Domaine de recherche
Mon domaine de recherche s'appliquera à comprendre et investiguer les mécanismes génétiques, épigénétiques et moléculaires associés à dysfonction ventriculaire droite chez les patients attends d'hypertension artérielle pulmonaire. Ultimement, ma recherche vise au développement de nouveaux outils thérapeutiques et de nouveaux biomarqueurs de la dysfonction ventriculaire droite.
Description des travaux
L'hypertension artérielle pulmonaire (HTAP) est une maladie évolutive du système vasculaire pulmonaire entraînant une augmentation de la résistance vasculaire pulmonaire (RVP), une pression artérielle pulmonaire élevée, un dysfonctionnement ventriculaire droit (VD). Bien que le mécanisme physiopathologique de déclenchement d'origine de l'HTAP soit localisé dans la circulation pulmonaire, la gravité des symptômes et la survie sont fortement associées à la fonction du VD,. la dysfonction du VD reste la principale cause de décès de ces patients. Malgré l'importance clinique reconnue de la préservation de la fonction VD, les mécanismes moléculaires conduisant à la dysfonction VD restent mal étudiés et, par conséquent, il n'existe aucun traitement cliniquement établi pour la dysfonction du VD.
Mes travaux s'attachent à déchiffrer les mécanismes moléculaires impliqués dans la transition de l'hypertrophie adaptative à la dysfonction VD. L'objectif principal de mon programme de recherche est l'identification de nouvelles cibles thérapeutiques pour préserver la fonction VD.
Concrètement, en utilisant une approche complète, multidisciplinaire et translationnelle impliquant des cellules, des tissus humains, des modulateurs pharmacologiques bien établis, des modèles animaux de dysfonctionnement du VD indépendants de la circulation pulmonaire, des souris génétiquement modifiées, nous proposons de déterminer si la signalisation PARP-1/PKM2 représente un intégrateur moléculaire et une cible thérapeutique du stress oxydatif, du dysfonctionnement métabolique et de l'inflammation tissulaire dans les défaillances de VR. Plus précisément, mes travaux vont:
1) Déterminer si la sur-activation de PARP-1 et la localisation nucléaire PKM2 (dimères) sont des caractéristiques du VD décompensé.
2) Déterminer si la signalisation PARP-1/PKM2 relie la réponse des dommages à l'ADN à l'inflammation et aux dysfonctions métaboliques du VD.
3) En utilisant un modèle préclinique de dysfonction VD, vérifier si l'inhibition pharmacologique et génétique de PARP-1 ainsi que la tétramérisation forcée (rétention dans le cytosol) de PKM2 fournissent des effets cardio-protecteurs empêchant la décompensation VD.
Prix et distinctions
1- Bourses 1. The Cardio Vascular Network (CVN) scholarship, Hypertension Canada, 2019-2020 2. The Rupert Swift Scholarship. Recognition award for the excellence of early career in pulmonary hypertension, Pulmonary Vascular Research Institute, 2019-2020. 3. Paroian Familly PH Research scholarship, Pulmonary Hypertension Association of the Canada. 2018-2019. 4. Scholarship, FRQS, 2016-2017. 5. Scholarship program (1 year), CRIUCPQ. 2014-2015. 6. Scholarship program (1 year), CRIUCPQ. 2013-2014. Prix 1. Jane Morse Award for the Best Abstract, May 2019, ATS International Meeting, Dallas, Texas, USA. 2. Pulmonary Circulation Travel award, May 2019, ATS International Meeting, Dallas, Texas, USA. 3. Cournand and Comroe Young Investigator Award, finalist, November 2018 4. Abstract Scholarship, pulmonary Circulation, May 2018, ATS International Conference, San Diego, california, USA 5. 3cpr junior investigator travel stipend, American Heart Association, November 2016, New Orleans, Louisiana, USA 6. PhD oral presentation award, Scientific university research day CRIUCPQ, June 2016, Québec, QC, Canada. 7. Travel Award respiratory health network from FRQS for ATS, May 2016, San Fransisco, California, USA. 8. Abstract Scholarship, pulmonary Circulation, May 2015, ATS International Conference, Denver, Colorado, USA 9. Award for publication as first author, medical department, Univerté Laval, March 2015, Québec, Qc , Canada. 10. Cardiopulmonary Best Abstract Award, American Heart Association Scientific Sessions, November 2014, Chicago, Illinois, USA. 11. Excellence Award, Scientific university research day CRIUCPQ, June 2014, Québec, QC, Canada. 12. James C Hogg award of the Canadian thoracic society (CTS), American Thoracic Society, may 2014, San Diego, California, USA. 13. Travel Award respiratory health network from FRQS for ATS 2014, may 2014, San Diego, California, USA. 14. Grant Pierce Biomedical, cardiovascular forum, August 2013, Louisville, KY, USA (Declined). 15. First price, PhD oral presentation, Scientific university research day CRIUCPQ, May 2013, Québec, QC, Canada. 16. Young Investigator Award, Grover Conference, American Thoracic Society, September 2013, Sedalia, Colorado, USA. 17. Recognition Award, American Physiological Society, Cardiovascular Research section, Experimental Biology (EB) April 2013, Boston, MA, USA. 18. Merck Award, Scientific University research day of CRIUCPQ, June 2012,Québec, QC, Canada
Publications
34- Lampron MC, Vitry G, Nadeau V, Grobs Y, Paradis R, Samson N, Tremblay È, Boucherat O, Meloche J, Bonnet S, Provencher S, Potus F, Paulin R. PIM1 (Moloney Murine Leukemia Provirus Integration Site) Inhibition Decreases the Nonhomologous End-Joining DNA Damage Repair Signaling Pathway in Pulmonary Hypertension.. Arterioscler Thromb Vasc Biol 2020; 40(3):783-801.
- Vitry G, Paulin R, Grobs Y, Lampron MC, Shimauchi T, Lemay SE, Tremblay E, Habbout K, Awada C, Bourgeois A, Nadeau V, Paradis R, Breuils-Bonnet S, Roux-Dalvai F, Orcholski M, Potus F, Provencher S, Boucherat O, Bonnet S. Oxidized DNA Precursors Cleanup by NUDT1 Contributes to Vascular Remodeling in PAH.. Am J Respir Crit Care Med 2021; 203(5):614-627.
- Provencher S, Boucherat O, Potus F, Bonnet S. Pulmonary hypertension thresholds: time to lower further?. Lancet Respir Med 2020; 8(9):834-836.
- Omura J, Habbout K, Shimauchi T, Wu WH, Breuils-Bonnet S, Tremblay E, Martineau S, Nadeau V, Gagnon K, Mazoyer F, Perron J, Potus F, Lin JH, Zafar H, Kiely DG, Lawrie A, Archer SL, Paulin R, Provencher S, Boucherat O, Bonnet S. Identification of Long Noncoding RNA H19 as a New Biomarker and Therapeutic Target in Right Ventricular Failure in Pulmonary Arterial Hypertension.. Circulation 2020; 142(15):1464-1484.
- Provencher S, Potus F, Bonnet S. COVID-19 and the pulmonary vasculature.. Pulm Circ 2020; 10(3):2045894020933088.
- Potus F, Mai V, Lebret M, Malenfant S, Breton-Gagnon E, Lajoie AC, Boucherat O, Bonnet S, Provencher S. Novel insights on the pulmonary vascular consequences of COVID-19.. Am J Physiol Lung Cell Mol Physiol 2020; 319(2):L277-L288.
- Tian L, Wu D, Dasgupta A, Chen KH, Mewburn J, Potus F, Lima PDA, Hong Z, Zhao YY, Hindmarch CCT, Kutty S, Provencher S, Bonnet S, Sutendra G, Archer SL. Epigenetic Metabolic Reprogramming of Right Ventricular Fibroblasts in Pulmonary Arterial Hypertension: A Pyruvate Dehydrogenase Kinase-Dependent Shift in Mitochondrial Metabolism Promotes Right Ventricular Fibrosis.. Circ Res 2020; 126(12):1723-1745.
- Prisco SZ, Rose L, Potus F, Tian L, Wu D, Hartweck L, Al-Qazazi R, Neuber-Hess M, Eklund M, Hsu S, Thenappan T, Archer SL, Prins KW. Excess Protein O-GlcNAcylation Links Metabolic Derangements to Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.. Int J Mol Sci 2020; 21(19):7278.
- Potus F, Martin AY, Snetsinger B, Archer SL. Biventricular Assessment of Cardiac Function and Pressure-Volume Loops by Closed-Chest Catheterization in Mice.. J Vis Exp 2020; 0(0):Epub.
- Tian L, Xiong PY, Alizadeh E, Lima PDA, Potus F, Mewburn J, Martin A, Chen KH, Archer SL. Supra-coronary aortic banding improves right ventricular function in experimental pulmonary arterial hypertension in rats by increasing systolic right coronary artery perfusion.. Acta Physiol (Oxf) 2020; 229(4):e13483.
- Potus F, Pauciulo MW, Cook EK, Zhu N, Hsieh A, Welch CL, Shen Y, Tian L, Lima P, Mewburn J, D'Arsigny CL, Lutz KA, Coleman AW, Damico R, Snetsinger B, Martin AY, Hassoun PM, Nichols WC, Chung WK, Rauh MJ, Archer SL. Novel Mutations and Decreased Expression of the Epigenetic Regulator TET2 in Pulmonary Arterial Hypertension.. Circulation 2020; 141(24):1986-2000.
- Dasgupta A, Wu D, Tian L, Xiong PY, Dunham-Snary KJ, Chen KH, Alizadeh E, Motamed M, Potus F, Hindmarch CCT, Archer SL. Mitochondria in the Pulmonary Vasculature in Health and Disease: Oxygen-Sensing, Metabolism, and Dynamics.. Compr Physiol 2020; 10(2):713-765.
- Shimauchi T, Potus F, Bonnet S, Provencher S, Paulin R, Boucherat O.. Limitations and Flaws of Preclinical Pulmonary Hypertension Studies.. Adv Pulm Hypertens 2020; 19(2):47-54.
- Habbout K, Omura J, Awada C, Bourgeois A, Grobs Y, Krishna V, Breuils-Bonnet S, Tremblay E, Mkannez G, Martineau S, Nadeau V, Roux-Dalvai F, Orcholski M, Jeyaseelan J, Gutstein D, Potus F, Provencher S, Bonnet S, Paulin R, Boucherat O. Implication of EZH2 in the Pro-Proliferative and Apoptosis-Resistant Phenotype of Pulmonary Artery Smooth Muscle Cells in PAH: A Transcriptomic and Proteomic Approach.. Int J Mol Sci 2021; 22(6):2957.
- Malenfant S, Lebret M, Breton-Gagnon É, Potus F, Paulin R, Bonnet S, Provencher S. Exercise intolerance in pulmonary arterial hypertension: insight into central and peripheral pathophysiological mechanisms.. Eur Respir Rev 2021; 30(160):200284.
- Awada C, Grobs Y, Wu WH, Habbout K, Romanet C, Breuils-Bonnet S, Tremblay E, Martineau S, Paulin R, Bonnet S, Provencher S, Potus F, Boucherat O. (R)-Crizotinib Predisposes To and Exacerbates Pulmonary Arterial Hypertension in Animal Models.. Eur Respir J 2021; 57(5):2003271.
- Frump AL, Albrecht M, Yakubov B, Breuils-Bonnet S, Nadeau V, Tremblay E, Potus F, Omura J, Cook T, Fisher A, Rodriguez B, Brown RD, Stenmark KR, Rubinstein CD, Krentz K, Tabima DM, Li R, Sun X, Chesler NC, Provencher S, Bonnet S, Lahm T. 17?-Estradiol and estrogen receptor ? protect right ventricular function in pulmonary hypertension via BMPR2 and apelin.. J Clin Invest 2021; 131(6):e129433.
- Dasgupta A, Chen KH, Lima PDA, Mewburn J, Wu D, Al-Qazazi R, Jones O, Tian L, Potus F, Bonnet S, Archer SL. PINK1-induced phosphorylation of mitofusin 2 at serine 442 causes its proteasomal degradation and promotes cell proliferation in lung cancer and pulmonary arterial hypertension.. FASEB J 2021; 35(8):e21771.
- Potus F, Frump AL, Umar S, R Vanderpool R, Al Ghouleh I, Lai YC. Recent advancements in pulmonary arterial hypertension and right heart failure research: overview of selected abstracts from ATS2020 and emerging COVID-19 research.. Pulm Circ 2021; 11(3):20458940211037274.
- Mai V, Tan BK, Mainbourg S, Potus F, Cucherat M, Lega JC, Provencher S. Venous thromboembolism in COVID-19 compared to non-COVID-19 cohorts: A systematic review with meta-analysis.. Vascul Pharmacol 2021; 139(0):106882.
- Lajoie AC, Potus F. Sirtuin 3 and Uncouplin Protein 2, the Missing Link Between Genetics, Metabolism, and Pulmonary Arterial Hypertension.. J Am Heart Assoc 2021; 0(0):e023065.
- Lemay SE, Bonnet S, Potus F. Commentary on: Xbp1s-Ddit3, DNA damage and pulmonary hypertension.. Clin Sci (Lond) 2022; 136(1):163-166.
- Xiong PY, Motamed M, Chen KH, Dasgupta A, Potus F, Tian L, Martin A, Mewburn J, Jones O, Thébaud A, Archer SL. Inhibiting pyruvate kinase muscle isoform 2 regresses group 2 pulmonary hypertension induced by supra-coronary aortic banding.. Acta Physiol (Oxf) 2022; 0(0):e13764.
- Wu WH, Bonnet S, Shimauchi T, Toro V, Grobs Y, Romanet C, Bourgeois A, Vitry G, Omura J, Tremblay E, Nadeau V, Orcholski M, Breuils-Bonnet S, Martineau S, Ferraro P, Potus F, Paulin R, Provencher S, Boucherat O. Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension.. Thorax 2022; 77(3):247-258.
- Al-Qazazi R, Lima PDA, Prisco SZ, Potus F, Dasgupta A, Chen KH, Tian L, Bentley RET, Mewburn J, Martin AY, Wu D, Jones O, Maurice DH, Bonnet S, Provencher S, Prins KW, Archer SL. Macrophage-NLRP3 Activation Promotes Right Ventricle Failure in Pulmonary Arterial Hypertension.. Am J Respir Crit Care Med 2022; 206(5):608-624.
- Shimauchi T, Boucherat O, Yokokawa T, Grobs Y, Wu W, Orcholski M, Martineau S, Omura J, Tremblay E, Shimauchi K, Nadeau V, Breuils-Bonnet S, Paulin R, Potus F, Provencher S, Bonnet S. PARP1-PKM2 Axis Mediates Right Ventricular Failure Associated With Pulmonary Arterial Hypertension.. JACC Basic Transl Sci 2022; 7(4):384-403.
- Provencher S, Potus F, Blais-Lecours P, Bernard S, Martineau S, Breuils-Bonnet S, Weatherald J, Sweeney M, Kulikowski E, Boucherat O, Bonnet S. BET Protein Inhibition for Pulmonary Arterial Hypertension: A Pilot Clinical Trial.. Am J Respir Crit Care Med 2022; 205(11):1357-1360.
- Jutras-Beaudoin N, Toro V, Lajoie AC, Breuils-Bonnet S, Paulin R, Potus F. Neutrophil-Lymphocyte Ratio as an Independent Predictor of Survival in Pulmonary Arterial Hypertension: An Exploratory Study.. CJC Open 2022; 4(4):357-363.
- Hindmarch CCT, Tian L, Xiong PY, Potus F, Bentley RET, Al-Qazazi R, Prins KW, Archer SL. An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats.. Front Physiol 2022; 13(0):966454.
- Awada C, Bourgeois A, Lemay SE, Grobs Y, Yokokawa T, Breuils-Bonnet S, Martineau S, Krishna V, Potus F, Jeyaseelan J, Provencher S, Bonnet S, Boucherat O. G9a/GLP Targeting Ameliorates Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.. Am J Respir Cell Mol Biol 2023; 68(5):537-550.
- Yamamoto K, Lemay SE, Yokokawa T, Breuils-Bonnet S, Salem M, Potus F, Provencher S, Boucherat O, Bonnet S. DNA-Protein Kinase Catalytic Subunit as a Potential Target for Pulmonary Arterial Hypertension.. Am J Respir Cell Mol Biol 2023; 68(1):116-119.
- Boucherat O, Yokokawa T, Krishna V, Kalyana-Sundaram S, Martineau S, Breuils-Bonnet S, Azhar N, Bonilla F, Gutstein D, Potus F, Lawrie A, Jeyaseelan J, Provencher S, Bonnet S.. From heart to blood: LTBP-2 is a promising biomarker for pulmonary arterial hypertension.. Nat Cardiovasc Res 2022; 1(0):804-805.
- Potus F, Boucherat O.. From heart to blood: LTBP-2 is a promising biomarker for pulmonary arterial hypertension.. Nat Cardiovasc Res 2022; 1(0):804-805.
- Awada C, Boucherat O, Provencher S, Bonnet S, Potus F. The future of group 2 pulmonary hypertension: Exploring clinical trials and therapeutic targets.. Vascul Pharmacol 2023; 151(0):107180.
