The laboratory of Thrombosis and Hemostasis is located in the Research Center of the Montreal heart Institute. This laboratory is directed by Dr. Merhi, full professor in the Department of Medicine at the University of Montreal. He specializes in the study of blood reactions (platelets, endothelial progenitor cells, leukocytes, coagulation) in cardiovascular disease and coronary heart disease, in particular the acute coronary syndrome.
Our research program aims to study and to understand the mechanisms at work in the crosstalk between blood cells and platelets in thrombosis or blood clot formation and how these reactions are affected by inflammatory molecules.
Our experimental approaches include molecular and pharmacological tools with isolated blood cells, and clinically relevant animal models of heart vessel disease. We are also involved in translational research, aiming to assess the efficacy of new anti-platelet and anti-coagulant drugs in pre-clinical studies.
We intend to identify new drugs and to propose innovative approaches in the clinical management of thrombotic heart disease.
Yahye Merhi, Ph. D., Director, yahye.merhi@icm-mhi.org, 514-376-3330 # 3035
Souhad El Akoum, Ph.D., Postdoc fellow, elakoum_souhad@hotmail.com, 514-376-3330 #3155
Kevin Kojok, Ph.D. student, kevin.kojok@outlook.com
Rahma Boulahya, Ph.D. student in collaboration with Dr Marie Lordkipanidzé's lab, rahma.mrad@gmail.com
Mourad Dandachli, Master's degree student in collaboration with Dr. Walid Mouras' lab at the CRCHUM, mourad.dandachli@umontreal.ca
Heart disease can be caused by multiple risk factors, which cause inflammation by activating blood cells, and damage blood vessels. Unfortunately, current interventions and drug treatments do not prevent completely or limit the progression and the occurrence of narrowed and blocked heart blood vessels. Actually, a subset of progenitor cells called endothelial progenitor cells have shown promising results in repairing the damaged arteries and in limiting the reactions of platelets, the principal blood cells involved in blood clots. However, some inflammatory molecules in blood, such as CD40 ligand, may affect platelets and the function of endothelial progenitior cells and their capacity to reduce blood clot formation.
Our research program aims to study and to understand the mechanisms at work in the crosstalk between platelets and endothelial progenitor cells in thrombosis or blood clot formation and how these reactions are affected by the inflammatory molecule CD40 ligand. We will address the central hypothesis that CD40 ligand activates platelets and reduces the function of endothelial progenitor cells, which results in enhanced platelet reactivity and blood clot formation.
Our strategy includes in vitro study with isolated blood cells and in vivo study with clinically relevant animal models of heart vessel disease.
This research program is largely based on a new concept that CD40 ligand is a thrombo-inflammatory molecule that, with its receptor CD40 on platelets and endothelial progenitor cells, plays an important role in thrombosis. This concept is innovative in the field of vascular biology, thrombosis and hemostasis. Our laboratory was the first to highlight this concept, both at the cellular and pharmacological levels, in several publications We are addressing new important original questions and proposing established and innovative approaches to reveal new basic mechanisms in platelet function and endothelial progenitor cell biology, which are relevant for understanding the process of thrombosis and vessel narrowing. These insights should enable us to identify new drugs and to the discovery of innovative therapeutic options in the clinical management of coronary heart diseases.
For complete list of publications
Bou Khzam L, Bouchereau O, Boulahya R, Hachem A, Zaid Y, Abou-Saleh H, Merhi Y. Early outgrowth cells versus endothelial colony forming cells functions in platelet aggregation. J Transl Med. 2015 Nov 9;13:353. doi: 10.1186/s12967-015-0723-6.
Noel S, Hachem A, Merhi Y, De Crescenzo G. Development of a Polyester Coating Combining Antithrombogenic and Cell Adhesive Properties: Influence of Sequence and Surface Density of Adhesion Peptides. Biomacromolecules. 2015 Jun 8;16(6):1682-94. doi: 10.1021/acs.biomac.5b00219. Epub 2015 May 4.
Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent manner. Abou-Saleh H, Hachem A, Yacoub D, Gillis MA, Merhi Y. J Transl Med. 2015 May 7;13:142. doi: 10.1186/s12967-015-0508-y.
Tidjane N, Hachem A, Zaid Y, Merhi Y, Gaboury L, Girolami JP, Couture R. A primary role for kinin B1 receptor in inflammation, organ damage, and lethal thrombosis in a rat model of septic shock in diabetes. Eur J Inflamm. 2015 Apr 1;13(1):40-52.
Alturaihi H, Hassan GS, Al-Zoobi L, Salti S, Darif Y, Yacoub D, El Akoum S, Oudghiri M, Merhi Y, Mourad W. Interaction of CD154 with different receptors and its role in bidirectional signals. Eur J Immunol. 2015 Feb;45(2):592-602. doi: 10.1002/eji.201444941. Epub 2014 Dec 16.
Chondroitin sulfate coatings display low platelet but high endothelial cell adhesive properties favorable for vascular implants. Thalla PK, Fadlallah H, Liberelle B, Lequoy P, De Crescenzo G, Merhi Y, Lerouge S. Biomacromolecules. 2014 Jul 14;15(7):2512-20. doi: 10.1021/bm5003762. Epub 2014 Jun 25.
Chan-Chan LH, Vargas-Coronado RF, Cervantes-Uc JM, Cauich-Rodríguez JV, Rath R, Phelps EA, García AJ, San Román Del Barrio J, Parra J, Merhi Y, Tabrizian M. Platelet adhesion and human umbilical vein endothelial cell cytocompatibility of biodegradable segmented polyurethanes prepared with 4,4'-methylene bis(cyclohexyl isocyanate), poly(caprolactone) diol and butanediol or dithioerythritol as chain extenders. J Biomater Appl. 2013 Aug;28(2):270-7. doi: 10.1177/0885328212448259. Epub 2012 Jun 7.
Bou Khzam L, Hachem A, Zaid Y, Boulahya R, Mourad W, Merhi Y. Soluble CD40 ligand impairs the anti-platelet function of peripheral blood angiogenic outgrowth cells via increased production of reactive oxygen species. Thromb Haemost. 2013 May;109(5):940-7. doi: 10.1160/TH12-09-0679. Epub 2013 Feb 21.
Hassan GS, Yacoub D, Alaaeddine N, Nadiri A, Merhi Y, Mourad W. CD154: the atherosclerotic risk factor in rheumatoid arthritis? Arthritis Res Ther. 2013 Feb 22;15(1):206. doi: 10.1186/ar4153. Review.
Thalla PK, Contreras-García A, Fadlallah H, Barrette J, De Crescenzo G, Merhi Y, Lerouge S. A versatile star PEG grafting method for the generation of nonfouling and nonthrombogenic surfaces. Biomed Res Int. 2013;2013:962376. doi: 10.1155/2013/962376. Epub 2012 Dec 20.
Bou Khzam L, Boulahya R, Abou-Saleh H, Hachem A, Zaid Y, Merhi Y. Soluble CD40 ligand stimulates the pro-angiogenic function of peripheral blood angiogenic outgrowth cells via increased release of matrix metalloproteinase-9.PLoS One. 2013 Dec 16;8(12):e84289. doi: 10.1371/journal.pone.0084289. eCollection 2013.
Hachem A, Yacoub D, Zaid Y, Mourad W, Merhi Y. Involvement of nuclear factor κB in platelet CD40 signaling. Biochem Biophys Res Commun. 2012 Aug 17;425(1):58-63. doi: 10.1016/j.bbrc.2012.07.049. Epub 2012 Jul 20.
El Fakhry Y, Alturaihi H, Yacoub D, Liu L, Guo W, Leveillé C, Jung D, Khzam LB, Merhi Y, Wilkins JA, Li H, Mourad W. Functional interaction of CD154 protein with α5β1 integrin is totally independent from its binding to αIIbβ3 integrin and CD40 molecules. J Biol Chem. 2012 May 25;287(22):18055-66. doi: 10.1074/jbc.M111.333989. Epub 2012 Mar 29.
Hassan GS, Merhi Y, Mourad W. CD40 ligand: a neo-inflammatory molecule in vascular diseases. Immunobiology. 2012 May;217(5):521-32. doi: 10.1016/j.imbio.2011.03.010. Epub 2011 Apr 7. Review.
laboratory of Thrombosis and Hemostasis, S-4600
Montreal Heart Institute
5000, Belanger
Montreal, Québec, Canada
H1T1C8
yahye.merhi@icm-mhi.org
Lab.: 514-376-3330 # 3035
Cell.: 514-262-1009
Team members
Yahye Merhi, Ph. D., Director, yahye.merhi@icm-mhi.org, 514-376-3330 # 3035
Souhad El Akoum, Ph.D., Postdoc fellow, elakoum_souhad@hotmail.com, 514-376-3330 #3155
Kevin Kojok, Ph.D. student, kevin.kojok@outlook.com
Rahma Boulahya, Ph.D. student in collaboration with Dr Marie Lordkipanidzé's lab, rahma.mrad@gmail.com
Mourad Dandachli, Master's degree student in collaboration with Dr. Walid Mouras' lab at the CRCHUM, mourad.dandachli@umontreal.ca
Research projects
Heart disease can be caused by multiple risk factors, which cause inflammation by activating blood cells, and damage blood vessels. Unfortunately, current interventions and drug treatments do not prevent completely or limit the progression and the occurrence of narrowed and blocked heart blood vessels. Actually, a subset of progenitor cells called endothelial progenitor cells have shown promising results in repairing the damaged arteries and in limiting the reactions of platelets, the principal blood cells involved in blood clots. However, some inflammatory molecules in blood, such as CD40 ligand, may affect platelets and the function of endothelial progenitior cells and their capacity to reduce blood clot formation.
Our research program aims to study and to understand the mechanisms at work in the crosstalk between platelets and endothelial progenitor cells in thrombosis or blood clot formation and how these reactions are affected by the inflammatory molecule CD40 ligand. We will address the central hypothesis that CD40 ligand activates platelets and reduces the function of endothelial progenitor cells, which results in enhanced platelet reactivity and blood clot formation.
Our strategy includes in vitro study with isolated blood cells and in vivo study with clinically relevant animal models of heart vessel disease.
This research program is largely based on a new concept that CD40 ligand is a thrombo-inflammatory molecule that, with its receptor CD40 on platelets and endothelial progenitor cells, plays an important role in thrombosis. This concept is innovative in the field of vascular biology, thrombosis and hemostasis. Our laboratory was the first to highlight this concept, both at the cellular and pharmacological levels, in several publications We are addressing new important original questions and proposing established and innovative approaches to reveal new basic mechanisms in platelet function and endothelial progenitor cell biology, which are relevant for understanding the process of thrombosis and vessel narrowing. These insights should enable us to identify new drugs and to the discovery of innovative therapeutic options in the clinical management of coronary heart diseases.
Publications
For complete list of publications
Bou Khzam L, Bouchereau O, Boulahya R, Hachem A, Zaid Y, Abou-Saleh H, Merhi Y. Early outgrowth cells versus endothelial colony forming cells functions in platelet aggregation. J Transl Med. 2015 Nov 9;13:353. doi: 10.1186/s12967-015-0723-6.
Noel S, Hachem A, Merhi Y, De Crescenzo G. Development of a Polyester Coating Combining Antithrombogenic and Cell Adhesive Properties: Influence of Sequence and Surface Density of Adhesion Peptides. Biomacromolecules. 2015 Jun 8;16(6):1682-94. doi: 10.1021/acs.biomac.5b00219. Epub 2015 May 4.
Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent manner. Abou-Saleh H, Hachem A, Yacoub D, Gillis MA, Merhi Y. J Transl Med. 2015 May 7;13:142. doi: 10.1186/s12967-015-0508-y.
Tidjane N, Hachem A, Zaid Y, Merhi Y, Gaboury L, Girolami JP, Couture R. A primary role for kinin B1 receptor in inflammation, organ damage, and lethal thrombosis in a rat model of septic shock in diabetes. Eur J Inflamm. 2015 Apr 1;13(1):40-52.
Alturaihi H, Hassan GS, Al-Zoobi L, Salti S, Darif Y, Yacoub D, El Akoum S, Oudghiri M, Merhi Y, Mourad W. Interaction of CD154 with different receptors and its role in bidirectional signals. Eur J Immunol. 2015 Feb;45(2):592-602. doi: 10.1002/eji.201444941. Epub 2014 Dec 16.
Chondroitin sulfate coatings display low platelet but high endothelial cell adhesive properties favorable for vascular implants. Thalla PK, Fadlallah H, Liberelle B, Lequoy P, De Crescenzo G, Merhi Y, Lerouge S. Biomacromolecules. 2014 Jul 14;15(7):2512-20. doi: 10.1021/bm5003762. Epub 2014 Jun 25.
Chan-Chan LH, Vargas-Coronado RF, Cervantes-Uc JM, Cauich-Rodríguez JV, Rath R, Phelps EA, García AJ, San Román Del Barrio J, Parra J, Merhi Y, Tabrizian M. Platelet adhesion and human umbilical vein endothelial cell cytocompatibility of biodegradable segmented polyurethanes prepared with 4,4'-methylene bis(cyclohexyl isocyanate), poly(caprolactone) diol and butanediol or dithioerythritol as chain extenders. J Biomater Appl. 2013 Aug;28(2):270-7. doi: 10.1177/0885328212448259. Epub 2012 Jun 7.
Bou Khzam L, Hachem A, Zaid Y, Boulahya R, Mourad W, Merhi Y. Soluble CD40 ligand impairs the anti-platelet function of peripheral blood angiogenic outgrowth cells via increased production of reactive oxygen species. Thromb Haemost. 2013 May;109(5):940-7. doi: 10.1160/TH12-09-0679. Epub 2013 Feb 21.
Hassan GS, Yacoub D, Alaaeddine N, Nadiri A, Merhi Y, Mourad W. CD154: the atherosclerotic risk factor in rheumatoid arthritis? Arthritis Res Ther. 2013 Feb 22;15(1):206. doi: 10.1186/ar4153. Review.
Thalla PK, Contreras-García A, Fadlallah H, Barrette J, De Crescenzo G, Merhi Y, Lerouge S. A versatile star PEG grafting method for the generation of nonfouling and nonthrombogenic surfaces. Biomed Res Int. 2013;2013:962376. doi: 10.1155/2013/962376. Epub 2012 Dec 20.
Bou Khzam L, Boulahya R, Abou-Saleh H, Hachem A, Zaid Y, Merhi Y. Soluble CD40 ligand stimulates the pro-angiogenic function of peripheral blood angiogenic outgrowth cells via increased release of matrix metalloproteinase-9.PLoS One. 2013 Dec 16;8(12):e84289. doi: 10.1371/journal.pone.0084289. eCollection 2013.
Hachem A, Yacoub D, Zaid Y, Mourad W, Merhi Y. Involvement of nuclear factor κB in platelet CD40 signaling. Biochem Biophys Res Commun. 2012 Aug 17;425(1):58-63. doi: 10.1016/j.bbrc.2012.07.049. Epub 2012 Jul 20.
El Fakhry Y, Alturaihi H, Yacoub D, Liu L, Guo W, Leveillé C, Jung D, Khzam LB, Merhi Y, Wilkins JA, Li H, Mourad W. Functional interaction of CD154 protein with α5β1 integrin is totally independent from its binding to αIIbβ3 integrin and CD40 molecules. J Biol Chem. 2012 May 25;287(22):18055-66. doi: 10.1074/jbc.M111.333989. Epub 2012 Mar 29.
Hassan GS, Merhi Y, Mourad W. CD40 ligand: a neo-inflammatory molecule in vascular diseases. Immunobiology. 2012 May;217(5):521-32. doi: 10.1016/j.imbio.2011.03.010. Epub 2011 Apr 7. Review.
Contact
laboratory of Thrombosis and Hemostasis, S-4600
Montreal Heart Institute
5000, Belanger
Montreal, Québec, Canada
H1T1C8
yahye.merhi@icm-mhi.org
Lab.: 514-376-3330 # 3035
Cell.: 514-262-1009