, Barkhof F, Zetterberg H, Morgan BP, Streffer J, Visser PJ, Lovestone S. (2020) Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer’s Disease Multimodal Biomarker Discovery Cohort. J Alzheimers Dis. 74(1):213-225.

Göthlin M, Eckerström M, Lindwall M, Rolstad S, Eckerström C, Jonsson M, Kettunen P, Svensson J, Wallin A. (2020) Latent Cognitive Profiles Differ Between Incipient Alzheimer’s Disease and Dementia with Subcortical Vascular Lesions in a Memory Clinic Population. J Alzheimers Dis. 73(3):955-966.

Eckerström C, Eckerström M, Göthlin M, Molinder A, Jonsson M, Kettunen P, Svensson J, Rolstad S, Wallin A. (2020) Characteristic Biomarker and Cognitive Profile in Incipient Mixed Dementia. J Alzheimers Dis. 73(2):597-607.

Stamate D, Kim M, Proitsi P, Westwood S, Baird A, Nevado-Holgado A, Hye A, Bos I, Vos SJB, Vandenberghe R, Teunissen CE, Kate MT, Scheltens P, Gabel S, Meersmans K, Blin O, Richardson J, De Roeck E, Engelborghs S, Sleegers K, Bordet R, Ramit L, Kettunen P, Tsolaki M, Verhey F, Alcolea D, Lléo A, Peyratout G, Tainta M, Johannsen P, Freund-Levi Y, Frölich L, Dobricic V, Frisoni GB, Molinuevo JL, Wallin A, Popp J, Martinez-Lage P, Bertram L, Blennow K, Zetterberg H, Streffer J, Visser PJ, Lovestone S, Legido-Quigley C. (2019) A metabolite-based machine learning approach to diagnose Alzheimer-type dementia in blood: Results from the European Medical Information Framework for Alzheimer disease biomarker discovery cohort. Alzheimers Dement (N Y). 5:933-938.

Shi L, Westwood S, Baird AL, Winchester L, Dobricic V, Kilpert F, Hong S, Franke A, Hye A, Ashton NJ, Morgan AR, Bos I, Vos SJB, Buckley NJ, Kate MT, Scheltens P, Vandenberghe R, Gabel S, Meersmans K, Engelborghs S, De Roeck EE, Sleegers K, Frisoni GB, Blin O, Richardson JC, Bordet R, Molinuevo JL, Rami L, Wallin A, Kettunen P, Tsolaki M, Verhey F, Lleó A, Alcolea D, Popp J, Peyratout G, Martinez-Lage P, Tainta M, Johannsen P, Teunissen CE, Freund-Levi Y, Frölich L, Legido-Quigley C, Barkhof F, Blennow K, Zetterberg H, Baker S, Morgan BP, Streffer J, Visser PJ, Bertram L, Lovestone S, Nevado-Holgado AJ. (2019) Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay. Alzheimers Dement. 15(11):1478-1488.

Kim M, Snowden S, Suvitaival T, Ali A, Merkler DJ, Ahmad T, Westwood S, Baird A, Proitsi P, Nevado-Holgado A, Hye A, Bos I, Vos S, Vandenberghe R, Teunissen C, Ten Kate M, Scheltens P, Gabel S, Meersmans K, Blin O, Richardson J, De Roeck E, Sleegers K, Bordet R, Rami L, Kettunen P, Tsolaki M, Verhey F, Sala I, Lléo A, Peyratout G, Tainta M, Johannsen P, Freund-Levi Y, Frölich L, Dobricic V, Engelborghs S, Frisoni GB, Molinuevo JL, Wallin A, Popp J, Martinez-Lage P, Bertram L, Barkhof F, Ashton N, Blennow K, Zetterberg H, Streffer J, Visser PJ, Lovestone S, Legido-Quigley C. (2019) Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer’s Disease biomarker discovery cohort. Alzheimers Dement. 15(6):817-827.

Morgan AR, Touchard S, Leckey C, O’Hagan C, Nevado-Holgado AJ; NIMA Consortium, Barkhof F, Bertram L, Blin O, Bos I, Dobricic V, Engelborghs S, Frisoni G, Frölich L, Gabel S, Johannsen P, Kettunen P, Kłoszewska I, Legido-Quigley C, Lleó A, Martinez-Lage P, Mecocci P, Meersmans K, Molinuevo JL, Peyratout G, Popp J, Richardson J, Sala I, Scheltens P, Streffer J, Soininen H, Tainta-Cuezva M, Teunissen C, Tsolaki M, Vandenberghe R, Visser PJ, Vos S, Wahlund LO, Wallin A, Westwood S, Zetterberg H, Lovestone S, Morgan BP; Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer’s Disease. (2019) Inflammatory biomarkers in Alzheimer’s disease plasma. Alzheimers Dement. 15(6):776-787.

Göthlin M, Eckerström M, Rolstad S, Kettunen P, Wallin A. (2018) Better prognostic accuracy in younger mild cognitive impairment patients with more years of education. Alzheimers Dement (Amst). 10:193.

Vos SJ, Jansen WJ, Vandenberghe R, Gabel S, Estanga A, Ecay M,Tomassen J, den Braber A, Lleó A, Sala I, Wallin A, Kettunen P, Molinuevo JL, Rami L, Chetelat G, de la Sayette V, Tsolaki M, Freund-Levi Y, Johannsen P, the Alzheimer’s Disease Neuroimaging Initiative, Novak G, Ramakers I, Verhey F, Visser PJ. (2018) Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data. Front. Aging Neurosci. 10:193.

Wallin A, Román GC, Esiri M, Kettunen P, Svensson J, Paraskevas GP, Kapaki E. (2018) Update on Vascular Cognitive Impairment Associated with Subcortical Small-Vessel Disease. J Alzheimers Dis. 62(3):1417-1441.

Wallin A, Kettunen P, Johansson PM, Jonsdottir I, Nilsson C, Nilsson M, Eckerström M, Nordlund A, Nyberg L, Sunnerhagen K, Svensson J, Terzis B; Wahlund, L-O, Kuhn G (2018) Cognitive medicine – a new approach in health care science. BMC Psychiatry 18(1):42.

Agholme L, Clarin M, Gkanatsiou E, Kettunen P, Chebli J, Brinkmalm G, Blennow K, Bergström P, Portelius E, Zetterberg H. (2017) Low-dose γ-secretase inhibition increases secretion of Aβ peptides and intracellular oligomeric Aβ. Mol Cell Neurosci. 85:211-219.

Farnsworth B, Radomska KJ, Zimmermann B, Kettunen P, Jazin E, Emilsson LS. (2017) QKI6B mRNA levels are upregulated in schizophrenia and predict GFAP expression. Brain Res. 1669:63-68.

Zettergren A, Karlsson SA, Studer E, Sarvimäki A, Kettunen P, Thorsell A, Sihlbom C, Westberg L. (2017) Proteomic analyses of limbic regions in neonatal male, female and androgen receptor knockout mice. BMC Neurosci. 18: 9. doi:10.1186/s12868-016-0332-1.

Andersson C-H, Hansson O, Minthon L, Andreasen N, Blennow K, Zetterberg H, Skoog I, Wallin A, Nilsson S, Kettunen P. (2016) A genetic variant of the sortilin 1 gene is associated with reduced risk of Alzheimer’s disease. Journal of Alzheimer’s Disease. 53(4):1353-63.

Farnsworth B, Peuckert C, Zimmermann B, Jazin E, Kettunen P, Emilsson LS (2016) Gene expression of quaking in sporadic Alzheimer’s disease patients is both upregulated and related to expression levels of genes involved in amyloid plaque and neurofibrillary tangle formation. Journal of Alzheimer’s Disease. 53(1):209-19.

Karlsson SA, Studer E, Kettunen P and Westberg L (2016) Neural androgen receptors modulate gene expression and social recognition but not social investigation. Frontiers in Behavioral Neuroscience 10:41.

Karlsson, S. A., Haziri, K., Hansson, E., Kettunen, P., Westberg L. (2015) Effects of sex and gonadectomy on social investigation and social recognition in mice. BMC Neurosci. 16(1):83

Kettunen P., Larsson S., Holmgren S., Olsson S., Minthon L., Zetterberg H., Blennow K., Nilsson S., Sjölander, A. (2015) Genetic Variants of GSK3B are Associated with Biomarkers for Alzheimer’s Disease and Cognitive Function. J Alzheimers Dis. 44(4):1313-22. (Corresponding author)

Landgren, S., von Otter, M., Nilsson S., Seibt Palmér, M., Lundvall, C., Lennart Minthon, L., Bogdanovic, N., Andreasen, N., Gustafson, D.R., Skoog, I., Wallin, A., Blennow, K., Zetterberg, H. and Kettunen P. (2012) A novel ARC gene polymorphism is associated with reduced risk of Alzheimer’s disease. Journal of Neural Transmission 119(7):833-42. (Corresponding author)

Nanou, E., Kyriakatos A., Kettunen, P., and El Manira, A. (2009) Separate signaling mechanisms underlie mGluR1 modulation of leak channels and NMDA receptors in the network underlying locomotion. Journal of Physiology 587:3001-8.

Kettunen, P., Kyriakatos, A., Hallén, K. and El Manira, A. (2005) Neuromodulation via conditional release of endocannabinoids in the spinal locomotor network. Neuron 45:95-104.

Hallén, K., Huss, M., Kettunen, P., El Manira, A., and Hellgren-Kotaleski, J. (2004) mGluR-mediated calcium oscillations in the lamprey: a computational model. Neurocomputing 58-60:431-435.

Kettunen, P., Krieger, P., Hess, D. and El Manira, A. (2003) mGluR1, but not mGluR5, mediates depolarization of spinal cord neurons by blocking a leak current. Journal of Neurophysiology 90:2341-2348.

Kettunen, P., Demas, J., Lohmann, C., Kasthuri, N., Gong, Y., Wong, R.O.L. and Gan, W-B. (2002) Calcium dynamics in the nervous system by means of ballistic delivery of indicators. Journal of Neuroscience Methods 119:37-43.

Kettunen, P., Krieger, P., Hess, D. and El Manira A. (2002) Signalling mechanisms of metabotropic glutamate receptor 5 subtype and its endogenous role in a locomotor network. Journal of Neuroscience 22:1868-1873.

El Manira A., Kettunen, P., Hess, D. and Krieger, P. (2002) Metabotropic glutamate receptors provide intrinsic modulation of the lamprey locomotor network. Brain Research Reviews 40:9-18.

Krieger, P., Hellgren-Kotaleski, J., Kettunen, P. and El Manira, A. (2000) Interaction between metabotropic and ionotropic glutamate receptors regulates neuronal network activity. Journal of Neuroscience 20:5382-53.