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O'Connell Lab Publications

Our landmark publications:

The α1A/C - and α1B-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse

     This paper was the first report to demonstrate that α1-adrenergic receptors are required for physiologic postnatal hypertrophy in heart and required for an adaptive response to pathologic stimuli in the heart. Prior to this report, convention indicated that all receptors that Gαq receptors, like α1-adrenergic receptors, induce pathologic remodeling in heart. Therefore, this paper redines the classic dogma of Gq-receptor signaling in heart.

 

  • O'Connell TD, Ishizaka S, Nakamura A, Swigart PM, Rodrigo MC, Simpson GL, Cotecchia S, Rokosh DG, Grossman W, Foster E, Simpson PC. J Clin Invest. 2003 Jun;111(11):1783-91

Nuclear α1-Adrenergic Receptors Signal Activated ERK Localization to Caveolae in Adult Cardiac Myocytes

     G-protein coupled receptors are classically believed to function at the cell surface and mediate 'outside-in' signaling to mediate cell function. This paper demonstrated for the first time that endogenous α1-adrenergic receptors localize to and signal at the nucleus in adult cardiac myocytes. This is in contrast to other Gq-receptors like angiotensin and endothelin receptors, which predominantly but not exclusively are found at the cell surface in adult cardiac myocytes. Together with our finding that α1-adrenergic receptors are cardioprotective, the idea that α1-adrenergic receptors localize to the nucleus form the basis of our hypothesis that Gq-receptor signaling is compartmentalized and nuclear Gq-receptor signaling is cardioprotective. 

 

  • Wright CD, Chen Q, Baye NL, Huang Y, Healy CL, Kasinathan S, O'Connell TD. Circ Res 2008 Oct 24;103(9):992-1000

 

Omega-3 Fatty Acids Prevent Pressure Overload Induced Cardiac Fibrosis Through Activation of Cyclic GMP/Protein Kinase G Signaling in Cardiac Fibroblasts

     Omega-3 fatty acids prevent sudden death in coronary heart disease, although other protective benefits have yet to be identified. This paper demonstrated for the first time that omega-3 fatty acids prevent fibrosis by blocking activation of fibroblasts, and in so doing, prevent diastolic dysfunction in a mouse model of hypertensive heart disease. Clinically, our findings suggest that omega-3 fatty acids could be useful in preventing fibrosis in patients with hypertensive heart disease and heart failure with preserved ejection fraction, a clinical syndrome for which there is no proven therapy.

 

  • Chen J, Shearer GC, Chen Q, Healy CL, Beyer AJ, Nareddy VB, Gerdes AM, Harris WS, O'Connell TD, Wang D. Circulation 2011 Feb 15;123(6):584-93

Click here for the PDF to our 2008 Circulation Research cover story.

Click here for the PDF to our 2014 Pharmacological Reviews cover story.

A comprehensive publication list:

Click here for the most up-to-date PubMed list of publications.

2019

  • Dahl EF, Wu SC, Healy CL, Perry J, O'Connell TD. 2019. ERK mediated survival signaling is dependent on the Gq-G-protein coupled receptor type and subcellular localization in adult cardiac myocytes. J Mol Cell Cardiol. PMID: 30528765

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2018

  • Dahl EF, Wu SC, Healy CL, Harsch BA, Shearer GC, O'Connell TD. 2018. Subcellular compartmentalization of proximal Gαq-receptor signaling produces unique hypertrophic phenotypes in adult cardiac myocytes. J Biol Chem. PMID: 29610273

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2017

  • O'Connell TD, Block RC, Huang SP, Shearer GC. 2017. ω3-Polyunsaturated fatty acids for heart failure: Effects of dose on efficacy and novel signaling through free fatty acid receptor 4. J Mol Cell Cardiol. PMID: 27986444

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2016

  • Chen X, O'Connell TD, Xiang YK. 2016. With or without Langendorff: A new method for adult myocyte isolation to be tested with time. Circ Res. PMID: 27688302.

  • O'Connell TD, Block RC, Huang SP, and Shearer GC. 2016. Omega-3-Polyunsaturated fatty acids for heart failure: effects of dose on efficacy and novel signaling through free fatty acid receptor 4. J Mol Cell Cardiol. PMID: 27986444

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2015

  • Dahl EF, Wright CD, O'Connell TD. 2015. Quantification of catecholamine uptake in adult cardiac myocytes. Methods Mol Biol. PMID: 25304347.

  • Zhang L, Guo J, Zhang P, Xiong Q, Wu SC, Xia L, Roy SS, Tolar J, O'Connell TD, Kyba M, Liao K, Zhang J. 2015. Derivation and high engraftment of patient-specific cardiomyocyte-sheet using induced pluripotent stem cells generated from adult cardiac fibroblast. Circ Heart Fail. PMID: 25420485.

  • Eclov JA, Qian Q, Redetke R, Chen Q, Wu SC, Healy CL, Ortmeier SB, Harmon E, Shearer GC, O'Connell TD. 2015. EPA, not DHA, prevents fibrosis in pressure overload induced heart failure; potential role of free fatty acid receptor 4. J Lipid Res. PMID: 26435012.

 

2014

  • Wu SC, O'Connell TD. 2014. A nuclear option? G-protein coupled receptors at the nucleus in cardiac myocytes.  J Cardiovasc Pharmacol. PMID: 25551323.

  • Wu SC, O'Connell TD. 2014. Nuclear Compartmentalization of α1-Adrenergic Receptor Signaling in Adult Cardiac Myocytes. J Cardiovasc Pharmacol. PMID: 25264754.

  • Wu SC, Dahl EF, Wright CD, Cypher AL, Healy CL, O'Connell TD. 2014. Nuclear localization of α1A-adrenergic receptors is required for signaling in cardiac myocytes: an "inside-out" α1-AR signaling pathway. J Am Heart Assoc. PMID: 24772522.

  • Hall JL, O'Connell TD, Francis GS. 2014. Promising small molecule for heart failure targeting adrenal catecholamine release and β-adrenergic receptor signaling in the heart. J Am Coll Cardiol. PMID: 24703911.

  • Jensen BC, O'Connell TD, Simpson PC. 2014. Alpha-1-adrenergic receptors in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation. J Cardiovasc Pharmacol. PMID: 24145181.

  • O'Connell TD, Jensen BC, Baker AJ, Simpson PC. 2014. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. PMID: 24368739.

 

2012

  • Wright CD, Wu SC, Dahl EF, Sazama AJ, O'Connell TD. 2012. Nuclear localization drives α1-adrenergic receptor oligomerization and signaling in cardiac myocytes. Cell Signal. PMID: 22120526.

 

2011

  • Chen J, Shearer GC, Chen Q, Healy CL, Beyer AJ, Gerdes AM, Harris WS, O’Connell TD, Wang D. 2011. ω-3 fatty acids prevent pressure overload-induced cardiac fibrosis through activation of cGMP/PKG signaling in cardiac fibroblasts. Circulation. PMID: 21282499.

  • Jensen, BC, O’Connell TD, Simpson PC. 2011. Alpha-1-adrenergic receptors: Targets for agonist drugs to treat heart failure. J. Mol. Cell. Cardiol. PMID: 21118696. 

 

2010

  • Chen Q, Williams R, Healy CL, Wright CD, Wu SC, O’Connell TD. 2010. An association between gene expression and better survival in female mice following myocardial infarction. J. Mol. Cell. Cardiol. PMID: 20692266.

 

2008

  • Huang Y, Wright CD, Kobayashi S, Healy CL,  Elgethun M, Cypher A, Liang Q, O’Connell TD. 2008. GATA4 is a survival factor in adult cardiac myocytes, but is not required for α1A-adrenergic receptor survival signaling. Amer. J. Physiol. Heart Circ. Physiol. PMID: 18552157.

  • Wright CD, Chen QH, Baye NL, Huang Y, Merkwan CL, Kasinathan S, O’Connell TD. 2008. Nuclear α1-adrenergic receptors signal activated ERK localization to caveolae in adult cardiac myocytes. Circ. Res. PMID: 18802028.

 

2007

  • Huang Y, Wright CD, Merkwan CL, Baye NL, Liang Q, Simpson PC, O’Connell TD. 2007. An α1A-adrenergic-extracellular signal-regulated kinase survival signaling pathway in cardiac myocytes. Circulation. PMID: 17283256. 

  • O’Connell TD, Rodrigo MC, Simpson PC. 2007. Isolation and culture of adult mouse cardiac myocytes. Methods Mol Biol. PMID: 17172694.

  • Kuzman JA, O’Connell TD, Gerdes AM. 2007. Rapamycin prevents thyroid hormone induced cardiac hypertrophy. Endocrinol. PMID: 17395699. 

  • Kobayashi S, Mao K, Zheng H, Wang X, Patterson C, O’Connell TD, Liang Q. 2007. Diminished GATA4 levels contribute to hyperglycemia-induced cardiomyocyte injury. J. Biol. Chem. PMID: 17525155. 

 

2006

  • O’Connell TD, Swigart PS, Rodrigo MC, Ishizaka S, Joho S, Foster E, Grossman W, Simpson PC. 2006, α1-Adrenregic receptors prevent a maladaptive response to pressure overload.  J. Clin. Invest. PMID: 16585965. 

 

2004

  • Okoshi, MP, Yan X, Okoshi K, Nakayama M, Schuldt AJ, O’Connell TD, Simpson PC, Lorell BH. 2004. Aldosterone directly stimulates cardiac myocyte hypertrophy. J. Card. Fail. PMID: 15599842. 

 

2003

  • Turnbull L, McCloskey DT, O’Connell TD, Simpson PC, Baker AJ. 2003. α1-Adrenergic receptor responses in α1-AB-AR knockout mouse hearts suggest the presence of α1D-AR. Am. J. Physiol. (Heart Circ. Physiol.) PMID: 12595294.

  • O’Connell TD, Ishizaka S, Nakamura A, Swigart PS, Rodrigo MC, Simpson GL, Cotecchia S, Rokosh DG, Grossman W, Foster E, Simpson PC. 2003. The α1A/C- and α1B-adrenergic receptors are required for physiological hypertrophy in the double-knockout mouse  J. Clin. Invest. PMID: 12782680. 

  • McCloskey DT, O’Connell TD, Simpson PC, Baker AJ. 2003. Abnormal myocardial contraction in α1A- and α1B-adrenoceptor double knockout mice. J. Mol. Cell. Card. PMID:14519431. 

 

2002

  • McCloskey DT, Rokosh DG, O’Connell TD, Keung EC, Simpson PC, Baker AJ. 2002. α1-adrenoceptor subtypes mediate negative inotropy in myocardium from α1A/C-knockout and wild type mice. J. Mol. Cell. Cardiol. PMID: 12234770

  • Gilman AG et al. 2002. Overview of the Alliance for Cellular Signaling. Nature PMID: 12478301.

  • Sambrano GR, Fraser I, Han H, Ni Y, O’Connell TD, Yan Z, and Stull JT. 2002 Navigating the signaling network in mouse cardiac myocytes. Nature PMID: 12478303.

 

2001

  • O’Connell TD, Rokosh DG, Simpson PC. 2001. Cloning and characterization of the mouse α1C-adrenergic receptor gene and analysis of an α1C promoter in cardiac myocytes: Role of an MCAT element that binds transcriptional enhancer factor 1 (TEF-1). Mol. Pharmacol. PMID: 11306707. 

 

1998

  • Simpson RU, O'Connell TD, Pan Q, Newhouse J, Somerman MJ. 1998. Antisense oligonucleotides targeted against protein kinase Cbeta and CbetaII block 1,25-(OH)2D3-induced differentiation. J Biol Chem. PMID: 9677384.

 

1997

  • Pan Q, Granger J, O'Connell TD, Somerman MJ, Simpson RU. 1997. Promotion of HL-60 cell differentiation by 1,25-dihydroxyvitamin D3 regulation of protein kinase C levels and activity. Biochem Pharmacol. PMID:9354591.

  • O'Connell TD, Berry JE, Jarvis AK, Somerman MJ, Simpson RU. 1997. 1,25-Dihydroxyvitamin D3 regulation of cardiac myocyte proliferation and hypertrophy. Am J Physiol. PMID: 9139959.

 

1996

  • O'Connell TD, Berry JE, Jarvis AK, Somerman MJ, Simpson RU. 1996. 1,25-Dihydroxyvitamin D3-regulated binding of nuclear proteins to a c-myc intron element. Endocrinology. PMID: 8828471.

  • O'Connell TD, Simpson RU. 1996. Immunochemical identification of the 1,25-dihydroxyvitamin D3 receptor protein in human heart. Cell Biol Int. PMID: 8948124.

 

1995

  • O'Connell TD, Simpson RU. 1995. 1,25-Dihydroxyvitamin D3 regulation of myocardial growth and c-myc levels in the rat heart. Biochem Biophys Res Commun. PMID: 7639762.

  • O'Connell TD, Giacherio DA, Jarvis AK, Simpson RU. 1995. Inhibition of cardiac myocyte maturation by 1,25-dihydroxyvitamin D3. Endocrinology. PMID: 7835280.

 

1994

  • O'Connell TD, Weishaar RE, Simpson RU. 1994. Regulation of myosin isozyme expression by vitamin D3 deficiency and 1,25-dihydroxyvitamin D3 in the rat heart. Endocrinology. PMID: 8299585.

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Electronic Publications:

  • Hsueh R, Roach T, Lin KM, O'Connell TD, Yan Z. Purification and characterization of mouse splenic B lymphocytes. AfCS Research Reports. 2002. http://www.signaling-gateway.org/

  • O'Connell TD, Ni YG, Lin KM, Han H, Yan Z. Isolation and culture of adult mouse cardiac myocytes for signaling studies. AfCS Research Reports. 2003. http://www.signaling-gateway.org/

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Chapters in Books:

  • O'Connell TD, Simpson RU. 1,25-Dihydroxyvitamin D3 and cardiac muscle structure and function. In: Crass and Avioli LV (eds.). Calcium-regulating hormones and cardiovascular function. 1995. CRC Press, Boca Raton.

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