Team Leader
Team Leader
Research Director
Team Leaders : Hafid Ait-Oufella and Ziad Mallat
Mail : hafid.aitoufella@inserm.fr
Phone :+33 1 53 98 80 06
Localisation : 2nd floor
DOCTORAL SCHOOL : ED 562 – BIO SCIENCE PARIS CITE – Université PARIS CITE
Cardiovascular diseases will remain the main cause of death within the next fifteen years forcing us to revisit their basic mechanisms and consider new therapeutic strategies.
Our group is interested in the study and modulation of innate and adaptive immune responses during atherosclerosis development, post-ischemic cardiac remodeling and aortic aneurysm formation. Furthermore, we are interested in the interplay between cardiovascular diseases and their associated co-morbidities, and more particularly, the mechanisms involved in the development of obesity and metabolic syndrome in the context of high fat diet.
Trained immunity in cardiometabolic diseases
Hafid Ait-Oufella, Ziad Mallat & Soraya Taleb
Immune cells can retain the memory of an encounter with bacteria or oxidized lipids and this memory called “trained immunity” has a lasting effect on their functions. The objective of this new project is to better understand the phenomenon of trained immunity applied to experimental cardiometabolic diseases and to dissect its cellular and molecular mechanisms.
Targeting cytotoxic immune cells in post-ischemic cardiac remodeling
Hafid Ait-Oufella
We aim to investigate with unique genetically-modified mouse models the role of NK cells, which infiltrate the heart in the context of myocardial infarction and release large amounts of cytotoxic Perforin/Granzyme B.
Intestinal cell metabolism and the control of cardiovascular diseases
Soraya Taleb
The gut microbiota may modulate cardiometabolic diseases but the mechanisms that link both gut and vascular compartments remains poorly understood. We aim to study the role of indoleamine 2, 3-dioxygenase 1 activity as well as derived metabolites in intestinal cell metabolism, gut microbiota, and cardiovascular diseases.
Team Leader
Team Leader
Research Director
Scientist
Engineer
Engineer
Engineer
Engineer
Engineer
Postdoctoral Fellow
Postdoctoral Fellow
Postdoctoral fellow
Postdoctoral fellow
Postdoctoral fellow
PhD Student
PhD Student
PhD Student
PhD Student
PhD Student
PhD Student
Clinician
TEAM AWARDS
Soraya Taleb
2023 Outstanding Achievement Award – ESC
2023 Prix de Recherche FRM/Institut Danone
2021 Prix Lucie et Olga Fradiss (SFC)
2019-2023 PEDR Inserm
Sarvenaz Metghalchi
2017 Prix Poster (EAS)
Nada Joe Melhem
2021 Paul Dudley White International Scholar Award
2020 Prix de Thèse (GRRC)
2018 PrixPoster (Printemps de la Cardiologie)
2018 Prix Présentation Orale (EAS)
Mouna Chajadine
2022 Prix Poster (NSFA)
Nirmala Mouttoulingham
2023 Prix Présentation orale (NSFA)
Tobias Radecke
2021 Scholarship DFG Walter Benjamin Programme : https://gepris.dfg.de/gepris/projekt/490937447?language=en
TEAM FUNDINGS
During the 2017-2022 period, the team has obtained 20 grants, including:
– 7 projects (as Coordinator) funded by the French Research National Agency:
ANR: JCJC IDOAMI (2016-2020);
ANR-16-CE14-0016 EMOTION (2016-2019);
ANR-18-CE14-0009 – TETRAAA (2019-2022);
ANR-18-CE14-0009 TREKING (2021-2024);
ANR-20-COV1-0002 2020;
ANR-21-CE14-0007-01 IACOTA (2021-2023);
ANR-22CE14-0014-01, MIMEA (2022-2024).
– 1 project (as partner) funded by ANR:
ANR-17-CE14-0005-02 BRAINWASH, 2017-2020.
– 3 projects by Fondation de France
– 2 projects funded by Fédération Francaise de Cardiologie
– 2 “Equipe FRM” Label:
DEQ20160334913 2016-2019
EQU202103012589, 2021-2024
– 2 ERA NET CVD grants
– 1 Horizon H2020 grant (RITA-MI2, phase IIb trial)
– 1 Horizon Europe grant (TiilT, to start in 2023)
-Alternating high-fat diet enhances atherosclerosis by neutrophil reprogramming. Lavillegrand JR, Al-Rifai R, Thietart S, Guyon T, Vandestienne M, Cohen R, Duval V, Zhong X, Yen D, Ozturk M, Negishi Y, Konkel J, Pinteaux E, Lenoir O, Vilar J, Laurans L, Esposito B, Bredon M, Sokol H, Diedisheim M, Saliba AE, Zernecke A, Cochain C, Haub J, Tedgui A, Speck NA, Taleb S, Mhlanga MM, Schlitzer A, Riksen NP, Ait-Oufella H. Nature. 2024 Oct;634(8033):447-456. doi: 10.1038/s41586-024-07693-6. Epub 2024 Sep 4. PMID: 39232165 Free PMC article.
-Early intermittent hyperlipidaemia alters tissue macrophages to fuel atherosclerosis. Takaoka M, Zhao X, Lim HY, Magnussen CG, Ang O, Suffee N, Schrank PR, Ong WS, Tsiantoulas D, Sommer F, Mohanta SK, Harrison J, Meng Y, Laurans L, Wu F, Lu Y, Masters L, Newland SA, Denti L, Hong M, Chajadine M, Juonala M, Koskinen JS, Kähönen M, Pahkala K, Rovio SP, Mykkänen J, Thomson R, Kaisho T, Habenicht AJR, Clement M, Tedgui A, Ait-Oufella H, Zhao TX, Nus M, Ruhrberg C, Taleb S, Williams JW, Raitakari OT, Angeli V, Mallat Z. Nature. 2024 Oct;634(8033):457-465. doi: 10.1038/s41586-024-07993-x. Epub 2024 Sep 4. PMID: 39231480 Free PMC article.
-Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice. Chajadine M, Laurans L, Radecke T, Mouttoulingam N, Al-Rifai R, Bacquer E, Delaroque C, Rytter H, Bredon M, Knosp C, Vilar J, Fontaine C, Suffee N, Vandestienne M, Esposito B, Dairou J, Launay JM, Callebert J, Tedgui A, Ait-Oufella H, Sokol H, Chassaing B, Taleb S. Nat Commun. 2024 Jul 29;15(1):6390. doi: 10.1038/s41467-024-50807-x. PMID: 39080345 Free PMC article.
-L-Wnk1 Deletion in Smooth Muscle Cells Causes Aortitis and Inflammatory Shift. Quelquejay H, Al-Rifai R, Silvestro M, Vandestienne M, Ferreira I, Mirault T, Henrion D, Zhong X, Santos-Zas I, Goudot G, Alayrac P, Robidel E, Autret G, Balvay D, Taleb S, Tedgui A, Boulanger CM, Zernecke A, Saliba AE, Hadchouel J, Ramkhelawon B, Cochain C, Bergaya S, Jeunemaitre X, Ait-Oufella H. Circ Res. 2024 Aug 2;135(4):488-502. doi: 10.1161/CIRCRESAHA.124.324366. Epub 2024 Jul 9. PMID: 38979610 Free article.
– An obesogenic diet increases atherosclerosis through promoting microbiota dysbiosis-induced gut lymphocyte trafficking into the periphery. Laurans L, Mouttoulingam N, Chajadine M, Lavelle A, Diedisheim M, Bacquer E, Creusot L, Suffee N, Esposito B, Melhem NJ, Le Goff W, Haddad Y, Paul JL, Rainteau D, Tedgui A, Ait-Oufella H, Zitvogel L, Sokol H, and Taleb S. Cell Rep. 2023 October 31, Volume 42, Issue 11
– Genetic inhibition of CARD9 accelerates the development of atherosclerosis in mice through CD36 dependent-defective autophagy. Zhang Y, Vandestienne M, Lavillegrand JR, Joffre J, Santos-Zas I…. Silvestre JS, Tedgui A, Mallat Z, Taleb S, Lenoir O, Vindis C, Camus SM, Sokol H, Ait-Oufella H. Nat Commun. 2023 Aug 1;14(1):4622.
– JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm. Al-Rifai R, Vandestienne M, Lavillegrand JR, … Tedgui A, Lacroix M, Arrive L, Mallat Z, Taleb S, Diedisheim M, Cochain C, Rautou PE, Ait-Oufella H. Nat Commun. 2022Nov 3;13(1):6592.
– Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling. I Santos-Zas, J Lemarié, I Zlatanova, M …. A Tedgui, Z Mallat, T Simon, B Ghaleh, JS Silvestre & H Ait-Oufella.Nat Commun. 2021 Mar 5;12(1):1483.
– Endothelial Cell Indoleamine 2, 3-Dioxygenase 1 Alters Cardiac Function After Myocardial Infarction Through Kynurenine. Melhem NJ, ..Mallat Z, Tedgui A, Ait-Oufella H, Hulot JS, .., Silvestre JS, Taleb S. Circulation. 2021 Feb 9;143(6):566-580.
– TREM-1 orchestrates Angiotensin II-induced monocyte trafficking and promotes experimental abdominal aortic aneurysm. M Vandestienne, Y Zhang, I Santos-Zas, R Al-Rifai, J Joffre, ….Guerin, E Clauser, JS Silvestre, S Lang, L Soulat-Dufour, A Tedgui, Z Mallat, S Taleb, A Boissonnas, M Derive, G Chinetti & Ait-Oufella H. J Clin Invest. 2021 Jan 19;131(2)
– Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health. Laurans L, … Tavitian B, … Tedgui A, Mallat Z, … Taleb S. Nat Med. 2018 Aug;24(8):1113-1120.
– Selective EGF-Receptor Inhibition in CD4+ T Cells Induces Anergy and Limits Atherosclerosis. Zeboudj L, Maître M, Guyonnet L, ….Tedgui A, Mallat Z, Tharaux PL, Ait-Oufella H. J Am Coll Cardiol. 2018 Jan 16;71(2):160-172.
