Professional Interests

Cardiovascular disease is the leading cause of death worldwide, killing ~19 million people per year. Research in my laboratory aims at discovering novel molecular mechanisms that control the activities of vascular cells – smooth muscle and endothelial cells – and are relevant for cardiovascular disease including atherosclerosis, plaque erosion, and arterial restenosis. These mechanisms may serve as basis for novel strategies to diagnose, prevent. or treat cardiovascular disease.

Using genetically modified mice, human cells and tissues, tools from molecular biology and biochemistry, metabolomics, transcriptomics, and proteomics, we are tackling important gaps of knowledge in vascular biology, including:

a)    How mitochondrial mechanisms and cell metabolic processes influence the phenotype of vascular smooth muscle cells during artery formation and in the response to arterial injury.

b)    How endothelial cell respiration maintains homeostasis of fully mature arteries and its relevance for atherosclerotic plaque erosion.

c)     How the mitochondrial form of the atypical cadherin FAT1 controls vascular smooth muscle cell metabolic reprogramming and affects atherosclerotic plaque formation.

d)    How the β-catenin C-terminal domain contributes to vascular smooth muscle cell phenotypic switching upon arterial injury and its interaction with the sphingosine-1 phosphate signaling pathway.

In addition, we have been involved in the study of risk factors for cardiovascular disease, particularly obesity, and established important intramural and extramural scientific collaborations, for instance, to develop an innovative method to visualize arterial remodeling in three dimensions.

Please visit the Riascos-Bernal Lab website for furher information (see link above)

Oliveira-Paula GH, Liu S, Maira A, Ressa G, Ferreira GC, Quintar A, Jayakumar S, Almonte V, Parikh D, Valenta T, Basler K, Hla T, Riascos-Bernal DF*, Sibinga NES*. The β-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis. Sci Adv. 2024 Mar 15;10(11):eadg9278. doi: 10.1126/sciadv.adg9278. Epub 2024 Mar 13. PubMed PMID: 38478616. * Co-corresponding author

Riascos-Bernal DF*, Ressa G, Korrapati A, Sibinga NES*. The FAT1 Cadherin Drives Vascular Smooth Muscle Cell Migration. Cells. 2023 Jun 14;12(12). doi: 10.3390/cells12121621. Review. PubMed PMID: 37371091. * Co-corresponding author

Oliveira-Paula GH, I M Batista R, Stransky S, Tella SC, Ferreira GC, Portella RL, Pinheiro LC, Damacena-Angelis C, Riascos-Bernal DF, Sidoli S, Sibinga N, Tanus-Santos JE. Orally administered sodium nitrite prevents the increased α-1 adrenergic vasoconstriction induced by hypertension and promotes the S-nitrosylation of calcium/calmodulin-dependent protein kinase II. Biochem Pharmacol. 2023 Jun;212:115571. doi: 10.1016/j.bcp.2023.115571. Epub 2023 Apr 29. PubMed PMID: 37127250; PubMed Central PMCID: PMC10198929.

Chinnasamy P, Casimiro I, Riascos-Bernal DF, Venkatesh S, Parikh D, Maira A, Srinivasan A, Zheng W, Tarabra E, Zong H, Jayakumar S, Jeganathan V, Pradan K, Aleman JO, Singh R, Nandi S, Pessin JE, Sibinga NES. Increased adipose catecholamine levels and protection from obesity with loss of Allograft Inflammatory Factor-1. Nat Commun. 2023 Jan 3;14(1):38. doi: 10.1038/s41467-022-35683-7. PubMed PMID: 36596796; PubMed Central PMCID: PMC9810600.

Parikh D, Jayakumar S, Oliveira-Paula GH, Almonte V, Riascos-Bernal DF, Sibinga NES. Allograft inflammatory factor-1-like is a situational regulator of leptin levels, hyperphagia, and obesity. iScience. 2022 Oct 21;25(10):105058. doi: 10.1016/j.isci.2022.105058. eCollection 2022 Oct 21. PubMed PMID: 36134334; PubMed Central PMCID: PMC9483794.

Riascos-Bernal DF, Maira A, Sibinga NES. The Atypical Cadherin FAT1 Limits Mitochondrial Respiration and Proliferation of Vascular Smooth Muscle Cells. Front Cardiovasc Med. 2022;9:905717. doi: 10.3389/fcvm.2022.905717. eCollection 2022. Review. PubMed PMID: 35647082; PubMed Central PMCID: PMC9130956.

Becher T*, Riascos-Bernal DF*, Chi J, Cohen P, Sibinga NES. Three-Dimensional Visualization of Atherosclerotic Vessels by Tissue Clearing and Light-Sheet Fluorescence Microscopy. Methods Mol Biol. 2022;2419:841-851. doi: 10.1007/978-1-0716-1924-7_51. PubMed PMID: 35238005. * equal contribution

Madrigal-Matute J, de Bruijn J, van Kuijk K, Riascos-Bernal DF, Diaz A, Tasset I, Martín-Segura A, Gijbels MJJ, Sander B, Kaushik S, Biessen EAL, Tiano S, Bourdenx M, Krause GJ, McCracken I, Baker AH, Jin H, Sibinga NES, Bravo-Cordero JJ, Macian F, Singh R, Rensen PCN, Berbée JFP, Pasterkamp G, Sluimer JC, Cuervo AM. Protective role of chaperone-mediated autophagy against atherosclerosis. Proc Natl Acad Sci U S A. 2022 Apr 5;119(14):e2121133119. doi: 10.1073/pnas.2121133119. PubMed PMID: 35363568.

Riascos-Bernal DF, Sibinga NE. Neutrophil extracellular traps in cardiac hypertrophy: a KLF2 perspective. J Clin Invest. 2022 Feb 1;132(3). doi: 10.1172/JCI156453. PubMed PMID: 35104806; PubMed Central PMCID: PMC8803320.

Almonte VM, Uriyanghai U, Egaña-Gorroño L, Parikh D, Oliveira-Paula GH, Zhang J, Jayakumar S, Riascos-Bernal DF, Sibinga NES. PLX3397, a CSF1 receptor inhibitor, limits allotransplantation-induced vascular remodeling. Cardiovasc Res. 2021 Sep 3;. doi: 10.1093/cvr/cvab289. [Epub ahead of print] PubMed PMID: 34478521.

Chen W, Fitzpatrick J, Sozio SM, Jaar BG, Estrella MM, Riascos-Bernal DF, Wu TT, Qiu Y, Kurland IJ, Dubin RF, Chen Y, Parekh RS, Bushinsky DA, Sibinga NES. Identification of Novel Biomarkers and Pathways for Coronary Artery Calcification in Nondiabetic Patients on Hemodialysis Using Metabolomic Profiling. Kidney360. 2021 Feb;2(2):279-289. doi: 10.34067/kid.0004422020. PubMed PMID: 34723191; PubMed Central PMCID: PMC8553022.

Riascos-Bernal DF. Perking Up Strategies to Control Restenosis. JACC Basic Transl Sci. 2020 Mar;5(3):264-266. doi: 10.1016/j.jacbts.2020.01.013. eCollection 2020 Mar. PubMed PMID: 32215377; PubMed Central PMCID: PMC7091502.

Becher T*, Riascos-Bernal DF*, Kramer DJ, Almonte VM, Chi J, Tong T, Oliveira-Paula GH, Koleilat I, Chen W, Cohen P, Sibinga NES. Three-Dimensional Imaging Provides Detailed Atherosclerotic Plaque Morphology and Reveals Angiogenesis After Carotid Artery Ligation. Circ Res. 2020 Feb 28;126(5):619-632. doi: 10.1161/CIRCRESAHA.119.315804. Epub 2020 Jan 9. PubMed PMID: 31914850; PubMed Central PMCID: PMC7047629. * equal contribution and co-corresponding author

Parikh D, Riascos-Bernal DF, Egaña-Gorroño L, Jayakumar S, Almonte V, Chinnasamy P, Sibinga NES. Allograft inflammatory factor-1-like is not essential for age dependent weight gain or HFD-induced obesity and glucose insensitivity. Sci Rep. 2020 Feb 27;10(1):3594. doi: 10.1038/s41598-020-60433-4. PubMed PMID: 32107417; PubMed Central PMCID: PMC7046694.

Egaña-Gorroño L, Chinnasamy P, Casimiro I, Almonte VM, Parikh D, Oliveira-Paula GH, Jayakumar S, Law C, Riascos-Bernal DF, Sibinga NES. Allograft inflammatory factor-1 supports macrophage survival and efferocytosis and limits necrosis in atherosclerotic plaques. Atherosclerosis. 2019 Oct;289:184-194. doi: 10.1016/j.atherosclerosis.2019.07.022. Epub 2019 Jul 26. PubMed PMID: 31439353; PubMed Central PMCID: PMC7048374.

Wang Y, Lu P, Wu B, Riascos-Bernal DF, Sibinga NES, Valenta T, Basler K, Zhou B. Myocardial β-Catenin-BMP2 signaling promotes mesenchymal cell proliferation during endocardial cushion formation. J Mol Cell Cardiol. 2018 Oct;123:150-158. doi: 10.1016/j.yjmcc.2018.09.001. Epub 2018 Sep 8. PubMed PMID: 30201295; NIHMSID:NIHMS1029902.

Baron RM, Kwon MY, Castano AP, Ghanta S, Riascos-Bernal DF, Lopez-Guzman S, Macias AA, Ith B, Schissel SL, Lederer JA, Reeves R, Yet SF, Layne MD, Liu X, Perrella MA. Frontline Science: Targeted expression of a dominant-negative high mobility group A1 transgene improves outcome in sepsis. J Leukoc Biol. 2018 Oct;104(4):677-689. doi: 10.1002/JLB.4HI0817-333RR. Epub 2018 Jul 5. PubMed PMID: 29975792; PubMed Central PMCID: PMC6431081.

Riascos-Bernal DF, Sibinga NES, Kitsis RN. PDCD5 says no to NO. Proc Natl Acad Sci U S A. 2018 May 1;115(18):4535-4537. doi: 10.1073/pnas.1804491115. Epub 2018 Apr 16. PubMed PMID: 29666279; PubMed Central PMCID: PMC5939121.

Riascos-Bernal DF, Chinnasamy P, Gross JN, Almonte V, Egaña-Gorroño L, Parikh D, Jayakumar S, Guo L, Sibinga NES. Inhibition of Smooth Muscle β-Catenin Hinders Neointima Formation After Vascular Injury. Arterioscler Thromb Vasc Biol. 2017 May;37(5):879-888. doi: 10.1161/ATVBAHA.116.308643. Epub 2017 Mar 16. PubMed PMID: 28302627; PubMed Central PMCID: PMC5408313.

Cao LL*, Riascos-Bernal DF*, Chinnasamy P, Dunaway CM, Hou R, Pujato MA, O'Rourke BP, Miskolci V, Guo L, Hodgson L, Fiser A, Sibinga NE. Control of mitochondrial function and cell growth by the atypical cadherin Fat1. Nature. 2016 Nov 24;539(7630):575-578. doi: 10.1038/nature20170. Epub 2016 Nov 9. PubMed PMID: 27828948; PubMed Central PMCID: PMC5257202. * equal contribution

Riascos-Bernal DF, Chinnasamy P, Cao LL, Dunaway CM, Valenta T, Basler K, Sibinga NE. β-Catenin C-terminal signals suppress p53 and are essential for artery formation. Nat Commun. 2016 Aug 8;7:12389. doi: 10.1038/ncomms12389. PubMed PMID: 27499244; PubMed Central PMCID: PMC4979065.

Chinnasamy P, Lutz SE, Riascos-Bernal DF, Jeganathan V, Casimiro I, Brosnan CF, Sibinga NE. Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion. Mol Med. 2015 Jan 6;21:233-41. doi: 10.2119/molmed.2014.00264. PubMed PMID: 25569805; PubMed Central PMCID: PMC4503655.

Bruder-Nascimento T, Chinnasamy P, Riascos-Bernal DF, Cau SB, Callera GE, Touyz RM, Tostes RC, Sibinga NE. Angiotensin II induces Fat1 expression/activation and vascular smooth muscle cell migration via Nox1-dependent reactive oxygen species generation. J Mol Cell Cardiol. 2014 Jan;66:18-26. doi: 10.1016/j.yjmcc.2013.10.013. PubMed PMID: 24445059; PubMed Central PMCID: PMC3943818.

Baron RM, Lopez-Guzman S, Riascos DF, Macias AA, Layne MD, Cheng G, Harris C, Chung SW, Reeves R, von Andrian UH, Perrella MA. Distamycin A inhibits HMGA1-binding to the P-selectin promoter and attenuates lung and liver inflammation during murine endotoxemia. PLoS One. 2010 May 14;5(5):e10656. doi: 10.1371/journal.pone.0010656. PubMed PMID: 20498830; PubMed Central PMCID: PMC2871042.

Fredenburgh LE, Liang OD, Macias AA, Polte TR, Liu X, Riascos DF, Chung SW, Schissel SL, Ingber DE, Mitsialis SA, Kourembanas S, Perrella MA. Absence of cyclooxygenase-2 exacerbates hypoxia-induced pulmonary hypertension and enhances contractility of vascular smooth muscle cells. Circulation. 2008 Apr 22;117(16):2114-22. doi: 10.1161/CIRCULATIONAHA.107.716241. Epub 2008 Apr 7. PubMed PMID: 18391113; PubMed Central PMCID: PMC2586933.