The Frangogiannis laboratory studies the molecular mechanisms and cellular effectors involved in cardiac repair, remodeling and fibrosis. Over the last 25 years, we have published >200 manuscripts in high impact journals, dissecting inflammatory reparative and fibrogenic pathways in the injured heart. Our goal is to develop novel therapeutic strategies to attenuate inflammatory injury, improve repair and inhibit fibrosis in patients with myocardial infarction or heart failure. The laboratory focuses on several directions:

1. Regulation of the inflammatory response in infarcted and failing hearts. Current studies are focused on the role, heterogeneity and mechanisms of activation of macrophages.
2. The role of the extracellular matrix as a signaling hub in the infarcted and remodeling heart.
3. Activation and role of integrin-mediated pathways in macrophages and fibroblasts.
4. Origin, fate and mechanisms of activation of fibroblasts in myocardial disease.
5. The role of pericytes in cardiac pathology,
6. Regulation of the TGF-beta superfamily in cardiac homeostasis and disease.

M Bujak, G Ren, HJ Kweon, M Dobaczewski, A Reddy, G Taffet, XF Wang, and NG Frangogiannis. Essential Role of Smad3 in Infarct Healing and in the Pathogenesis of Cardiac Remodeling. Circulation 2007; 116:2127-38.

P Huebener, T Abou-Khamis, P Zymek, M Bujak, Ying X, K Chatila, S Haudek, G Thakker, and NG Frangogiannis, CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. J Immunol 2008; 180:2625-33.

M Bujak, HJ Kweon, K Chatila, N Li, G Taffet and NG Frangogiannis. Aging-related defects are associated with adverse cardiac remodeling in a mouse model of reperfused myocardial infarction. J Am Coll Cardiol 2008; 51:1384-92.

M Bujak, M Dobaczewski, K Chatila, L Mendoza, N Li, A Reddy, and NG Frangogiannis. Interleukin-1 type (IL-1RI) signaling critically regulates infarct healing and cardiac remodeling. Am J Pathol 2008; 173:57-67.

M Bujak, M Dobaczewski, C Gonzalez-Quesada, Y Xia, T Leucker, P Zymek, V Veeranna, A Tager, A Luster, and NG Frangogiannis. Induction of the CXC Chemokine Interferon-g-Inducible Protein (IP)-10 Regulates the Reparative Response Following Myocardial Infarction. Circ Res2009; 105:973-83.

M Dobaczewski, Y Xia, M Bujak, C Gonzalez-Quesada, and NG Frangogiannis. CCR5 signaling suppresses inflammation and reduces adverse remodeling following myocardial infarction mediating recruitment of regulatory T cells. Am J Pathol 2010; 176: 2177-87.

M Dobaczewski, M Bujak, N Li, C Gonzalez-Quesada; LH Mendoza, XF Wang, and NG Frangogiannis. Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circ Res 2010; 107 (3): 418-28.

Y Xia, M Dobaczewski, C Gonzalez-Quesada, W Chen, A Biernacka, N Li, D Lee and NG Frangogiannis. Endogenous Thrombospondin-1 protects the pressure-overloaded myocardium by modulating fibroblast phenotype and matrix metabolism. Hypertension 2011; 58: 902-911.

NG Frangogiannis. Regulation of the inflammatory response in cardiac repair. Circ Res 2012: 110: 159-173.

NG Frangogiannis. Matricellular proteins in cardiac adaptation and disease. Physiol Rev 2012; 92:635-688.

W Chen, A Saxena, N Li, J Sun, DW Lee, Q Tian, M Dobaczewski and NG Frangogiannis. Endogenous IRAK-M attenuates post-infarction remodeling through effects on macrophages and fibroblasts. Arterioscl Thromb Vasc Biol 2012; 32:2598-608.

P Kong, C Gonzalez-Quesada, N Li, M Cavalera, D-W Lee and NG Frangogiannis. Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation. Am J Physiol Endocrinol Metab 2013; 305:E439-450.

P Kong, P Christia, A Saxena, Y Su and NG Frangogiannis. Lack of specificity of Fibroblast Specific Protein (FSP)1 in cardiac remodeling and fibrosis. Am J Physiol Heart Circ Physiol 2013;305(9):H1363-72.

A Saxena, W Chen, Y Su, V Rai, OU Uche, N Li, and NG Frangogiannis. IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium. J Immunol 2013; 191(9):4838-48.

C Gonzalez-Quesada, M Cavalera, A Biernacka, P Kong, DW Lee, A Saxena, O Frunza, M Dobaczewski, AV Shinde, and NG Frangogiannis. Thrombospondin-1 induction in the diabetic myocardium stabilizes the cardiac matrix while promoting vascular rarefaction through angiopoietin-2 upregulation. Circ Res 2013; 113(12):1331-44.

NG Frangogiannis. The inflammatory response in myocardial injury, repair and remodeling. Nat Rev Cardiol 2014; 11:255-265.

A Saxena, M Bujak, O Frunza, M Dobaczewski, C Gonzalez-Quesada, B Lu, C Gerard and NG Frangogiannis. CXCR3-independent actions of the CXC chemokine CXCL10 in the infarcted myocardium and in isolated cardiac fibroblasts are mediated through proteoglycans. Cardiovasc Res 2014; 103:217-227. 

M Cavalera, J Wang and NG Frangogiannis. Obesity, metabolic dysfunction and cardiac fibrosis: pathophysiologic pathways, molecular mechanisms and therapeutic opportunities. Transl Res 2014; 164:323-335.

A Saxena, M Dobaczewski, V Rai, Z Haque, W Chen, N Li, and NG Frangogiannis. Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function. Am J Physiol Heart Circ Physiol 2014; 307(8):H1233-42.

A Biernacka, M Cavalera, J Wang, I Russo, A Shinde, P Kong, C Gonzalez-Quesada, V Rai, M Dobaczewski, DW Lee, XF Wang and NG Frangogiannis. Smad3 signaling promotes fibrosis, while preserving cardiac and aortic geometry in obese diabetic mice. Circ Heart Fail 2015; 8: 788-798.

O Frunza, I Russo, A Saxena, AV Shinde, C Humeres, W Hanif, V Rai, Y Su, and NG Frangogiannis. Myocardial galectin-3 expression is associated with remodeling of the pressure-overloaded heart and may delay the hypertrophic response, without affecting survival, dysfunction, and cardiac fibrosis. Am J Pathol 2016; 186:1114-27.

S Prabhu, and NG Frangogiannis. The cell biological basis of cardiac repair: from inflammation to fibrosis. Circ Res 2016: 119:91-112.

AV Shinde, C Humeres, and NG Frangogiannis. The role of α-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling. BBA Mol Bas Dis 2017; 1863: 298-309.

NG Frangogiannis. The extracellular matrix in myocardial injury, repair and remodeling. J Clin Invest 2017; 127: 1600-1612.

AV Shinde, M Dobaczewski, JJ De Haan, A Saxena, KK Lee, Y Xia, W Chen, Y Su, W Hanif, IK Madahar,  VM Paulino, G Melino and NG Frangogiannis. Tissue transglutaminase induction in the pressure-overloaded myocardium regulates cardiac remodeling. Cardiovasc Res 2017; 113:892-905.

P Kong, A Shinde, Y Su, I Russo, B Chen, A Saxena, SJ Conway, JM Graff and NG Frangogiannis. Opposing actions of fibroblast and cardiomyocyte Smad3 signaling in the infarcted myocardium. Circulation 2018 Feb 13;137(7):707-724.

S Huang, and NG Frangogiannis. Anti-inflammatory therapies in myocardial infarction: failures, hopes and challenges. Br J Pharmacol 2018; 175:1377-1400.

AV Shinde, Y Su, BA Palanski, K Fujikura, MJ Garcia, and NG Frangogiannis. Pharmacologic inhibition of the enzymatic effects of tissue transglutaminase reduces cardiac fibrosis and attenuates cardiomyocyte hypertrophy following pressure overload. J Mol Cell Cardiol 2018; 117: 36-48.

L Alex, I Russo, V Holoborodko, and NG Frangogiannis. Characterization of a mouse model of obesity-related fibrotic cardiomyopathy that recapitulates features of human Heart Failure with Preserved Ejection Fraction. Am J Physiol Heart Circ Physiol 2018; 315:H934-949.

I Russo, M Cavalera, S Huang, Y Su, A Hanna, B Chen, AV Shinde, SJ Conway, JM Graff, and NG Frangogiannis. Protective effects of activated myofibroblasts in the pressure-overloaded myocardium are mediated through Smad-dependent activation of a matrix-preserving program.  Circ Res 2019; 124: 1214-1227.

S Huang, B Chen, Y Su, L Alex, C Humeres, AV Shinde, SJ Conway, and NG Frangogiannis. Distinct roles of myofibroblast-specific Smad2 and Smad3 signaling in repair and remodeling of the infarcted heart. J Mol Cell Cardiol 2019; 132:84-97.

B Chen, S Huang, Y Su, Y-J Wu, A Hanna, A Brickshawana, JM Graff, and NG Frangogiannis. Macrophage Smad3 protects the infarcted heart, stimulating phagocytosis and regulating inflammation. Circ Res 2019; 125: 55-70.

NG Frangogiannis. The extracellular matrix in ischemic and non-ischemic heart failure. Circ Res 2019; 125: 117-146.

C Humeres and NG Frangogiannis. Fibroblasts in the infarcted, remodeling and failing heart. JACC Basic Transl Res. 2019; 4:449-467.

NG Frangogiannis . Transforming Growth Factor (TGF)-b in tissue fibrosis. J Exp Med 2020;217 (3): e20190103 https://doi.org/10.1084/jem.20190103.

NG Frangogiannis, JC Covacic. Extracellular matrix in Ischemic Heart Disease. Part 4/4: JACC Focus Seminar. J Am Coll Cardiol 2020 75(17):2219-2235.

LE de Castro Bras and NG Frangogiannis. Extracellular matrix-derived peptides in tissue remodeling and fibrosis. Matrix Biol 2020; 91-92:176-187.

A Hanna, AV Shinde and NG Frangogiannis. Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of non-reperfused myocardial infarction. Am J Physiol Heart Circ Physiol. 2020 Nov 1;319(5):H948-H964.

NG Frangogiannis. Cardiac Fibrosis. Cardiovasc Res 2021 May 25: 117(6):1450-1488.

I Tuleta and NG Frangogiannis. Diabetic fibrosis. BBA Mol Bas Dis. 2021 Apr 1, 1867 (4):166044. doi doi: 10.1016/j.bbadis.2020.166044

C Humeres, AV Shinde, A Hanna, L Alex, SC Hernandez, R Li, B Chen, SJ Conway, and NG Frangogiannis. Smad7 effects on TGF-beta and Erbb2 restrain myofibroblast activation and protect from post-infarction heart failure. J Clin Invest 2022 Feb 1;132(3):e146926. doi: 10.1172/JCI146926.

NG Frangogiannis. Transforming growth factor-b in myocardial disease. Nat Rev Cardiol 2022; 19: 435-455.

NG Frangogiannis. Why animal models are lost in translation. J Cardiovasc Aging2022 Apr 2(2): 22. doi: 10.20517/jca.2022.10. Epub 2022 Mar 31.

J Li, R Li, I Tuleta, SC Hernandez. C Humeres, A Hanna, B Chen, and NG Frangogiannis. The role of endogenous Smad7 in regulating macrophage phenotype and function following myocardial infarction. FASEB J 2022 Jul 36(7) e22400.

B Chen, R Li, SC Hernandez, A Hanna, K Su, AV Shinde, and NG Frangogiannis. Differential effects of Smad2 and Smad3 in regulation of macrophage phenotype and function in the infarcted myocardium. J Mol Cell Cardiol 2022; 171: 1-15.

R Li and NG Frangogiannis. Integrins in cardiac fibrosis. J Mol Cell Cardiol 2022; 172:1-13.

A Kubota and NG Frangogiannis. Macrophages in myocardial infarction. Am J Physiol Cell Physiol 2022 Oct 1;323(4):C1304-C1324. doi: 10.1152/ajpcell.00230.2022. Epub 2022 Sep 12.

L Alex, I Tuleta, A Hanna, and NG Frangogiannis. Diabetes induces cardiac fibroblast activation, promoting a matrix-preserving non-myofibroblast phenotype, without stimulating pericyte to fibroblast conversion. J Am Heart Association 2023 ;12(6):e027463. doi: 10.1161/JAHA.122.027463.

L Alex, I Tuleta, SC Hernandez, A Hanna, H Venugopal, M Astorkia, C Humeres, A Kubota, K Su, D Zheng, and NG Frangogiannis. Cardiac pericytes acquire a fibrogenic phenotype and contribute to vascular maturation after myocardial infarction. Circulation 2023 12;148(11):882-898. doi: 10.1161/CIRCULATIONAHA.123.064155.

R Li, B Chen, A Kubota, A Hanna, C Humeres, SC Hernandez, Y Liu, R Ma, I Tuleta, S Huang, H Venugopal, F Zhu, K Su, J Li, J Zhang, D Zheng, and NG Frangogiannis. Protective effects of macrophage-specific integrin alpha5 in myocardial infarction are associated with accentuated angiogenesis. Nat Commun 2023; Nov 20;14(1):7555. doi: 10.1038/s41467-023-43369-x.

NG Frangogiannis. The fate and role of the pericytes in myocardial diseases. Eur J Clin Invest 2024; 2024 Aug;54(8):e14204. doi: 10.1111/eci.14204.

I Hilgendorf, S Frantz and NG Frangogiannis. Repair of the Infarcted Heart: Cellular effectors, molecular mechanisms and therapeutic opportunities. Circ Res 2024 Jun 7;134(12):1718-1751. doi: 10.1161/CIRCRESAHA.124.323658.

C Humeres, AV Shinde, I Tuleta, SC Hernandez, A Hanna, S Huang, H Venugopal, JT Aguilan, SJ Conway, S Sidoli, and NG Frangogiannis. Fibroblast Smad7 protects the remodeling pressure-overloaded heart. Circ Res. 2024 Jul 19;135(3):453-469. doi: 10.1161/CIRCRESAHA.123.323360. Epub 2024 Jun 20.

R Li, A Hanna, S Huang, SC Hernandez, I Tuleta, A Kubota, C Humeres, B Chen, Y Liu, D Zheng, and NG Frangogiannis. Macrophages in the infarcted heart acquire a fibrogenic phenotype, expressing matricellular proteins, but do not undergo fibroblast conversion. J Mol Cell Cardiol 2024 Nov:196:152-167. doi: 10.1016/j.yjmcc.2024.07.010. Epub 2024 Jul 31.235.

NG Frangogiannis. Targeting metabolically activated fibroblasts in the failing heart. Nat Cardiovasc Res 2024 Jul;3(7):782-784 doi: 10.1038/s44161-024-00500-5.

I Tuleta, A Hanna, C Humeres, JT Aguilan, S Sidoli, F Zhu and NG Frangogiannis. Fibroblast-specific TGF-b signaling mediates cardiac dysfunction, fibrosis and hypertrophy in obese diabetic mice. Cardiovasc Res 2024 Dec 14;120(16):2047-2063. doi: 10.1093/cvr/cvae210.

NG Frangogiannis. Targeting macrophage-fibroblast interactions in the failing heart. Nat Rev Cardiol. 2024 Dec 16. doi: 10.1038/s41569-024-01112-z. Online ahead of print.

Link to publications:
https://pubmed.ncbi.nlm.nih.gov/?term=frangogiannis&sort=pubdate&size=200

Link to active NIH grants:
https://reporter.nih.gov/search/76ES_yzaG0uXLwG3B097Zw/projects?projects=Active