Brigitte Kieffer PhD
- Division:Basic Neuroscience
Associated Researcher, Douglas Research Centre
The Kieffer laboratory is interested in G protein coupled receptors in mental health and disease. G protein coupled receptors (GPCRs) are major targets in biomedicine and show huge potential for psychiatric disorders. Our goal is to elucidate where and how GPCRs control neuronal signaling and functional connectivity in the living brain to regulate normal and pathological behavior. Towards this goal, we develop and study customized mice with targeted GPCR gene mutations (conditional knockout, knock-in). We develop pioneering approaches towards (i) unbiased behavioral phenotyping to challenge both neural processes and symptomatology, (ii) hyperresolutive non-invasive brain imaging in living animals that combines structural and functional Magnetic Resonance Imaging and (iii) cutting-edge molecular imaging of GPCR signaling in vivo using multiphoton microscopy to connect neuronal signaling with network activities. Emphasis is (i) on opioid receptors, to study reward processing and implication in addiction, depression and autism syndrome disorders, and (ii) selected orphan GPCRs (oGPCRs), whose functions in the brain remain unknown, for discovery programs.
B. L. Kieffer is Professor at the Dpt Psychiatry, McGill University and the Scientific Director of the Douglas Mental Health Research Center in Montréal since 2014. She also is Professor at the Université de Strasbourg France, where she developed most her past research activity (IGBMC, one of the leading European centres of biomedical research). She has isolated the first gene encoding an opioid receptor, opening an entire research field towards understanding the molecular basis of opioid-controlled behaviors. Her genetic dissection of the opioid system has brought major advances in pain, addiction and mood disorders research, as well as in the area of molecular pharmacology and G protein coupled receptor research. She has developed and shared exquisite genetic tools worldwide, and has developed innovative research lines with strong impact in neuroscience and biomedical research. She has received numerous awards, including the Lounsbery (French and US Academies of Science) and the Lamonica Award of Neurology (French Academy of Science). In march 2014, she also received the International L’OREAL-UNESCO Award for Women in Science (European Laureate). She became an EMBO (European Molecular Biology Organization) member in 2009 and was elected as a member of the French Academy of Sciences in 2013.
Recent news
Recent publications
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Mu opioid receptors on hippocampal GABAergic interneurons are critical for the antidepressant effects of tianeptine. Neuropsychopharmacology. 2021.
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Ackr3-Venus knock-in mouse lights up brain vasculature. Mol Brain. 2021;14(1):151.
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Mapping the living mouse brain neural architecture: strain-specific patterns of brain structural and functional connectivity. Brain Struct Funct. 2021;226(3):647-669.
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Increased functional coupling of the mu opioid receptor in the anterior insula of depressed individuals. Neuropsychopharmacology. 2021;46(5):920-927.
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Chronic generalized pain disrupts whole brain functional connectivity in mice. Brain Imaging Behav. 2021;15(5):2406-2416.
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Design, Synthesis, and Structure-Activity Relationship Studies of (4-Alkoxyphenyl)glycinamides and Bioisosteric 1,3,4-Oxadiazoles as GPR88 Agonists. J Med Chem. 2020;63(23):14989-15012.
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NOP receptor agonist attenuates nitroglycerin-induced migraine-like symptoms in mice. Neuropharmacology. 2020;170:108029.
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Oxycodone-Mediated Activation of the Mu Opioid Receptor Reduces Whole Brain Functional Connectivity in Mice. ACS Pharmacol Transl Sci. 2019;2(4):264-274.
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Synaptic zinc contributes to motor and cognitive deficits in 6-hydroxydopamine mouse models of Parkinson's disease. Neurobiol Dis. 2019;134:104681.
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An Anti-Opioid System, Courtesy of a Worm Model. N Engl J Med. 2019;381(21):2067-2069.
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Biased Signaling of the Mu Opioid Receptor Revealed in Native Neurons. iScience. 2019;14:47-57.
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Deformation-based Morphometry MRI Reveals Brain Structural Modifications in Living Mu Opioid Receptor Knockout Mice. Front Psychiatry. 2018;9:643.
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Discovery of a Potent, Selective, and Brain-Penetrant Small Molecule that Activates the Orphan Receptor GPR88 and Reduces Alcohol Intake. J Med Chem. 2018;61(15):6748-6758.
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Opioid receptors: drivers to addiction? Nat Rev Neurosci. 2018;19(8):499-514.
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The Control of Reward Seeking. Biol Psychiatry. 2018;83(12):981-983.
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