I have a profound passion for dissecting the cellular mechanisms and molecular signals driving the pathogenesis of cardiac remodeling, in order to identify novel therapeutic targets for heart failure patients. Our research focuses on exploring the cell biological and molecular mechanisms that regulate post-infarction cardiac remodeling and the development of heart failure. We use cell-specific gene knockout mouse models and induce cardiac injury through microscopic coronary occlusion or aortic constriction surgeries followed by cardiac functional studies. We employ state-of-the-art in vivo and in vitro techniques and bioinformatics to investigate the cellular and molecular effects of our genetic interventions, including a repertoire of histopathologic techniques, AI-based quantification, in vitro genetic loss of function models, and omics approaches. 

Our published studies explored the role of TGF-beta-Smad2/3 signaling cascades in cardiac remodeling following injury (Circ Res 2019, JCI 2022, FASEBJ 2022, JMCC 2022), the in vivo MI environment that results in cardiac rupture (AJP-Heart 2020), and the protease-dependent and -independent mechanisms of collagen degradation following myocardial infarction (Matrix Biology 2021). Our most recently published work deciphered the phenotypic transition and heterogeneity of cardiac pericytes in the pathophysiologic environment of the diabetic heart (JAHA 2023), and following myocardial infarction (Circulation 2023). 

Alex L, Tuleta I, Hernandez SC, Hanna A, Venugopal H, Astorkia M, Humeres C, Kubota A, Su K, Zheng D, Frangogiannis NG. Cardiac Pericytes Acquire a Fibrogenic Phenotype and Contribute to Vascular Maturation After Myocardial Infarction. Circulation. 2023 Jun 23. doi: 10.1161/CIRCULATIONAHA.123.064155. Epub ahead of print. PMID: 37350296.

R Li, B Chen, Hanna A, Humeres C, Alex L, Frangogiannis NG. Macrophage-specific alpha 5 Integrin Signaling Protects The Infarcted Heart From Adverse Remodeling By Stimulating The Angiogenic Response. Under review in Nature Communications. 

Qin D, Jia XF, Hanna A, Lee J, Pekson R, Elord JW, Calvert JW, Frangogiannis NG, Kitsis RN. BAK contributes critically to infarct generation during reperfused myocardial infarction by promoting cardiomyocyte necrosis as well as apoptosis. Under review in JMCC.

Alex L, Tuleta I, Hanna A, Frangogiannis NG. Diabetes Induces Cardiac Fibroblast Activation, Promoting a Matrix-Preserving Nonmyofibroblast Phenotype, Without Stimulating Pericyte to Fibroblast Conversion. J Am Heart Assoc. 2023 Mar 9:e027463. doi: 10.1161/JAHA.122.027463. Epub ahead of print. PMID: 36892073.

Li J, Li R, Tuleta I, Hernandez SC, Humeres C, Hanna A, Chen B, Frangogiannis NG. The role of endogenous Smad7 in regulating macrophage phenotype following myocardial infarction. FASEB J. 2022 Jul;36(7):e22400. doi: 10.1096/fj.202101956RR. PMID: 35695814; PMCID: PMC9216182.

Venugopal H, Hanna A, Humeres C, Frangogiannis NG. Properties and Functions of Fibroblasts and Myofibroblasts in Myocardial Infarction. Cells. 2022 Apr 20;11(9):1386. doi: 10.3390/cells11091386. PMID: 35563692; PMCID: PMC9102016.

Chen B, Li R, Hernandez SC, Hanna A, Su K, Shinde AV, Frangogiannis NG. Differential effects of Smad2 and Smad3 in regulation of macrophage phenotype and function in the infarcted myocardium. J Mol Cell Cardiol. 2022 Oct;171:1-15. doi: 10.1016/j.yjmcc.2022.06.009. Epub 2022 Jul 1. PMID: 35780861.

Humeres C, Shinde AV, Hanna A, Alex L, Hernández SC, Li R, Chen B, Conway SJ, Frangogiannis NG. Smad7 effects on TGF-β and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure. J Clin Invest. 2022 Feb 1;132(3):e146926. doi: 10.1172/JCI146926. PMID: 34905511. 

Hanna A, Shinde AV, Li R, Alex L, Humeres C, Balasubramanian P, Frangogiannis NG. Collagen denaturation in the infarcted myocardium involves temporally distinct effects of MT1-MMP-dependent proteolysis and mechanical tension. Matrix Biol. 2021 May;99:18-42. doi: 10.1016/j.matbio.2021.05.005. Epub 2021 May 25. PMID: 34048934; PMCID: PMC8591556.

Hanna A, Humeres C, Frangogiannis NG. The role of Smad signaling cascades in cardiac fibrosis. Cell Signal. 2021 Jan;77:109826. doi: 10.1016/j.cellsig.2020.109826. Epub 2020 Nov 5. PMID: 33160018; PMCID: PMC7727442.

Hanna A, Shinde AV, Frangogiannis NG. Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of nonreperfused myocardial infarction. Am J Physiol Heart Circ Physiol. 2020 Nov 1;319(5):H948-H964. doi: 10.1152/ajpheart.00318.2020. Epub 2020 Sep 4. PMID: 32886000; PMCID: PMC7701358.

Hanna A , Frangogiannis NG. Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure. Cardiovasc Drugs Ther. 2020 Dec;34(6):849-863. doi: 10.1007/s10557-020-07071-0. Epub 2020 Sep 9. PMID: 32902739; PMCID: PMC7479403.

Huang S, Chen B, Humeres C, Alex L, Hanna A, Frangogiannis NG. The role of Smad2 and Smad3 in regulating homeostatic functions of fibroblasts in vitro and in adult mice. Biochim Biophys Acta Mol Cell Res. 2020 Jul;1867(7):118703. doi: 10.1016/j.bbamcr.2020.118703. Epub 2020 Mar 14. PMID: 32179057; PMCID: PMC7261645.

Hanna A, Frangogiannis NG. The cell biological basis for primary unloading in acute myocardial infarction. Int J Cardiol. 2019 Oct 15;293:45-47. doi: 10.1016/j.ijcard.2019.06.079. Epub 2019 Jul 2. PMID: 31296394. (Editorial)

Chen B, Huang S, Su Y, Wu YJ, Hanna A, Brickshawana A, Graff J, Frangogiannis NG. Macrophage Smad3 Protects the Infarcted Heart, Stimulating Phagocytosis and Regulating Inflammation. Circ Res. 2019 Jun 21;125(1):55-70. doi: 10.1161/CIRCRESAHA.119.315069. Epub 2019 May 16. PMID: 31092129; PMCID: PMC6681442.

Russo I, Cavalera M, Huang S, Su Y, Hanna A, Chen B, Shinde AV, Conway SJ, Graff J, Frangogiannis NG. Protective Effects of Activated Myofibroblasts in the Pressure-Overloaded Myocardium Are Mediated Through Smad-Dependent Activation of a Matrix-Preserving Program. Circ Res. 2019 Apr 12;124(8):1214-1227. doi: 10.1161/CIRCRESAHA.118.314438. PMID: 30686120; PMCID: PMC6459716.

Hanna A, Frangogiannis NG. The Role of the TGF-β Superfamily in Myocardial Infarction. Front Cardiovasc Med. 2019 Sep 18;6:140. doi: 10.3389/fcvm.2019.00140. PMID: 31620450; PMCID: PMC6760019.

Abstracts

Hanna A, Frangogiannis NG. ALK1-Mediated Smad1 Activation in a Myofibroblast Subset Protects the Infarcted Heart From Adverse Remodeling and Excessive Fibrosis. Circulation 146 (Suppl_1), A15700-A15700, AHA Scientific Sessions 2022 Oral Presentation.

Hanna A, Frangogiannis NG. Myofibroblast Smad1 activation Restrains Cardiac Fibrosis and Attenuates Post-Myocardial Infarction Adverse Remodeling.  Circulation 144 (Suppl_1), A11654-A11654, AHA Scientific Sessions 2021 ePoster and Video Presentation.

R Li, B Chen, A Hanna, C Humeres, L Alex, NG Frangogiannis. Macrophage-specific alpha 5 Integrin Signaling Protects The Infarcted Heart From Adverse Remodeling By Stimulating The Angiogenic Response. Circulation Research 129 (Suppl_1), AMP225-AMP225. AHA BCVS 2021.

C Humeres, AV Shinde, A Hanna, L Alex, S Conway, NG Frangogiannis. Endogenous Smad7 Restrains Myofibroblast Activation And Protects From Postinfarction Heart Failure By Suppressing Tgf-beta Signaling And By Directly Inhibiting Erbb2. Circulation Research 129 (Suppl_1), AMP262-AMP262. AHA BCVS 2021.

Hanna A, Frangogiannis NG. Smad1 Restrains Cardiac Fibrosis and Attenuates Post-Myocardial Infarction Adverse Remodeling. Albert Einstein College of Medicine, Department of Cardiology 2020. Oral Presentation.

Humeres C, Shinde AV, Hanna A, Conway SJ, Frangogiannis NG. Smad7 Induction in Activated Infarct Myofibroblasts Protects From Adverse Remodeling by Restraining TGF-beta-Mediated and Receptor Tyrosine Kinase Signaling. American Heart Association Scientific Sessions 2020. Poster Presentation. Circulation 142 (Suppl_3), A16793-A16793. AHA Scientific Sessions 2020.

Hanna A, Frangogiannis NG. Smad1 Attenuates Cardiac Remodeling and Restrains Fibrosis Following Myocardial Infarction. Albert Einstein College of Medicine, Department of Microbiology and Immunology 2020. Oral Presentation.