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A. LYMPEROPOULOS-CV<br />

<strong>Curriculum</strong> <strong>Vitae</strong><br />

Education/Training:<br />

1) Post Doctoral Research Fellow in Molecular Cardiovascular Biology/Medicine, Thomas<br />

Jefferson University, Philadelphia, PA (09/2004 –07/2009)<br />

2) Ph.D. in Pharmacology, University <strong>of</strong> Patras, Patras, Greece (03/2000 - 02/2004)<br />

3) M.Sc. in “Medicinal Chemistry: Drug Design & Development”, University <strong>of</strong> Patras, Patras,<br />

Greece (10/1998 - 03/2000)<br />

4) B.Sc. in <strong>Pharmacy</strong>, University <strong>of</strong> Patras, Patras, Greece (10/1993 - 07/1998)<br />

Positions/Employment, Memberships and Honors:<br />

August 2009-Present: Assistant Pr<strong>of</strong>essor <strong>of</strong> Pharmacology, Dept. <strong>of</strong> Pharmaceutical Sciences,<br />

<strong>College</strong> <strong>of</strong> <strong>Pharmacy</strong>, <strong>Nova</strong> <strong>Southeastern</strong> University, Davie/Ft. Lauderdale, FL.<br />

Duties: Teaching, Research, Administration.<br />

Research focus: Biology and regulation <strong>of</strong> G-protein coupled receptors (GPCRs), such as<br />

adrenergic receptors and receptors for angiotensin II, in the pathophysiology <strong>of</strong> heart failure<br />

and, more broadly, in the neurohormonal control <strong>of</strong> the circulation. The main goal is discovery<br />

<strong>of</strong> new and innovative drugs for countering the cardio-toxic actions <strong>of</strong> catecholamines and <strong>of</strong><br />

angiotensin II (and also <strong>of</strong> other hormones) in heart failure. Particular focus is given on the role<br />

<strong>of</strong> these receptors in adrenal gland function in relation with the cardiovascular system, thus<br />

providing clues for new treatments for cardiovascular disease. The research utilizes cutting-edge<br />

in vivo gene therapy techniques to manipulate, for therapeutic purposes, various GPCR kinases<br />

(GRKs) and beta-arrestins, proteins that normally desensitize receptors (among other functions)<br />

and are involved in heart failure pathophysiology.<br />

August 2004-July 2009: PostDoctoral Research Fellow, Center for Translational<br />

Medicine, Thomas Jefferson University, Philadelphia, PA.<br />

Mentor: Dr. Walter J. Koch<br />

Research focus: Cardiovascular biology/pharmacology and gene therapy, with a particular<br />

interest in mechanisms <strong>of</strong> adrenergic system regulation in heart failure and in ways <strong>of</strong><br />

manipulating these mechanisms for therapeutic purposes. In particular, novel roles <strong>of</strong> G-protein<br />

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A. LYMPEROPOULOS-CV<br />

coupled receptor kinases and their co-factors, beta-arrestins, in regulation <strong>of</strong> various important<br />

cardiovascular G-protein coupled receptors are investigated.<br />

November 1998-November 2003: Graduate Research Assistant, Department <strong>of</strong><br />

Pharmacology, School <strong>of</strong> Medicine, University <strong>of</strong> Patras, Patras, Greece<br />

Mentor: Dr. Chris S. Flordellis<br />

Doctorate thesis project: Study <strong>of</strong> signal transduction from wild-type and polymorphic<br />

human α 2 -adrenergic receptors.<br />

July 1997-August 1997: Visiting Undergraduate Lab Assistant, Department <strong>of</strong> Cell Biology, John<br />

Innes Centre, Norwich Research Park, England, UK<br />

Mentor: Dr. Liam Dolan<br />

Research objective: Additional training in molecular biology techniques.<br />

November 1997-September 1998: Undergraduate Lab Assistant, Department <strong>of</strong> Molecular<br />

Biology, University <strong>of</strong> Patras Medical School, Patras, Greece<br />

Mentors: Dr. Ioannis Zarkadis, Dr. Georgia Sotiropoulou<br />

Research project: Training in basic molecular biology techniques.<br />

Teaching Experience:<br />

2009-Present: Assistant Pr<strong>of</strong>essor, Teaching undergraduate students <strong>of</strong> the PharmD<br />

Program and postgraduate students <strong>of</strong> the PhD program <strong>of</strong> the <strong>Nova</strong> <strong>Southeastern</strong><br />

University`s <strong>College</strong> <strong>of</strong> <strong>Pharmacy</strong>.<br />

Specifically:<br />

Course Coordinator <strong>of</strong> the elective course “Individualized Pharmacotherapy” <strong>of</strong> the<br />

PharmD Program curriculum and <strong>of</strong> the core course “Applied Pharmacology” <strong>of</strong> the<br />

PhD Program curriculum.<br />

Instructor in core courses “Pharmacodynamics IV & V” <strong>of</strong> the PharmD Program<br />

curriculum and in core course “Molecular and Cellular Pharmacodynamics” <strong>of</strong> the<br />

PhD Program curriculum.<br />

Guest Lecturer in core course “Molecular Medicine & Pharmacogenomics” <strong>of</strong> the<br />

PhD Program curriculum and in elective course “Molecular Medicine” <strong>of</strong> the PharmD<br />

Program curriculum.<br />

2003: Guest Lecturer, Special Topics in Molecular Pharmacology and Biology,<br />

Graduate Courses Program in the “Basic Medical Sciences”, School <strong>of</strong> Medicine,<br />

University <strong>of</strong> Patras, Patras, Greece.<br />

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A. LYMPEROPOULOS-CV<br />

1999: Adjunct instructor, Techniques in Molecular Pharmacology, Department <strong>of</strong><br />

Pharmacology, School <strong>of</strong> Medicine, University <strong>of</strong> Patras, Patras, Greece.<br />

Pr<strong>of</strong>essional Associations:<br />

American Heart Association, Premium Pr<strong>of</strong>essional Member <strong>of</strong> the “Basic Cardiovascular<br />

Sciences (BCVS)” & the “Functional Genomics & Translational Biology” councils, since 2006.<br />

Heart Failure Society <strong>of</strong> America, Full Member at the early career/junior faculty level, since<br />

2007.<br />

American Association for the Advancement <strong>of</strong> Science (AAAS), member since February 2005.<br />

New York Academy <strong>of</strong> Sciences, member since October 2005.<br />

American Association <strong>of</strong> <strong>College</strong>s <strong>of</strong> <strong>Pharmacy</strong> (AACP), member since July 2008.<br />

American Chemical Society, member since April 2007.<br />

Greek Society <strong>of</strong> Pharmacology, member since March 2001.<br />

Greek Association <strong>of</strong> Pharmacists, member since February 2001.<br />

Greek Society <strong>of</strong> Biochemistry and Molecular Biology, member since June 1999.<br />

Honors and Awards:<br />

• November 12, 2011: Elected Fellow <strong>of</strong> the American Heart Association (FAHA) with its<br />

“Council on Basic Cardiovascular Sciences (BCVS)”<br />

• Recipient <strong>of</strong> AHA Scientist Development Grant (SDG) Award (National Center) entitled:<br />

“Role <strong>of</strong> adrenal beta-arrestin-1 in angiotensin II-induced aldosterone production in postinfarct<br />

heart failure” (Award ID: 09SDG2010138), Principal Investigator: A. Lymperopoulos,<br />

PhD, Duration: 07/01/2009-06/30/2014, Gross Annual Funding: $77,000 USD<br />

• 2006 Melvin L. Marcus Young Investigator Award in Cardiovascular Sciences Finalist,<br />

“Adrenal G-protein coupled Receptor Kinase 2 Up-regulation Mediates Sympathetic<br />

Overstimulation in Chronic Heart Failure”, American Heart Association Scientific Sessions<br />

2006, Chicago, IL,12-15 November 2006<br />

• 2010 Cardiovascular Research Award <strong>of</strong> the Council on Basic Cardiovascular Sciences <strong>of</strong><br />

the European Society <strong>of</strong> Cardiology (ESC) Finalist, “Genetic deletion <strong>of</strong> β-arrestin-1<br />

improves function <strong>of</strong> the infarcted heart by reducing cardiac β-adrenergic receptor<br />

desensitization and cardiotoxic neurohormonal overstimulation”, Frontiers in<br />

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A. LYMPEROPOULOS-CV<br />

Cardiovascular Biology Congress <strong>of</strong> the ESC Council on Basic Cardiovascular Sciences, Berlin,<br />

Germany, 16-19 July 2010<br />

• AHA Great Rivers (Formerly: Pennsylvania-Delaware) affiliate Post Doctoral Fellowship<br />

award Recipient (July 2005-June 2007)<br />

• AHA Great Rivers (Formerly: Pennsylvania-Delaware) affiliate Post Doctoral Fellowship<br />

award Recipient (One-year extension <strong>of</strong> above fellowship: July 2007-June 2008).<br />

Application received average priority score <strong>of</strong> 1.2778 (best possible: 1.0) and its percentile<br />

rank was 0.76 (best possible: 0.01)<br />

• 1st best oral presentation award winner at the 3rd Jefferson Postdoctoral Research<br />

symposium, held at Thomas Jefferson University, Philadelphia, PA, USA (24 June 2008)<br />

• 1st best poster presentation award winner at the 1st Jefferson Postdoctoral Research<br />

symposium, held at Thomas Jefferson University, Philadelphia, PA, USA (15 May 2006)<br />

• Research Abstract entitled: “Biased Agonism/Antagonism <strong>of</strong> β-arrestin Activation by the<br />

Angiotensin II Type 1 Receptor: a Study <strong>of</strong> Sartans and Angiotensin II Analogs Using<br />

Aldosterone Turnover as a Readout” selected for special honorary presentation at the<br />

“Best <strong>of</strong> AHA Specialty Conferences Poster Session: BCVS 2010”, November 15, 2010,<br />

2010 AHA Scientific Sessions, Chicago, IL, USA, as being a top-scoring abstract (among the<br />

top 10 percent <strong>of</strong> the accepted abstracts for that meeting)<br />

• Award for top <strong>of</strong> class graduating in the “M.Sc. in Medicinal Chemistry” post-graduate<br />

studies program Recipient, University <strong>of</strong> Patras, Patras, Greece (Class 2000)<br />

• Peer reviewer for the American Heart Association`s (AHA) Basic Cardiovascular Sciences<br />

(BCVS) council, both for scientific research grants submitted to AHA for funding and for<br />

scientific abstracts submitted to AHA Scientific Sessions<br />

• New Investigator Award (NIA) research grant peer reviewer for the American Association<br />

<strong>of</strong> <strong>College</strong>s <strong>of</strong> <strong>Pharmacy</strong> (AACP)<br />

• Research grant peer reviewer for the South African Medical Research Council (MRC)<br />

• Undergraduate student fellowship recipient for participation in the “<strong>Pharmacy</strong> Student<br />

Pr<strong>of</strong>essional Training Program”, funded by the European Union Peripheral Development<br />

Support Framework, Scientific Research and Development Support Program II, 1997-1998<br />

• Graduate student fellowship recipient, European Union Peripheral Development Support<br />

Framework, Scientific Research and Development Support Program II, 1998-2000<br />

• Research fellowship recipient, BIOMED II Program, European Union Research Council,<br />

1998-2001<br />

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A. LYMPEROPOULOS-CV<br />

• NATO/FEBS travel/participation grant award recipient, NATO/FEBS Advanced Study<br />

Institute-International Summer School on «Molecular Mechanisms <strong>of</strong> Signal Transduction»,<br />

Island <strong>of</strong> Spetsai, Greece, 1999<br />

• HFSA Travel grant award recipient for participation at the 12th HFSA Annual Scientific<br />

Meeting, held in Toronto, Ontario, Canada, 21-24 September 2008<br />

• EMBO young scientist travel grant award recipient for participation in the EMBO Practical<br />

Course: “Advanced Techniques in Molecular Medicine”, organized by the Departments <strong>of</strong><br />

Medical Sciences, and <strong>of</strong> Genetics and Pathology, Uppsala University, Uppsala, Sweden,<br />

2002<br />

Scholarly and Editorialist Honors and Activities:<br />

1) Associate Editor <strong>of</strong> “Pharmacology Research & Perspectives”, a peer-reviewed journal<br />

<strong>of</strong> the British Pharmacological Society, & Academic Editor <strong>of</strong> “Medicine”, a peerreviewed<br />

medical journal <strong>of</strong> the esteemed publisher Wolters Kluwer Health.<br />

2) Member <strong>of</strong> the Editorial Boards <strong>of</strong> the following peer-reviewed journals: “International<br />

Journal <strong>of</strong> Hematology Research” (since November 2014); “Heart Health” (since<br />

September 2014); “International Archives <strong>of</strong> Clinical Pharmacology” (since November<br />

2014); “Journal <strong>of</strong> Pharmacology and Pharmacovigilance” (since November 2014);<br />

“Toxicology and Allied Clinical Pharmacology” (since August 2014); “Chronic Diseases-<br />

International” (since August 2014); “Journal <strong>of</strong> Pharmacology & Pharmacogenomics”<br />

(since August 2014); “Journal <strong>of</strong> Addiction and Neuropharmacology” (since May 2014);<br />

“International Journal <strong>of</strong> Biochemistry Research & Review” (since April 2014); “Journal<br />

<strong>of</strong> Clinical Immunology and Immunotherapy” (since March 2014); “Journal <strong>of</strong><br />

Endocrine System and Enzymology” (since August 2014); “Case Reports in Internal<br />

Medicine” (since December 2013); “World Journal <strong>of</strong> Cardiology” (since November<br />

2013); “World Journal <strong>of</strong> Biological Chemistry” (since November 2013); “Journal <strong>of</strong><br />

Geriatric Cardiology” (since December 2013); “Journal <strong>of</strong> Cardiology and Therapy”<br />

(since October 2013); “Austin Journal <strong>of</strong> Pharmacology and Therapeutics” (since<br />

October 2013); “Journal <strong>of</strong> Clinical and Laboratory Investigation Updates” (since June<br />

2013); “Journal <strong>of</strong> Pharmacogenomics and Pharmacoproteomics” (since January 2013);<br />

“American Journal <strong>of</strong> Life Sciences” (since December 2012); “American Journal <strong>of</strong><br />

Cardiovascular Disease” (since March 2011); “Journal <strong>of</strong> Carcinogenesis and<br />

Mutagenesis” (since July 2010); and “International Journal <strong>of</strong> Cancer Studies &<br />

Research (IJCR)” (since May 2012).<br />

3) Scientific manuscript reviewer for the following peer-reviewed journals: “Journal <strong>of</strong><br />

Biological Chemistry”, “British Journal <strong>of</strong> Pharmacology”, “Circulation Research”,<br />

“Pharmacogenomics”, “American Journal <strong>of</strong> Cardiology”, “Hypertension”, “European<br />

Journal <strong>of</strong> Biophysics”, “Scientific Reports”, “Molecular Basis <strong>of</strong> Disease”, “American<br />

Heart Journal”, “International Journal <strong>of</strong> Molecular Sciences”, “Drug Design,<br />

Development and Therapy”.<br />

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A. LYMPEROPOULOS-CV<br />

4) Chapter/book peer-reviewer for the pharmacological textbooks/pharmaceutical<br />

monographs: “Remington: The Science and Practice <strong>of</strong> <strong>Pharmacy</strong>” (22 nd edition, 2012) &<br />

“Remington Education: Pharmaceutics” (Author: Shelley Chambers Fox, scheduled for<br />

publication in 2013), both by publisher: “Pharmaceutical Press”, Philadelphia, PA, USA.<br />

Patents:<br />

1) Provisional patent entitled: “Adrenal GRK2 Activity as a Therapeutic Target for<br />

Heart Failure”, Patent ID: KOC_WAL.001, Inventors: Dr. Lymperopoulos, A.,<br />

and Dr. Koch, W.J. Filed with the “Office <strong>of</strong> Technology Transfer”, Thomas<br />

Jefferson University, Philadelphia, PA, 19107, USA. Granted on 01/12/2007,<br />

present status: active.<br />

2) Provisional patent entitled: “Therapeutic strategies for lowering aldosterone levels<br />

post-myocardial infarction and in heart failure”. U.S. Provisional Patent<br />

Application #61/389,819. Inventors: Dr. Lymperopoulos, A., and Dr. Koch, W.J.<br />

Filed by the “Office <strong>of</strong> Technology Transfer”, <strong>Nova</strong> <strong>Southeastern</strong> University, Fort<br />

Lauderdale, FL 33314, USA, on 10/05/2010.<br />

Peer-reviewed Publications:<br />

1) Bathgate-Siryk, A., Dabul, S., Pandya, K., Walklett, K., Rengo, G., Cannavo, A.,<br />

De Lucia, C., Liccardo, D., Gao, E., Leosco, D., Koch, W.J., Lymperopoulos, A.<br />

Negative Impact <strong>of</strong> β-Arrestin-1 on Post-Myocardial Infarction Heart Failure via<br />

Cardiac and Adrenal-Dependent Neurohormonal Mechanisms. Hypertension. 63:<br />

404-412 (2014).<br />

2) Lymperopoulos, A., Garcia, D., Walklett, K. Pharmacogenetics <strong>of</strong> cardiac<br />

inotropy. Pharmacogenomics 15: 1807-1821 (2014). Review.<br />

3) Drosatos, K., Lymperopoulos, A., Kennel, P.J., Pollak, N., Schulze, P.C.,<br />

Goldberg, I.J. Pathophysiology <strong>of</strong> Sepsis-Related Cardiac Dysfunction: Driven by<br />

Inflammation, Energy Mismanagement, or Both Curr. Heart Fail. Rep. 2014 Dec<br />

5. [Epub ahead <strong>of</strong> print]. Invited Review.<br />

4) Lymperopoulos, A., French, F. Pharmacogenomics <strong>of</strong> heart failure. Methods Mol.<br />

Biol. 1175: 245-257 (2014). Invited Book Chapter.<br />

5) Lymperopoulos, A., Negussie, S. βArrestins in Cardiac G Protein-Coupled<br />

Receptor Signaling and Function: Partners in Crime or "Good Cop, Bad Cop" Int.<br />

J. Mol. Sci. 14: 24726-24741 (2013). Review.<br />

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A. LYMPEROPOULOS-CV<br />

6) Salazar, N.C., Vallejos, X., Siryk, A., Rengo, G., Cannavo, A., Liccardo, D., De Lucia, C., Gao,<br />

E., Leosco, D., Koch, W.J., Lymperopoulos, A. GRK2 blockade with betaARKct is essential<br />

for cardiac beta2-adrenergic receptor signaling towards increased contractility. Cell<br />

Commun. Signal. 11: 64 (2013)<br />

7) Lymperopoulos, A., Rengo, G., Koch, W.J. Adrenergic Nervous System in Heart Failure:<br />

Pathophysiology and Therapy. Circ. Res. 113: 739-753 (2013). Invited Review.<br />

8) Siryk-Bathgate, A., Dabul, S., Lymperopoulos, A. Current and future G protein-coupled<br />

receptor signaling targets for heart failure therapy. Drug Des. Devel. Ther. 7: 1209-1222<br />

(2013). Invited Review.<br />

9) Lymperopoulos, A., Bathgate, A. Arrestins in the cardiovascular system. Prog. Mol. Biol.<br />

Transl. Sci. 118: 297-334 (2013). Invited Book Chapter.<br />

10) Lymperopoulos, A., Negussie, S., Walklett, K. Research Highlights: Adrenergic receptor<br />

pharmacogenetics in heart failure. Pharmacogenomics. 14: 1545-1549 (2013). Invited<br />

“Research Highlights” article.<br />

11) Lymperopoulos, A. Physiology and pharmacology <strong>of</strong> the cardiovascular adrenergic system.<br />

Front. Physiol. 4: 240 (2013). Invited Review.<br />

12) Lymperopoulos, A., Bathgate, A. Pharmacogenomics <strong>of</strong> the heptahelical receptor<br />

regulators G-protein-coupled receptor kinases and arrestins: the known and the unknown.<br />

Pharmacogenomics 13: 323-341 (2012). Review.<br />

13) Lymperopoulos, A. Ischemic Emergency: Endothelial Cells Have Their Own "Adrenaline<br />

Shot" at Hand. Hypertension 60: 12-14 (2012). Invited editorial commentary.<br />

14) Rengo, G., Lymperopoulos, A., Zincarelli, C., Femminella, G.D., Liccardo, D., Pagano, G., de<br />

Lucia, C., Cannavo, A., Gargiulo, P., Ferrara, N., Perrone Filardi, P., Koch, W.J., Leosco, D.<br />

Blockade <strong>of</strong> β-adrenoceptors restores the GRK2-mediated adrenal α(2) -adrenoceptorcatecholamine<br />

production axis in heart failure. Br. J. Pharmacol. 166: 2430-2440 (2012)<br />

15) Rengo, G., Zincarelli, C., Femminella, G.D., Liccardo, D., Pagano, G., de Lucia, C., Altobelli,<br />

G.G., Cimini, V., Ruggiero, D., Perrone-Filardi, P., Gao, E., Ferrara, N., Lymperopoulos, A.,<br />

Koch, W.J., Leosco, D. Myocardial β(2)-adrenergic receptor gene delivery promotes<br />

coordinated cardiac adaptive remodeling and angiogenesis in heart failure. Br. J.<br />

Pharmacol. 166: 2348-2361 (2012)<br />

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A. LYMPEROPOULOS-CV<br />

16) Ansari, R.A., Rizvi, S.A., Husain, K., Lymperopoulos, A., Berndt, W.O. Effect <strong>of</strong> sulfhydryl<br />

modification on rat kidney basolateral plasma membrane transport function. Bull. Environ.<br />

Contam. Toxicol. 89: 699-703 (2012)<br />

17) Rengo, G., Perrone-Filardi, P., Femminella, G.D., Liccardo, D., Zincarelli, C., de Lucia, C.,<br />

Pagano, G., Marsico, F., Lymperopoulos, A., Leosco, D. Targeting the β-Adrenergic<br />

Receptor System Through G-Protein-Coupled Receptor Kinase 2: A New Paradigm for<br />

Therapy and Prognostic Evaluation in Heart Failure: From Bench to Bedside. Circ. Heart<br />

Fail. 5: 385-391 (2012). Review.<br />

18) Lymperopoulos, A. Beta-arrestin Biased Agonism/Antagonism at Cardiovascular Seven<br />

Transmembrane- spanning Receptors. Curr. Pharm. Des. 18: 192-198 (2012). Invited<br />

review.<br />

19) Lymperopoulos, A., Rengo, G., Koch, W.J. GRK2 Inhibition in Heart Failure: Something Old,<br />

Something New. Curr. Pharm. Des. 18: 186-191 (2012). Invited review.<br />

20) Lymperopoulos, A., Rengo, G., Zincarelli, C., Kim, J., Koch, W.J. Adrenal β−arrestin 1<br />

inhibition in vivo attenuates post-myocardial infarction progression to heart failure and<br />

adverse remodeling via reduction <strong>of</strong> circulating aldosterone levels. J. Am. Coll. Cardiol. 57:<br />

356-365 (2011)<br />

21) Lymperopoulos, A. GRK2 and β-arrestins in cardiovascular disease: something old,<br />

something new. Am. J. Cardiovasc. Dis. 1: 126-137 (2011). Invited review.<br />

22) Harvey, A.N., Nguyen, K., Lymperopoulos, A. GRK2 and Beta-Arrestins in Cardiovascular<br />

Disease: Established and Emerging Possibilities for Therapeutic Targeting. Curr. Mol.<br />

Pharmacol. 6: 317-326 (2013). Review.<br />

23) Nguyen, K., Kassimatis, T., Lymperopoulos, A. Impaired desensitization <strong>of</strong> a human<br />

polymorphic alpha2B-adrenergic receptor variant enhances its sympatho-inhibitory<br />

activity in chromaffin cells. Cell Commun. Signal. 9: 5 (2011)<br />

24) Jasmin, J.F., Rengo, G., Lymperopoulos, A., Gupta, R., Eaton, G.J., Quann, K., Gonzales,<br />

D.M., Mercier, I., Koch, W.J., Lisanti, M.P. Caveolin-1 Deficiency Exacerbates Cardiac<br />

Dysfunction and Reduces Survival in Mice with Myocardial Infarction. Am. J. Physiol. Heart<br />

Circ. Physiol. 300: H1274-H1281 (2011)<br />

25) Drosatos, K., Bharadwaj. K.G., Lymperopoulos, A., Ikeda, S., Khan, R., Hu, Y., Agarwal, R.,<br />

Yu, S., Jiang, H., Steinberg, S.F., Blaner, W.S., Koch, W.J., Goldberg, I.J. Cardiomyocyte<br />

lipids impair {beta}-adrenergic receptor function via PKC activation. Am. J. Physiol.<br />

Endocrinol. Metab. 300: E489-E499 (2011)<br />

26) Rengo, G., Lymperopoulos, A., Leosco, D., Koch, W.J. GRK2 as a novel gene therapy target<br />

in heart failure. J. Mol. Cell. Cardiol. 50: 785-792 (2011). Review.<br />

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27) Lymperopoulos, A., Rengo, G., Gao, E., Ebert, S.N., Dorn, G.W. 2nd, Koch, W.J. Reduction<br />

<strong>of</strong> sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure<br />

progression and improves cardiac function after myocardial infarction. J. Biol. Chem. 285:<br />

16378-16386 (2010)<br />

28) Rengo, G., Leosco, D., Zincarelli, C., Marchese, M., Corbi, G., Liccardo, D., Filippelli, A.,<br />

Ferrara, N., Lisanti, M.P., Koch, W.J., Lymperopoulos, A. Adrenal GRK2 lowering is an<br />

underlying mechanism for the beneficial sympathetic effects <strong>of</strong> exercise training in heart<br />

failure. Am. J. Physiol. Heart Circ. Physiol. 298: H2032-H2038 (2010)<br />

29) Kassimatis, T.I., Nomikos, A., Giannopoulou, I., Lymperopoulos, A., Moutzouris, D.A.,<br />

Varakis, I., Nakopoulou, L. Transcription factor Sp1 expression is upregulated in human<br />

glomerulonephritis: correlation with pSmad2/3 and p300 expression and renal injury. Ren.<br />

Fail. 32: 243-253 (2010)<br />

30) Lymperopoulos, A., Rengo, G., Zincarelli, C., Kim, J., Soltys, S., Koch W.J. An adrenal β-<br />

arrestin 1-mediated signaling pathway underlies angiotensin II-induced aldosterone<br />

production in vitro and in vivo. Proc. Natl. Acad. Sci. USA 106: 5825-5830 (2009)<br />

31) Rengo, G., Lymperopoulos, A., Koch W.J. Future G-protein coupled receptor targets for<br />

treatment <strong>of</strong> heart failure. Curr. Treat. Options Cardiovasc. Med. 11: 328-338 (2009).<br />

Review.<br />

32) Rengo, G., Lymperopoulos, A., Zincarelli, C., Donniacuo, M., Soltys, S., Rabinowitz, J.E.,<br />

Koch W.J. Myocardial adeno-associated virus serotype 6-betaARKct gene therapy<br />

improves cardiac function and normalizes the neurohormonal axis in chronic heart failure.<br />

Circulation 119: 89-98 (2009)<br />

33) Lymperopoulos, A., Rengo, G., Zincarelli, C., Soltys, S., Koch W.J. Modulation <strong>of</strong> Adrenal<br />

Catecholamine Secretion by In Vivo Gene Transfer and Manipulation <strong>of</strong> G Protein-Coupled<br />

Receptor Kinase-2 Activity. Mol. Ther. 16: 302-307 (2008)<br />

34) Lymperopoulos, A., Rengo, G., Koch, W.J. Adrenal adrenoceptors in heart failure: Finetuning<br />

cardiac stimulation. Tr. Mol. Med. 13: 503-511 (2007). Invited review, featured<br />

cover article.<br />

35) Lymperopoulos, A., Rengo, G., Funakoshi, H., Eckhart, A.D., Koch, W.J. Adrenal GRK2<br />

upregulation mediates sympathetic overdrive in heart failure. Nat. Med. 13: 315-323<br />

(2007). Important Note: This journal (“Nature Medicine”) is the top primary research<br />

journal in Medicine (Research and Experimental), with an “Impact Factor” <strong>of</strong> 27.553 (2008<br />

ISI Journal Citation Reports).<br />

36) Leosco, D., Rengo, G., Iaccarino, G., Filippelli, A., Lymperopoulos, A., Zincarelli, C.,<br />

Fortunato, F., Golino, L., Marchese, M., Esposito, G., Rapacciuolo, A., Rinaldi, B., Ferrara,<br />

N., Koch, W.J., Rengo, F. Exercise training and beta-blocker treatment ameliorate agedependent<br />

impairment <strong>of</strong> beta-adrenergic receptor signaling and enhance cardiac<br />

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A. LYMPEROPOULOS-CV<br />

responsiveness to adrenergic stimulation. Am. J. Physiol. Heart Circ. Physiol. 293: H1596-<br />

H1603 (2007)<br />

37) Flordellis, C., Papathanasopoulos, P., Lymperopoulos, A., Matsoukas, J., Paris, H. Emerging<br />

therapeutic approaches multi-targeting receptor tyrosine kinases and g protein-coupled<br />

receptors in cardiovascular disease. Cardiovasc. Hematol. Agents Med. Chem. 5: 133-145<br />

(2007). Review<br />

38) Karkoulias, G., Mastrogianni, O., Ilias, I., Lymperopoulos, A., Taraviras, S., Tsopanoglou, N.,<br />

Sitaras, N., Flordellis, C.S. Alpha 2-adrenergic receptors decrease DNA replication and cell<br />

proliferation and induce neurite outgrowth in transfected rat pheochromocytoma cells.<br />

Ann. N. Y. Acad. Sci. 1088: 335-345 (2006)<br />

39) Lymperopoulos, A., Karkoulias, G., Koch, W.J., Flordellis, C.S. alpha(2)-Adrenergic receptor<br />

subtype-specific activation <strong>of</strong> NF-kappaB in PC12 cells. Neurosci. Lett. 402: 210-215 (2006)<br />

40) Manolis, A.S., Patsouras, N., Ilias, I., Constantakopoulos, J., Pyriohou, A., Lymperopoulos,<br />

A., Spathas, D.H., Flordellis C.S. Lack <strong>of</strong> association between alpha2B-adrenergic receptor<br />

polymorphism and risk <strong>of</strong> restenosis following coronary angioplasty and stent<br />

implantation--preliminary report. Clin. Chem. Lab. Med. 44: 807-812 (2006)<br />

41) Karkoulias, G., Mastrogianni, O., Lymperopoulos, A., Paris, H., Flordellis, C. alpha(2)-<br />

Adrenergic receptors activate MAPK and Akt through a pathway involving arachidonic acid<br />

metabolism by cytochrome P450-dependent epoxygenase, matrix metalloproteinase<br />

activation and subtype-specific transactivation <strong>of</strong> EGFR. Cell. Signal. 18: 729-739 (2006)<br />

42) Flordellis, C., Paris, H., Karabinis, A., Lymperopoulos, A. Pharmacogenomics <strong>of</strong><br />

adrenoceptors. Pharmacogenomics 5: 803-817 (2004). Review<br />

43) Taraviras, S., Olli-Lahdesmaki, T., Lymperopoulos, A., Charitonidou, D., Mavroidis, E.,<br />

Kallio, J., Scheinin, M., Flordellis, C. α 2 -adrenergic receptor subtypes regulate neuronal<br />

differentiation <strong>of</strong> transfected PC12 cells through MAPK activation. Eur. J. Cell Biol. 81: 363-<br />

374 (2002)<br />

44) Schaak, S., Cayla, C., Lymperopoulos, A., Flordellis, C., Cussac, D., Denis, C., and Paris, H.<br />

Transcriptional down-regulation <strong>of</strong> the human α 2C -adrenergic receptor by cAMP. Mol.<br />

Pharmacol. 58: 821-827 (2000)<br />

Textbooks-Book Chapters:<br />

1) Lymperopoulos, A., and French, F. Pharmacogenomics <strong>of</strong> Heart Failure. In Qing<br />

Yan (Editor): Pharmacogenomics in Drug Discovery and Development, 2 nd<br />

Edition, Methods in Molecular Biology-Springer Protocols, UK: Humana Press,<br />

2014, pp. 245-257 (2014)<br />

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A. LYMPEROPOULOS-CV<br />

2) Lymperopoulos, A., and Bathgate, A. Arrestins in the Cardiovascular System. In<br />

Louis M. Luttrell, editors: The Molecular Biology <strong>of</strong> Arrestins, Vol. 118, PMBTS,<br />

UK: Academic Press, 2013, pp. 297-334 (2013)<br />

3) Lymperopoulos, A., Rengo, G., Gao, E., Ebert, S.N., Dorn, G.W., and Koch,<br />

W.J. Adrenal-specific G protein-coupled receptor kinase (GRK)-2 deficiency<br />

reduces circulating catecholamine levels and improves cardiac function after<br />

myocardial infarction. In L. Eiden (Editor): Catecholamine Research in the 21st<br />

Century: Abstracts and Graphical Abstracts, 10th International Catecholamine<br />

Symposium 2012, Oxford, UK: Elsevier, 2013, p. 224, Theme H: Catecholamines<br />

in the Periphery (2013)<br />

4) Lymperopoulos, A., and Koch, W.J. Autonomic Pharmacology. In<br />

Pharmacology and Therapeutics: Principles to Practice (1st edn) (Waldman, S.A.<br />

and Terzic, A., eds), Part 1: Principles, Section 3: Systems pharmacology,<br />

Chapter 9: Autonomic Pharmacology, pp. 115-139, Saunders/Elsevier, ISBN: 978-<br />

1-4160-3291-5, Language: English (2009)<br />

5) Lymperopoulos, A., Pairas, G., Scheinin, M., and Flordellis, C. Decreased GRKmediated<br />

Phosphorylation <strong>of</strong> a Polymorphic α 2B -adrenergic Receptor in PC12<br />

Cells. 3rd HELLENIC FORUM ON BIOACTIVE PEPTIDES, P.A.<br />

Cordopatis, E. Manessi-Zoupa and G. Pairas (Eds.), TYPORAMA, pp. 259-273<br />

(2003)<br />

6) Manolis, A.S., Lymperopoulos, A., Bouga, E.A., Scheinin, M., and Flordellis,<br />

C.S. Significance <strong>of</strong> G-protein –coupled receptor polymorphisms: The case <strong>of</strong> α 2 -<br />

adrenergic receptor. Drug Discovery and Design: Medical Aspects, J.Matscoukas<br />

and T. Mavromoustakos (Eds.), IOS Press, Vol. 55: 299-304 (2002)<br />

Published Abstracts:<br />

1) Lymperopoulos, A., Rengo, G., Koch, W.J. Regulation <strong>of</strong> aldosterone levels by adrenal<br />

βarrestin-1 as a new molecular target in heart failure. J. Heart Disease, Vol. 8, Nr. 1, July<br />

2011, p. 117, Oral Presentation Abstract #467, 16 th World Congress on Heart Disease,<br />

Vancouver, BC, Canada, 23-26 July 2011<br />

2) Lymperopoulos, A., Rengo, G., Magafa, V., Cordopatis, P., Koch, W.J. Biased<br />

Agonism/Antagonism <strong>of</strong> Sartans and Angiotensin II Analogs for Angiotensin II<br />

Type 1 Receptor-Induced, β-Arrestin-Dependent Aldosterone Production in Heart<br />

Failure. Circ. Suppl. II, Vol. 122, Oral Presentation Abstract #10263, 2010 AHA<br />

Scientific Sessions, Chicago, IL, USA, 13-17 November 2010<br />

3) Jasmin, J.F., Rengo, G., Lymperopoulos, A., Gupta, R., Eaton, G., Quann, K.,<br />

Gonzales, D., Mercier, I., Koch, W.J., Lisanti, M.P. Caveolin-1 Deficiency<br />

Exacerbates Cardiac Dysfunction and Reduces Survival in Mice with Myocardial<br />

Infarction. Circ. Suppl. II, Vol. 122, Poster Presentation Abstract #14567, 2010<br />

AHA Scientific Sessions, Chicago, IL, USA, 13-17 November 2010<br />

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4) Lymperopoulos, A., Rengo, G., Magafa, V., Cordopatis, P., Koch, W.J. Biased<br />

Agonism/Antagonism <strong>of</strong> β-Arrestin activation by the Angiotensin II Type 1<br />

Receptor: A Study <strong>of</strong> Sartans and Angiotensin II Analogs Using Aldosterone<br />

Turnover as a Readout. J. Card. Fail. Suppl. 1 August 2010, Vol. 16, No 8, S30-<br />

S31, Abstract #088, 14th HFSA Annual Scientific Meeting, San Diego, CA, USA,<br />

12-15 September 2010<br />

5) Lymperopoulos, A., Rengo, G., Koch, W.J. Biased agonism/antagonism <strong>of</strong> β-<br />

arrestin activation by the angiotensin II type 1 receptor: a study <strong>of</strong> sartans and<br />

angiotensin II analogs using aldosterone turnover as a readout. Eur. Heart J.<br />

(2010) 31 (Suppl. 1): 1-296, p. 75, Abstract #P593, ESC Congress 2010,<br />

Stockholm, Sweden, 28 August-1 September 2010<br />

6) Lymperopoulos, A., Rengo, G., Gao, E., Zincarelli, C., Koch, W.J. Genetic<br />

deletion <strong>of</strong> β-arrestin-1 improves function <strong>of</strong> the infarcted heart by reducing<br />

cardiac β-adrenergic receptor desensitization and cardiotoxic neurohormonal<br />

overstimulation. Cardiovasc. Res., Vol. 87, Suppl. 1, S92-S93, Oral Presentation<br />

Abstract #302, Frontiers in Cardiovascular Biology Congress <strong>of</strong> the ESC Council<br />

on Basic Cardiovascular Sciences, Berlin, Germany, 16-19 July 2010<br />

7) Lymperopoulos, A., Rengo, G., Gao, E., Zincarelli, C., Koch, W.J. Genetic<br />

deletion <strong>of</strong> β-arrestin-1 improves function <strong>of</strong> the infarcted heart by reducing<br />

cardiac β-adrenergic receptor desensitization and cardiotoxic neurohormonal<br />

overstimulation. Circ. Suppl. II, Vol. 120, S1177, Oral Presentation Abstract<br />

#5935, 2009 AHA Scientific Sessions, Orlando, FL, USA, 14-18 November 2009<br />

8) Rengo, G., Lymperopoulos, A., Zincarelli, C., Femminella, G., Liccardo, D.,<br />

Corbi, G., Fillipelli, A., Ferrara, N., Koch, W.J., Leosco, D. Beta-adrenergic<br />

blockade reduces sympathetic overactivation in heart failure and restores adrenal<br />

GRK2-alpha 2 -adrenergic receptor-catecholamine production axis. Circ. Suppl. II,<br />

Vol. 120, S801, Oral Presentation Abstract #3394, 2009 AHA Scientific Sessions,<br />

Orlando, FL, USA, 14-18 November 2009<br />

9) Zincarelli, C., Rengo, G., Golino, L., Lymperopoulos, A., Altobelli, G., Cimini,<br />

V., Marchese, M., De Lucia, C., Koch, W.J., Leosco, D. Cardiac β 1 -adrenergic<br />

receptor blockade promotes angiogenesis in the post-ischemic failing heart via<br />

activation <strong>of</strong> VEGF- and Akt-dependent signaling pathways. Circ. Suppl. II, Vol.<br />

120, S1053-S1054, Poster Presentation Abstract #5118, 2009 AHA Scientific<br />

Sessions, Orlando, FL, USA, 14-18 November 2009<br />

10) Lymperopoulos, A., Rengo, G., Gao, E., Koch, W.J. Genetic Deletion <strong>of</strong> β-<br />

arrestin-1 improves function <strong>of</strong> the infarcted heart by reducing cardiac β-<br />

adrenergic receptor desensitization and cardiotoxic neurohormonal<br />

overstimulation. J. Card. Fail. Suppl. 1 2009, Vol. 15, No 6, S7, Abstract #016,<br />

13th HFSA Annual Scientific Meeting, August 2009<br />

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A. LYMPEROPOULOS-CV<br />

11) Lymperopoulos, A., Rengo, G., Zincarelli, C., Kim, J., Soltys, S., Koch, W.J. A<br />

Crucial Role for Adrenal β−Αrrestin 1 in Angiotensin II-Dependent Aldosterone<br />

Production During Post-Myocardial Infarction Heart Failure Progression. Poster<br />

presentation #P106, Basic Cardiovascular Sciences Conference 2009-Molecular<br />

Mechanisms <strong>of</strong> Cardiovascular Disease, Lake Las Vegas, NV, USA (July 20-23,<br />

2009)<br />

12) Rengo, G., Lymperopoulos, A., Zincarelli, C., Marchese, M., Rengo, A.,<br />

Avallone, A., Filippelli, A., Ferrara, N., Koch, W.J., Leosco, D. Restoration <strong>of</strong><br />

adrenal GRK2-mediated catecholamine production is an underlying mechanism<br />

for reduction <strong>of</strong> sympathetic activation by exercise training in heart failure. Eur.<br />

Heart J. 2009; Vol. 30 (Abstract Supplement): 132, European Society <strong>of</strong><br />

Cardiology Congress 2009, Barcelona, Spain (29 August-2 September 2009)<br />

13) Lymperopoulos, A., Rengo, G., Gao, E., Moraca, S.R., Ebert, S.N., Dorn, G.W.<br />

2nd, Koch, W.J. Adrenal-Targeted GRK2 Gene Deletion Ameliorates<br />

Sympathetic Overstimulation and Improves Function <strong>of</strong> the Failing Heart. Circ.<br />

Suppl. II, Vol. 118, No 18, S360-S361, Abstract #1629, October 28, 2008<br />

14) Lymperopoulos, A., Rengo, G., Gao, E., Moraca, S.R., Ebert, S.N., Dorn, G.W.<br />

2nd, Koch, W.J. Adrenal-Targeted GRK2 Gene Deletion Ameliorates<br />

Sympathetic Overstimulation and Improves Function <strong>of</strong> the Failing Heart. J. Card.<br />

Fail. Suppl. 2008, Vol. 14, No 6, S34, Abstract #102, 12th HFSA Annual<br />

Scientific Meeting, August 2008<br />

15) Rengo, G., Lymperopoulos, A., Zincarelli, C., Donniacuo, M., Soltys, S.,<br />

Rabinowitz, J.E., Koch W.J. Long-term AAV6-βARKct Myocardial Gene<br />

Therapy Improves Cardiac Function Via Restoration Of β-Adrenergic Receptor<br />

Signaling and Neurohormonal Status <strong>of</strong> The Failing Heart. Circ. Suppl. II, Vol.<br />

118, No 18, S286, Abstract #339, October 28, 2008<br />

16) Lymperopoulos, A., Rengo, G., Chuprun, J.K., Koch, W.J. Adrenal beta-arrestin<br />

1 mediates angiotensin II-induced aldosterone production in vitro and in vivo.<br />

Circ. Suppl. II, Vol. 116, No 16, II-158, Abstract #815, October 16, 2007<br />

17) Lymperopoulos, A., Rengo, G., Chuprun, J.K., Koch, W.J. Adrenal beta-arrestin<br />

1 mediates physiological production <strong>of</strong> aldosterone in vivo, J. Card. Fail. Suppl.<br />

2007, Vol. 13, No 6, S102, Abstract #097, 11th HFSA Annual Scientific Meeting,<br />

August 2007<br />

18) Rengo, G., Lymperopoulos, A., Zincarelli, C., Soltys, S., Koch W.J. Modulation<br />

<strong>of</strong> Catecholamine Secretion by In Vivo Gene Transfer <strong>of</strong> G Protein-Coupled<br />

Receptor Kinase (GRK) Or A GRK2 Inhibitor Peptide In The Adrenal Gland,<br />

Circ. Suppl. II, Vol. 116, No 16, II-158, Abstract #818, October 16, 2007<br />

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19) Lymperopoulos, A., Funakoshi, H., Shapiro, M., Cohn, H.I., Eckhart, A.D.,<br />

Angelotti, T., Koch, W.J. Adrenal G-protein coupled Receptor Kinase (GRK) 2<br />

activity is a potential novel bio-marker <strong>of</strong> sympathetic outflow in chronic heart<br />

failure, Circ. Suppl. II, Vol. 114, No 18, II-36, Abstract #318, October 31, 2006<br />

20) Lymperopoulos, A., Pleger. S.T., Eckhart, A.D., Koch, W.J. Adrenal G-protein<br />

Coupled Receptor Kinase 2 Up-regulation Mediates Catecholaminergic<br />

Overstimulation <strong>of</strong> the Failing Heart. Circ. Suppl. II, Vol. 112, No 17, II-80,<br />

Abstract #468, October 25, 2005<br />

21) Lymperopoulos, A. The impact <strong>of</strong> GPCR polymorphisms on medicinal<br />

chemistry. Lecture L31, 5th INTERNATIONAL CONFERENCE IN<br />

“MEDICINAL CHEMISTRY: DRUG DISCOVERY AND DESIGN”, Patras,<br />

Greece (2004)<br />

22) Lymperopoulos, A., Pairas, G., Scheinin, M., and Flordellis, C. Impaired<br />

agonist-promoted desensitization <strong>of</strong> a polymorphic α 2B -adrenergic receptor in<br />

PC12 cells. European Journal <strong>of</strong> Drug Metabolism and Pharmacokinetics, Vol.<br />

28, Nr. 1: Page 17 (2003)<br />

23) Lymperopoulos, A., Pandeli, E., Karkoulias, G., Mastroyianni, O., Pyriohou, A.,<br />

and Flordellis, C. Epinephrine Induces the Activation <strong>of</strong> the Transcription Factors<br />

AP-1 and NF-κB in PC12 Cells Transfected with α 2 -Adrenergic Receptors.<br />

Review <strong>of</strong> Clinical Pharmacology and Pharmacokinetics, Greek Edition 2003, 21:<br />

32-33 (2003)<br />

24) Lymperopoulos, A., Taraviras, S., Mastroyianni, O., Stavropoulou, E.,<br />

Kasimatis, T., and Flordellis, C. Phosphatidylinositol-3 Kinase (PI-3K) Mediates<br />

Epinephrine-Induced Survival and Differentiation <strong>of</strong> PC12- α 2 Cells. Review <strong>of</strong><br />

Clinical Pharmacology and Pharmacokinetics, International Edition, 16: 15 (2002)<br />

25) Lymperopoulos, A., Schaak, S., Charitonidou, D., Cayla, C., Denis, C., Paris, H.,<br />

and Flordellis, C. cAMP down-regulates α2C-adrenergic receptor at the<br />

transcriptional level in HepG2 cells. NATO/FEBS Advanced Study Institute-<br />

International Summer School on «Molecular Mechanisms <strong>of</strong> Signal<br />

Transduction», Island <strong>of</strong> Spetsai, Greece. Review <strong>of</strong> Clinical Pharmacology and<br />

Pharmacokinetics, International Edition, 13: 61 (1999)<br />

Research Financial Support:<br />

1) AHA Scientist Development Grant (SDG) Award (National Center) entitled:<br />

“Role <strong>of</strong> adrenal beta-arrestin-1 in angiotensin II-induced aldosterone production<br />

in post-infarct heart failure” (Award ID: 09SDG2010138), PI: Dr. Anastasios<br />

Lymperopoulos, Duration: 07/01/2009-06/30/2014, Gross Annual Funding:<br />

77,000 $<br />

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A. LYMPEROPOULOS-CV<br />

2) AHA Great Rivers (Formerly: Pennsylvania-Delaware) affiliate Post-Doctoral<br />

Research Fellowship, “Role <strong>of</strong> Adrenal GRKs in Regulation <strong>of</strong> Sympathetic<br />

Nervous System Activity in Heart Failure”, July 2005-July 2008, Thomas<br />

Jefferson University, Philadelphia, PA. PI: Dr. Walter J. Koch<br />

3) Co-Investigator, “Adrenal GRKs and Adrenergic Signaling in Heart Failure”,<br />

NIH Research Grant: R01 HL085503-01A1, April 2007-July 2009. PI: Dr. Walter<br />

J. Koch<br />

4) <strong>Nova</strong> <strong>Southeastern</strong> University`s President's Faculty Research & Development<br />

Grant (PFRDG)-FY 2014 (NSU intramural grant) entitled: “Angiotensin receptor<br />

blockers & beta-arrestin-dependent aldosterone production” (Award ID: PFRDG<br />

335320), PI: Dr. Anastasios Lymperopoulos, Duration: 08/01/2013-07/31/2014,<br />

Total Funding: 9,661 $<br />

5) <strong>Nova</strong> <strong>Southeastern</strong> University`s Health Pr<strong>of</strong>essions Division (HPD) Research<br />

Grant (NSU-HPD intramural grant) entitled: “Role <strong>of</strong> beta-arrestin-1 in<br />

aldosterone production from adrenocortical cells” (Award ID: 335797-RX-<br />

Lymperopoulos-BetaArrestin1), PI: Dr. Anastasios Lymperopoulos, Duration:<br />

10/01/2011-09/30/2012, Total Funding: 5,000 $<br />

6) Co-Investigator, “Study <strong>of</strong> Signal Transduction <strong>of</strong> cloned α 2 -adrenergic receptors<br />

in homologous and heterologous cell lines”. BIOMED II Program, European<br />

Union Research Council, 1998-2001. PI: Dr. Chris S. Flordellis<br />

15

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