Mansoor Husain

Research Synopsis

Keywords: diabetes, heart failure, vascular biology, transgenic mouse models of cardiovascular disease.

Areas of Focus:

Molecular regulation of vascular smooth muscle cell proliferation & differentiation.

Tissue-specific transgene regulation informs molecular pathophysiology.

Genetic and experimental models of cardiovascular disease.

Clinical and experimental cardiovascular imaging.

Acute cardiac care.

We are focused on elucidating the molecular bases of cardiovascular diseases such as hypertension, atherosclerosis and heart failure, with a particular emphasis on identifying therapeutic targets involved in pathophysiology and a mechanism underlying the cardiovascular complications of diabetes. Our approaches encompass both cell culture-based experimental systems and tissue-specific transgenic mouse models of human cardiovascular disease.

More specifically, we study the transcriptional and post-translational regulation of cell cycle- and Ca2+-regulatory genes in vascular smooth muscle cells, and the impact of molecular genetic manipulations of these pathways on both the proliferative and contractile phenotypes of vascular smooth muscle cells. We are also interested in defining the roles played by certain vasoactive hormones, enzymes and their downstream signaling pathways in inflammatory disease of the heart and circulatory system. More recently, we have begun to characterize and optimize an in vitro system for the differentiation of fully functional smooth muscle cells and cardiac myocytes from embryonic stem cells, with a view to employ these cells in disease modeling and/or regenerative therapies.

We have an active research program on the biological effects of incretin targeted therapies for diabetes on the cardiovascular system. We also participate in select international and national clinical trials in this field.

Recent Publications

Selected list of publications:

Cameron-Vendrig A, Reheman A, Siraj MA, Xu XR, Wang Y, Lei X, Afroze T, Shikatani E, El-Mounayri O, Noyan H, Weissleder R, Ni H, Husain M. Glucagon-like peptide-1 receptor activation attenuates platelet aggregation and thrombosis. Diabetes. 2016 Mar 2. Senior Responsible Author.

Noyan H, El-Mounayri O, Isserlin R, Arab S, Momen A, Cheng HS, Wu J, Afroze T, Li RK, Fish JE, Bader GD, Husain M. Cardioprotective Signature of Short-Term Caloric Restriction. PLoS One. 2015 Jan 1;10(6):e0130658. Senior Responsible Author.

Afroze T, Yang G, Khoshbin A, Tanwir M, Tabish T, Momen A, Husain M. Calcium Efflux Activity of Plasma Membrane Ca2+ ATPase-4 (PMCA4) Mediates Cell Cycle Progression in Vascular Smooth Muscle Cells. J Biol Chem. 2014 Mar 7;289(10):7221-31. Available from: http://www.jbc.org/content/early/2014/01/21/jbc.M113.533638.abstract. Senior Responsible Author.

Noyan-Ashraf MH, Shikatani EA, Schuiki I, Mukovozov IM, Wu J, Li RK, Volchuk A, Robinson LL, Billia F, Drucker DJ, Husain M. A glucagon-like peptide-1 analogue reverses the molecular pathology and cardiac dysfunction of a mouse model of obesity. Circulation. 2013 Jan;127(1):74-85. Epub 2012 Nov 27. (Trainee publication, Supervisor of Shikatani). Senior Responsible Author.

Ishida M, El-Mounayri O, Kattman S, Zandstra P, Sakamoto H, Ogawa M, Keller G, Husain M. Regulated expression and role of c-Myb in the cardiovascular-directed differentiation of mouse embryonic stem cells. Circ Res 2012 Jan 20; 100: 253-64. Epub 2011 Nov 23. (Trainee publication, Supervisor of Ishida, El-Mounayri). Senior Responsible Author.

Hui S, Choi J, Zaidi S, Momen A, Steinbach SK, Sadi AM, Ban K, Husain M. Peptide-mediated disruption of calmodulin-cyclin E interactions inhibits proliferation of vascular smooth muscle cells and neointima formation. Circ Res Apr 29, 2011; 108(9):1053-62.Epub 2011 Mar (Trainee publication, Supervisor of Hui, Choi, Zaidi, Momen, Steinbach, Sadi and Ban). Senior Responsible Author.

Zaidi SH, Huang Q, Momen A, Riazi A, Husain M. Growth Differentiation Factor 5 (Bone Morphogenetic Protein 14) regulates cardiac repair after myocardial infarction. J Am Coll Cardiol 2010 Jan; 55 (2):135-43. Senior Responsible Author.

Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. Cardioprotective and vasodilatory actions of GLP-1 receptor are mediated through both GLP-1 receptor-dependent and independent pathways. Circulation 2008 May 6; 117(18): 2340-50. (Trainee publication, Supervisor of Ban, Noyan Ashraf, Hoefer). Senior Responsible Author.

Yang L, Kabir G, Gros R, El-Moselhi A, Husain M, Stewart D. Conditional cardiac-specific over-expression of ET-1 in transgenic mice results in an inflammatory cardiomyopathy and heart failure. Circulation 2004; 109(2): 255-261. (Trainee publication, Corresponding and Co-Senior Author, Supervisor of Yang, Kabir, Gros, El-Moselhi). Senior Responsible Author.