DR PLOUFFE'S PATH TOWARD HER ACTUAL RESEARCH PROGRAMME

Dr Plouffe completed biochemistry undergraduate studies at Université de Sherbrooke (QC, Canada) (2000-2003). Then, she quickly developed a marked interest for G protein-coupled receptor (GPCR) signalling. As GPCRs represent the largest family of cell surface proteins, and control a vast repertoire of physiological functions, these receptors are the actual target of 30-50% of all prescribed drugs. She started her journey in this exciting research field by investigating the molecular mechanisms involved in the angiotensin type 2 receptor (AT₂R)-mediated neurite outgrowth as a MSc student (2003-2005). This work contributed to the understanding of the mechanisms underlying neuronal differentiation required for brain development. During her MSc studies, Dr Plouffe also contributed to the characterisation of new selective AT₂R agonists in collaboration with research teams from Uppsala University (Sweden). Then, Dr Plouffe completed a PhD in Neuroscience at University of Ottawa (ON, Canada) (2006-2011), where she identified the molecular mechanisms involved in the opposite regulation of dopamine D1 and D5 receptors by protein kinase C. Her work shed light on the mechanisms underlying the positive action of prefrontal cortex on motor activity and of the thalamic parafascicular nucleus on awareness. 

Dr Plouffe decided to pursue her research in the field of GPCR signalling by completing a postdoctoral training at the Institute for Research in Immunology and Cancer, part of University of Montreal (QC, Canada) (2012-2018) as part of Prof Michel Bouvier's research team, a world-wide recognised expert in the field of GPCR signalling. During her postdoctoral training, Dr Plouffe used Bioluminescence Resonance Energy Transfer (BRET)-based technology to tackle important questions related to GPCRs involved in metabolic disorders. In collaboration with Prof Ralf Jockers from Institut Cochin (France), she investigated the signalling parameters of the melatonin type 2 receptor preventing development of type 2 diabetes. She also worked on the ghrelin receptor, involved in energy homeostasis and food intake, in collaboration with Prof Birgitte Holst (University of Copenhagen). This study lead to the identification of the ghrelin receptor-induced biased signalling mediated by a new compound responsible for unique physiological outcomes observed in murine model. This was one of the rare studies translating biased signalling from a receptor to in vivo functions.

Dr Plouffe had also the opportunity to participate to a jointed collaboration with Prof Robert J. Lefkowitz, a Nobel Laureate from Duke University (USA), and Prof Georgios Skiniotis, an expert in electron cryomicroscopy (cryoEM) from Stanford University (USA) on a project that was particularly inspiring and determinant for her actual research programme. Classically, G protein activation by GPCRs occurs at the plasma membrane and is rapidly terminated by the recruitment of a protein called β-arrestin to the activated GPCRs. This promotes G protein uncoupling from receptor, GPCR internalisation and signalling arrest. However, during the past decade, emerging evidence suggest that many GPCRs can continue to activate G proteins from internal compartments after they have been internalized. This fruitful collaboration allowed to appreciate the important role of β-arrestin in this novel type of G protein signalling and provided strong evidence for the formation of signalling complexes (called megaplexes) composed of the GPCR, G proteins and β-arrestin.

DR PLOUFFE'S RESEARCH PROGRAMME

The cellular responses promoted by GPCRs signalling from intracellular compartments are different than those of GPCRs signalling at the plasma membrane. The absence of desensitising effect of β-arrestin on GPCRs signalling from intracellular compartments is generally translated to a sustained and prolonged signalling as opposed to the transient kinetic observed for GPCRs signalling at the plasma membrane. Furthermore, G protein signalling from intracellular compartments allows a proximity with different effectors. As a Lecturer (confirmed in post; permanent position) and principal investigator at Queen’s University Belfast, Dr Plouffe aims to understand how subcellular location of GPCRs shapes cellular physiology and to use this knowledge to design new pharmacological approaches. Dr Plouffe's current targets are diabetic retinopathy and glioblastoma.

CURRENT PROJECTS IN THE LAB

1- To investigate the mechanisms translating Gq signalling from endosomes.

2- To delineate the role of secreted Frizzled related protein 2 in the pathogenesis of diabetic retinopathy. 

3- To investigate the role of US28 subcellular location in its oncomodulatory properties in the context of glioblastoma. 

4- To understand allosteric and biased GPCR signalling by the NTSR1, CCR4, and PAR2.   

PAST AND PRESENT GROUP MEMBERS

Postdoctoral Research Fellows:

- Dr Carole Daly (2022-Present)

Project: Investigation of the mechanisms underlying endosomal Gq signalling.

Technicians:

- Shane Houston (2019-2020)

PhD Students:

- Tianyi Ding (2019-Present; co-supervision)

Project: Understanding allosteric signaling of the C-C motif chemokine receptor 4.

- Akim Guseynov (2019-Present; co-supervision, CITI-GENS Marie Curie scholarship)

Project: Understanding allosteric and biased GPCR signaling from computer simulations and mutagenesis. Case Study: NTSR1

- Carole Daly 2019-2022 (DfE Scholarship)

Project: Investigation of the role of US28 subcellular location in the upregulation of oncomodulatory genes in the context of glioblastoma.

MSc Students:

- Adam Wright (2022-Present)

Project: Identification of the role of the formyl peptide receptor 2 in the pathogenesis of diabetic retinopathy.

- Stephen Copeland 2019-2020

Project: Non-canonical G protein signalling of US28 as a new target for glioblastoma.

Undergraduate Students:

- Padhraig McNicoll 2022-2023

- Adam McShane 2019-2020

Summer Students:

- Curtis Buchanan 2023 (BSc Biological Sciences, QUB, UK)

- Ashraf Mahmoud 2023 (Medical School, Kilimanjaro Christian Medical University College, Tanzania)

- Éloise Heulet 2019 (Advanced Biology, Université de Nantes, France)

- Lenka Toderova 2019 (Nuffield Research Placement)

- Cole Roberts 2019 (Medical School, University of Dundee, UK)

SELECTED AWARDS

• 2022 BBSRC New Investigator Award
• 2020 Diabetes UK Early-Career Small Grant for Basic Scientists
• 2018 Wellcome Trust Seed Award in Science
• 2017 Travel Award from the Institute for Research in Immunologie and Cancer
• 2016 Étudiant-Chercheurs Étoiles Award from Fonds de la Recherche du Québec en Santé
• 2016 Diabetes Canada Postdoctoral Award
• 2012 Canadian Institutes for Health Research Postdoctoral Award
• 2010 Best poster Award at the 2nd Brain Health and Research Day (Ottawa, Canada)
• 2010 University of Ottawa Tuition Fee Schorlarship
• 2009 Best poster Award at the 1^st Brain Health and Research Day (Ottawa, Canada)
• 2008 Travel Award from the American Society for Biochemistry & Molecular Biology
• 2007 Fonds de la Recherche du Québec en Santé Doctoral Award
• 2007 University of Ottawa Excellence Scholarship
• 2005 Best Poster Award from the Société de Neuroendocrinologie (France)
• 2004 Best Oral Presentation Award from Équipe de Physiopathologie Endocrinienne (Qc, Canada)

INVITED SPEAKER

• 2023 Invited Speaker - Imperial Membrane Receptor Network Seminar Series, Imperial College London (June 6th, London - UK).
• 2023 Invited Speaker - Seminar series, School of Molecular Biosciences, University of Glasgow (March 8th, Glasgow - UK).
• 2022 Invited Speaker - iGPCRnet 2nd Annual Meeting (Sept 30^th, Wurzburg - Germany).
• 2022 Invited Speaker - 6th European Research Network on Signal Transduction (online) (March 28-31).
• 2021 Invited Speaker - Seminar Series, Department of Molecular Pathobiology, NYU College of Dentistry (May 26^th, New York, USA).
• 2020 Invited Speaker - Seminar Series, Department of Pharmacy, Pharmaceutical Sciences and Biology, Baha'I Institute for Higher Education (November 19^th, Teheran - Iran).
• 2019 Invited Short Talk - Trafficking in Cancer Biology: Interplay, Targeting and Therapy (October 21-24, Turin - Italy).
• 2018 Invited speaker - Seminar Series, Department of Pharmaceutical Chemistry, Philipps-Universität Marburg (June 12^th, Marburg - Germany).
• 2018 Invited speaker - Seminar Series, Medical School, University of Nottingham (June 4^th, Nottingham - UK).
• 2018 Invited speaker - Seminar Series, Department of Medicinal Chemistry, Virginia Commonwealth University (May 24^th, Richmond - USA).
• 2017 Speaker - Seminar Series, Institute for Research in Immunology and Cancer, University of Montreal (September 22^nd, Montreal - Canada).
• 2017 Speaker - 7th Scientific Day, Institute for Research in Immunology and Cancer, University of Montreal (May 26^th, Montreal - Canada).
• 2017 Selected Short Talk - Molecular Pharmacology Gordon Research Seminars (March 12^th, Barga - Italy).
• 2015 Speaker - Seminar Series, Institute for Research in Immunology and Cancer, University of Montreal (April 24^th, Montreal - Canada).
• 2015 Speaker - MELA-BETES Joint Translational Call Meeting (March 20^th, Paris - France).
• 2014 Speaker - MELA-BETES Joint Translational Call Meeting (June 23^rd, Munich - Germany).
• 2013 Speaker - MELA-BETES Joint Translational Call Meeting (October 3^rd, Montreal - Canada).
• 2012 Speaker - MELA-BETES Joint Translational Call Meeting (December 21^st, Dresden - Germany).
• 2005 Selected Short Talk - 7^eJournée Scientifique de l’Équipe de Physiopathologie Endocrinienne (May, Lac Brome - Canada).
• 2004 Selected Short Talk - 6^eJournée Scientifique de l’Équipe de Physiopathologie Endocrinienne (September, Lac Brome - Canada).