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    Nicole Purcell

    TitleAssociate Adjunct Professor
    SchoolUniversity of California, San Diego
    DepartmentPharmacology
    Address9500 Gilman Drive #0636
    CA La Jolla 92093
    Phone858-822-5696
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      Collapse Biography 
      Collapse Education and Training
      Susquehanna University, PABS1996Biochemistry
      University of Alabama Birmingham , ALPh.D.2001Molecular and Cellular Pathology

      Collapse Overview 
      Collapse Overview
      Cardiovascular disease and development of heart failure are amongst the primary causes of death in the United States and worldwide. We have found that a newly discovered phosphatase, PHLPP, negatively regulates Akt activity and survival in the heart. My research focus is to further understand through removal of PHLPP, its isoform specificity for Akt and target substrates following cardiac injury and regeneration and determine the potential for PHLPP as a target for therapeutic strategies to improve cardiac function. Studies in this area use in vitro cell culture systems (i.e. NRVM , AMVM and cardiac progenitor cells) and in vivo transgenic and knockout mouse models for phenotypic and morphometric analysis of cardiac hypertrophy and failure at baseline as well as after cardiac interventions (i.e. TAC, MI and I/R). A second area of interest in my laboratory involves investigating the role of PHLPP in astrocyte signaling and cerebral ischemia. In the course of a stroke, the brain is highly affected by the loss of oxygen, glucose, and other nutrients, which in turn, initiates intracellular signaling cascades that are both deleterious and beneficial to the brain. This project uses PHLPP gene-targeted mice and primary astrocytes to investigate novel mechanisms associated with signaling pathways leading to cell death and in particular the hypothesis that astrocyte viability is important to neuronal survival during stroke.


      Collapse Research 
      Collapse Research Activities and Funding
      Role of PHLPP in the Heart
      NIH/NHLBI R01HL114949Feb 1, 2014 - Jan 31, 2019
      Role: Principal Investigator
      MAPK signaling in cardiac hypertrophy and apoptosis
      NIH/NHLBI F32HL071427Aug 12, 2002 - Aug 11, 2005
      Role: Principal Investigator

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      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Castaldi A, Dodia RM, Orogo AM, Zambrano CM, Najor RH, Gustafsson ÅB, Heller Brown J, Purcell N. Decline in cellular function of aged mouse c-kit+ cardiac progenitor cells. J Physiol. 2017 Jul 24. PMID: 28737214.
        View in: PubMed
      2. Dusaban SS, Chun J, Rosen H, Purcell N, Brown JH. Sphingosine 1-phosphate receptor 3 and RhoA signaling mediate inflammatory gene expression in astrocytes. J Neuroinflammation. 2017 Jun 02; 14(1):111. PMID: 28577576.
        View in: PubMed
      3. Yung BS, Brand CS, Xiang SY, Gray CB, Means CK, Rosen H, Chun J, Purcell N, Brown JH, Miyamoto S. Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardioprotection. J Mol Cell Cardiol. 2017 Feb; 103:1-10. PMID: 28017639.
        View in: PubMed
      4. Castaldi A, Chesini GP, Taylor AE, Sussman MA, Brown JH, Purcell N. Sphingosine 1-phosphate elicits RhoA-dependent proliferation and MRTF-A mediated gene induction in CPCs. Cell Signal. 2016 08; 28(8):871-9. PMID: 27094722; PMCID: PMC5004781 [Available on 08/01/17].
      5. Kim K, Qiang L, Hayden MS, Sparling DP, Purcell N, Pajvani UB. mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2. Nat Commun. 2016 Jan 08; 7:10255. PMID: 26743335; PMCID: PMC4729872.
      6. Moc C, Taylor AE, Chesini GP, Zambrano CM, Barlow MS, Zhang X, Gustafsson ÅB, Purcell N. Physiological activation of Akt by PHLPP1 deletion protects against pathological hypertrophy. Cardiovasc Res. 2015 Feb 01; 105(2):160-70. PMID: 25411382; PMCID: PMC4303795.
      7. Dusaban SS, Purcell N, Rockenstein E, Masliah E, Cho MK, Smrcka AV, Brown JH. Phospholipase C epsilon links G protein-coupled receptor activation to inflammatory astrocytic responses. Proc Natl Acad Sci U S A. 2013 Feb 26; 110(9):3609-14. PMID: 23401561; PMCID: PMC3587233.
      8. Ling H, Gray CB, Zambon AC, Grimm M, Gu Y, Dalton N, Purcell N, Peterson K, Brown JH. Ca2+/Calmodulin-dependent protein kinase II d mediates myocardial ischemia/reperfusion injury through nuclear factor-?B. Circ Res. 2013 Mar 15; 112(6):935-44. PMID: 23388157; PMCID: PMC3673710.
      9. Chen B, Van Winkle JA, Lyden PD, Brown JH, Purcell N. PHLPP1 gene deletion protects the brain from ischemic injury. J Cereb Blood Flow Metab. 2013 Feb; 33(2):196-204. PMID: 23072745; PMCID: PMC3564187.
      10. Scimia MC, Hurtado C, Ray S, Metzler S, Wei K, Wang J, Woods CE, Purcell N, Catalucci D, Akasaka T, Bueno OF, Vlasuk GP, Kaliman P, Bodmer R, Smith LH, Ashley E, Mercola M, Brown JH, Ruiz-Lozano P. APJ acts as a dual receptor in cardiac hypertrophy. Nature. 2012 Aug 16; 488(7411):394-8. PMID: 22810587; PMCID: PMC3422434.
      11. Tao G, Levay AK, Peacock JD, Huk DJ, Both SN, Purcell N, Pinto JR, Galantowicz ML, Koch M, Lucchesi PA, Birk DE, Lincoln J. Collagen XIV is important for growth and structural integrity of the myocardium. J Mol Cell Cardiol. 2012 Nov; 53(5):626-38. PMID: 22906538; PMCID: PMC3472103.
      12. Xiang SY, Vanhoutte D, Del Re DP, Purcell N, Ling H, Banerjee I, Bossuyt J, Lang RA, Zheng Y, Matkovich SJ, Miyamoto S, Molkentin JD, Dorn GW, Brown JH. RhoA protects the mouse heart against ischemia/reperfusion injury. J Clin Invest. 2011 Aug; 121(8):3269-76. PMID: 21747165; PMCID: PMC3148727.
      13. Miyamoto S, Purcell N, Smith JM, Gao T, Whittaker R, Huang K, Castillo R, Glembotski CC, Sussman MA, Newton AC, Brown JH. PHLPP-1 negatively regulates Akt activity and survival in the heart. Circ Res. 2010 Aug 20; 107(4):476-84. PMID: 20576936; PMCID: PMC2957297.
      14. Maillet M, Purcell N, Sargent MA, York AJ, Bueno OF, Molkentin JD. DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. J Biol Chem. 2008 Nov 07; 283(45):31246-55. PMID: 18753132; PMCID: PMC2576531.
      15. Purcell N, Wilkins BJ, York A, Saba-El-Leil MK, Meloche S, Robbins J, Molkentin JD. Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo. Proc Natl Acad Sci U S A. 2007 Aug 28; 104(35):14074-9. PMID: 17709754; PMCID: PMC1955824.
      16. Baines CP, Kaiser RA, Purcell N, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 2005 Mar 31; 434(7033):658-62. PMID: 15800627.
        View in: PubMed
      17. Lips DJ, Bueno OF, Wilkins BJ, Purcell N, Kaiser RA, Lorenz JN, Voisin L, Saba-El-Leil MK, Meloche S, Pouysségur J, Pagès G, De Windt LJ, Doevendans PA, Molkentin JD. MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo. Circulation. 2004 Apr 27; 109(16):1938-41. PMID: 15096454.
        View in: PubMed
      18. Purcell N, Darwis D, Bueno OF, Müller JM, Schüle R, Molkentin JD. Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes. Mol Cell Biol. 2004 Feb; 24(3):1081-95. PMID: 14729955; PMCID: PMC321437.
      19. Purcell N, Molkentin JD. Is nuclear factor kappaB an attractive therapeutic target for treating cardiac hypertrophy? Circulation. 2003 Aug 12; 108(6):638-40. PMID: 12912791.
        View in: PubMed
      20. Gupta S, Purcell N, Lin A, Sen S. Activation of nuclear factor-kappaB is necessary for myotrophin-induced cardiac hypertrophy. J Cell Biol. 2002 Dec 23; 159(6):1019-28. PMID: 12486112; PMCID: PMC2173971.
      21. Tang G, Minemoto Y, Dibling B, Purcell N, Li Z, Karin M, Lin A. Inhibition of JNK activation through NF-kappaB target genes. Nature. 2001 Nov 15; 414(6861):313-7. PMID: 11713531.
        View in: PubMed
      22. Purcell N, Tang G, Yu C, Mercurio F, DiDonato JA, Lin A. Activation of NF-kappa B is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. Proc Natl Acad Sci U S A. 2001 Jun 05; 98(12):6668-73. PMID: 11381115; PMCID: PMC34410.
      23. Purcell N, Yu C, He D, Xiang J, Paran N, DiDonato JA, Yamaoka S, Shaul Y, Lin A. Activation of NF-kappaB by hepatitis B virus X protein through an IkappaB kinase-independent mechanism. Am J Physiol Gastrointest Liver Physiol. 2001 Apr; 280(4):G669-77. PMID: 11254493.
        View in: PubMed
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