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McKinsey Lab

Molecular Mechanisms of Heart Failure


Our lab is focused on​ underst​anding the signaling and gene regulatory mechanisms that control heart failure and associated disorders. We are particularly interested in the​ role of epigenetics in regulating the pathological cardiac hypertrophy and fibrosis that is associated with heart failure. Nuclear DNA is wound around proteins called histones to form chromatin, and post-translational modification of histones represents one epigenetic mechanism for altering gene expression. Among the enzymes that target histones are histone deacetylases (HDACs), histone acetyltransferases (HATs) and histone methyltransferases. We use molecular biology, biochemistry and pharmacology to address the roles of these and other epigenetic modifiers in the control of gene expression in the heart, and extend our findings to surgical, transgenic and gene knockout models of heart failure. Our animal model studies involve echocardiographic and catheter-based measurements of heart function​.

We are also interested in the mechanisms whereby signals derived from cell surface receptors are conveyed to histone-modifying enzymes by proteins kinases and phosphatases. The long-term goal of our work is to translate basic discoveries to novel therapies for patients with heart failure, which afflicts millions of adults in the U.S. and is associated with a 5-year mortality rate of nearly 50%. As such, our lab has established core expertise to enable in vitro, cellular and in vivo assessment of experimental small molecule compounds in support of early stage drug discovery.

Our lab emphasizes teamwork and camaraderie, thus creating an exciting environment for students and postdoctoral trainees.

Timothy A. McKinsey, Ph.D.
School of Medicine, Division of Cardiology
University of Colorado Denver
Anschutz Medical Campus
12700 E. 19th Ave
Aurora, CO 80045-0508
Tel: (303) 724-5476 ​​​​ ​​​​​​​​ ​​​​​​​​​​​​​​​​​​​​​​​ ​​​​​​​​​​​​​​​​​​​​​​​​
  • Cardiac Phy​siolo​​g​y  alt=

  • Cardiac Fibro​sis alt=

  • Cardiac Hypertrophy  alt=

  • Pharmacology and High Throughput Chemical Biology  alt=

  • Signaling and Gene Regulation  alt=



  •  alt=​Timothy McKinsey, Ph.D.

    Associate Professor and
    Associate Division Head for Translational Research

    School of Medicine
    Division of Cardiology,
    Member/Training Faculty:
    - Molecular and Cellular Pharmacology PhD Program
    - Biomedical Sciences PhD Training Program
    - Medical Scientist MD/PhD Training Program
  • Maria Cavasin, Ph.D.

    Senior Research Associate
    School of Medicine
    Divison of Cardiology

Postdoctoral Researchers

  •  alt=Bradley Ferguson, Ph.D.

    School of Medicine
    Divison of Cardiology
    B.S. - Appalachian State University
    M.S., Ph.D. - University of North Carolina-Greensboro
  • Matthew Stratton, Ph.D.

    School of Medicine
    Divison of Cardiology
    B.S. - Duquesne University
    M.S. - University of Wyoming
    Ph.D. - Colorado State University


  •  alt=Katherine Schuetze, M.D.

    School of Medicine
    Divison of Cardiology
    B.S. - University of Colorado-Boulder
    Medical School - University of Colorado-Denver
    Residency - University of Michigan

Graduate Students

  •  alt=Weston Blakeslee

    School of Medicine
    Divison of Cardiology,
    Division of Pharmacology
    B.S. - University of Colorado-Boulder
  • Philip Tatman

    School of Medicine
    Medical Scientist Training Program
    B.S. - University of Washington

Research Staff

Undergraduate Students



Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner.

Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle.

Acetyl-lysine erasers a​nd readers in the control of pulmonary hypertension and right ventricular hypertrophy.​

Non-sirtuin histone deacetylases in the control of cardiac aging.

AKT Network of Genes and Impaired Myocardial Contractility During Murine Acute Chagasic Myocarditis.

Tubulin hyperacetylation is adaptive in cardiac proteotoxicity by promoting autophagy.

Inflammatory cytokines epigenetically regulate rheumatoid arthritis fibroblast-like synoviocyte activation by suppressing HDAC5 expression.

Class I HDAC inhibition stimulates cardiac protein SUMOylation through a post-translational mechanism.

Reversal of severe angioproliferative pulmonary arterial hypertension and right ventricular hypertrophy by combined phosphodiesterase-5 and endothelin receptor inhibition.

BET-ting on chromatin-based therapeutics for heart failure.

HDAC6 contributes to pathological responses of heart and skeletal muscle to chronic angiotensin-II signaling.

Endoplasmic reticulum stress effector CCAAT/enhancer-binding protein homologous protein (CHOP) regulates chronic kidney disease-induced vascular calcification.

Targeting cardiac fibroblasts to treat fibrosis of the heart: focus on HDACs.

Class I HDACs regulate angiotensin II-dependent cardiac fibrosis via fibroblasts and circulating fibrocytes.

BET acetyl-lysine binding proteins control pathological cardiac hypertrophy.

Signal-dependent repression of DUSP5 by class I HDACs controls nuclear ERK activity and cardiomyocyte hypertrophy. ​​​​
The UC Pre-Clinical Cardiovascular Core offers a variety of pre-clinical models in rats and mice, from development to analysis. The Core's main therapeutic areas are cardiovascular, renal, and pulmonary.​​