Timothy D. O'Connell, PhD

Assistant Professor, Department of Integrative Biology and Physiology (IBP)

Timothy D. O'Connell

Contact Info


Office Phone 612-625-6750

Fax 612-625-5149

Office Address:
3-141 CCRB
2231 6th St. SE
Minneapolis, MN 55455

Mailing Address:
Cancer & Cardiovascular Research Building
2231 6th St. SE
Minneapolis, MN 55455

PhD, University of Michigan (Pharmacology), 1995

BSc, The University of Illinois at Chicago (Bioengineering, College of Engineering),1990


Awards & Recognition

  • Finalist for the Richard J. Bing Young Investigator Award (ISHR) AHA Young Investigator Award for Advances in the Molecular and Cellular Mechanisms of Heart Failure Meeting, Snowbird, Utah, 2001
  • Cardiovascular Research Institute Postdoctoral Fellowship, The University of California at San Francisco, 1995-1998
  • Rackham Dissertation Award, Horace H. Rackham School of Graduate Studies, The University of Michigan, 1994
  • Pharmacological Sciences Training Program Grant (NIH/NIGMS Grant GM-7767) at The University of Michigan, 1990-1995
  • Graduated with College Honors with a B.Sc. in Bioengineering from The University of Illinois at Chicago 1990 1st Place, Engineering Exposition, The University of Illinois at Chicago. Project title: Optical Scattering Measurements of Isolated Contracting Myocytes, 1990


Research Summary/Interests

The focus of the O'Connell lab is to advance the science of heart failure treatment and prevention. One prevailing theory to explain the development and progression of heart failure is hyperactivity of the sympathetic nervous system (SNS). The SNS controls the release of the hormone norepinephrine from nerve terminals, which causes activation of adrenergic receptors leading to cellular response. In heart disease, the activity of the SNS is increased in almost all cases, regardless of the underlying cause of the disease. This hyperactivity is detrimental to the heart, and ultimately leads to cardiac cell death, loss of contractile function, dilation of the heart and death.

Current heart failure therapy is to use a class of drugs known as beta-blockers, which block the action of norepinephrine at beta-adrenergic receptors. Although beta-blockers improve symptoms in heart failure patients, heart failure remains a leading killer in the US, and therefore novel treatments are constantly being sought. In our laboratory, we investigate another type of adrenergic receptor, known as the alpha-1-adrenergic receptor (alpha-1-AR). Using mice in which we have deleted the genes for the subtypes of alpha-1-ARs found in the heart (alpha-1-knockout mice), we demonstrated that alpha-1-ARs are required for postnatal hypertrophy of the heart and for the heart to adapt to stress. In other words, alpha-1-ARs receptors, unlike beta-ARs, play a protective role in the heart.

Our labs investigate the mechanisms by which alpha-1-ARs protect the heart from stress. We will use animal models in which we impose a laboratory model of heart failure in alpha-1-transgenic mice as well as approaches in cardiac cells cultured from alpha-1-knockout mice to study alpha-1-AR function in the heart. The ultimate goal is to determine if an alpha-1-activator would benefit heart failure patients.


PUBMED Link to Publications

  • Wright C.D., S.C. Wu, E.F. Dahl, A.J. Sazama, and T.D. O'Connell. Nuclear localization drives ?1-adrenergic receptor oligomerization and signaling in cardiac myocytes. Cell Signal. 2012 Mar;24(3):794-802. PMID: 22120526
  • Wright CD, Chen Q, Baye NL, Huang Y, Healy CL, Kasinathan S, and O'Connell TD. 2008. Nuclear alpha1-Adrenergic Receptors Signal Activated ERK Localization to Caveolae in Adult Cardiac Myocytes. Circ. Res. 103: 992-1000.
  • Huang Y, Wright CD, Kobayashi S, Healy CL, Elgethun M, Cypher, A, Liang Q and O'Connell TD. 2008. GATA4 Is a Survival Factor in Adult Cardiac Myocytes, but Is Not Required for alpha1A-Adrenergic Receptor Survival Signaling. Amer. J. Physiol. Heart Circ. Physiol. 295: H699-707.
  • Kobayashi S, Mao K, Zheng H, Wang X, Patterson C, O'Connell TD, and Liang Q. 2007. Diminished GATA4 protein levels contribute to hyperglycemia-induced cardiomyocyte injury. J. Biol. Chem. 282: 21945-21952.