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Vascular Medicine Institute
University of Pittsburgh
BST E1240
200 Lothrop Street
Pittsburgh, PA 15261
Phone: 412-383-5853
Fax: 412-648-5980

M. Eugenia Cifuentes-Pagano, PhD

 

Eugenia Cifuentes-Pagano

 

Eugenia Cifuentes-Pagano, PhD

Instructor, Department of Pharmacology and Chemical Biology

Co-Director, EPR-ROS Core

E1228 BST
200 Lothrop Street
Pittsburgh, PA 15261

Phone: 412-648-2610
Email: mec110@pitt.edu


Pagano Lab

   

Bio

After obtaining a BS in Biology and a MS in Cell Biology at the University of Chile, Dr. Cifuentes-Pagano move to US to work with Drs. Ikemoto and Hidalgo, at the Boston Biomedical Research Institute, in a project  involving the role of sarcoplasmic reticulum in the excitation-contraction coupling in muscle. Dr. Cifuentes-Pagano obtained her Ph.D. in Physiology and Biophysics at the State University on New York at Stony Brook studying the catalytic and membrane binding properties of phosphoinositide-specific phospholipase C-delta 1 (PLC-d1) . After 10 years at Henry Ford Hospital in Michigan, first as a Posdoctoral Fellow at the Urology Department and later as a Research Instructor at the Hypertension and Vascular Research Division, Dr. Cifuentes-Pagano moved to Pittsburgh where she assumed the position of Research Instructor at the Pharmacology & Chemical Biology Department at the University of Pittsburgh School of Medicine.

Research Interests

Dr. Cifuentes-Pagano’s research interests focus on the understanding of the molecular mechanisms of action of novel NADPH oxidase isoforms and their regulation in the vasculature.  The phagocyte NADPH oxidase (or respiratory burst oxidase) is a well-characterized reactive oxygen species (ROS)-generating system that catalyzes the one-electron reduction of oxygen to O2-, the precursor to a variety of other reactive oxygen species.  The NADPH oxidase paradigm is a multi-subunit enzyme complex that includes two membrane-spanning subunits, p22-phox and nox2 , and three cytoplasmic subunits, p40-phox, p47-phox and p67-phox.  Our laboratory was the first to discover a nox2-based oxidase in the vasculature and to develop specific inhibitors targeting this robust source of ROS.   Since that initial discovery, various isoforms of NADPH oxidase have been described which differ from the nox2 system in unique modifications of  their nox-subunit amino acid sequence as well as the cytoplasmic components that they require.  Besides their structural differences, the various isoforms present differential tissue and cellular distribution.  The multi-level complexity of this family of proteins provides an opportunity to develop new tools to dissect the role of each of the isoforms in vascular function and pathology.

Concentration-response analyses of compounds 11g (A) and 11h (B) for inhibition of Nox1, 2, 4 and 5 in whole cells.

   

In silico analysis reveals interaction preference for the super-SH3 binding groove located within the p47phox. Upper left pannel represents crystalized p47phox (1OV3) with interacting p22phox PRR peptide (PPPSNPPPRPP) which was used for subsequent interaction analysis.   

 

 

Key Publications

Pagano PJ, Clark JK, Cifuentes-Pagano ME, Clark SM, Callis GM, Quinn MT.  Localization of a constitutively active, phagocyte- like NADPH oxidase in rabbit aortic adventitia: enhancement by angiotensin II. Proc. Natl. Acad. Sci. U. S. A. 94: 14483-14488, 1997.

Cifuentes ME, Rey FE, Carretero  OA, Pagano PJ. Upregulation of p67(phox) and gp91(phox) in aortas from angiotensin II-infused miceAm. J. Physiol. Heart Circ. Physiol. 279: H2234-H2240, 2000.

Rey FE, Cifuentes ME, Kiarash A, Quinn MT, Pagano PJ. Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O2- and systolic blood pressure in mice. Circ Res. 2001 89: 408-414, 2001.

Cifuentes ME, Pagano PJ. c-Src and smooth muscle NAD(P)H oxidase: assembling a path to hypertrophy. Arterioscler. Thromb. Vasc. Biol. 23: 919-921, 2003.

Cifuentes ME, and Pagano PJ.  Targeting reactive oxygen species in hypertension. Curr. Opin. Nephrol. Hypertens. 15: 179-186, 2006.

Haurani MJ, Cifuentes ME, Shepard AD, Pagano PJ.  Nox4 Oxidase Overexpression Specifically Decreases Endogenous Nox4 mRNA and Inhibits Angiotensin II-Induced Adventitial Myofibroblast Migration.   Hypertension 52(1):143-9, 2008.

Ardanaz N, Yang XP, Cifuentes ME, Haurani MJ, Jackson, Liao TD, Carretero OA and Pagano PJ.  Lack of glutathione peroxidase 1 accelerates cardiac-specific hypertrophy and dysfunction in angiotensin II hypertension.  Hypertension 55:116-123, 2010.

Csányi G (1), Cifuentes-Pagano E (1),  Al Ghouleh I, Ranayhossaini DJ, Egaña L, Lopes LR, Jackson HM, Kelley EE, Pagano PJ. Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2.  Free Radical Biology and Medicine. (2011)  Apr 17. [Epub ahead of print]  (1 These authors contributed equally to this work.)

Al Ghouleh I, Khoo NKH, Knaus UG, Griendling KK, Touyz RM, Thannickal VJ, Barchowsky A, Nauseef WM, Kelley EE, Bauer PM, Darley-Usmar V, Shiva S, Cifuentes-Pagano E, Freeman BA, Gladwin MT,  & Pagano PJ. Oxidases and peroxidases in cardiovascular and Lung Disease: New concepts in reactive oxygen species signaling. Free Radical Biology and Medicine (2011), doi: 10.1016/j.freeradbiomed.2011.06.011

Cifuentes-Pagano E, Csanyi G, Pagano PJ. NADPH oxidase inhibitors: a decade of discovery from Nox2ds to HTS. Cell Mol Life Sci. 2012; 69(14):2315-25. PubMed PMID: 22585059, PMCID: PMC4372123

Grubisha MJ, Cifuentes ME, Hammes SR, Defranco DB. A local paracrine and endocrine network involving TGFβ, Cox-2, ROS, and estrogen receptor β influences reactive stromal cell regulation of prostate cancer cell motility. Mol Endocrinol. 2012 Jun;26(6):940-54. Erratum in: Mol Endocrinol. 2014 Feb;28(2):275. PubMed PMID: 22593181, PMCID: PMC3355541

Cifuentes-Pagano E, Meijles DN, Pagano PJ. The quest for selective nox inhibitors and therapeutics: challenges, triumphs and pitfalls. Antioxid Redox Signal. 2014 Jun 10;20(17):2741-54. PubMed PMID: 24070014, PMCID: PMC4026400

Cifuentes-Pagano E, Saha J, Csányi G, Ghouleh IA, Sahoo S, Rodríguez A, Wipf P, Pagano PJ, Skoda EM. Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors. Med Chem Comm. 2013; 4(7):1085-1092.PubMed PMID: 24466406, PMCID: PMC3897123

Pubmed link