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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
    Division of Cardiology

Postdoctoral Researchers

  •  alt=Bradley Ferguson, Ph.D.

    School of Medicine
    Division 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=Rushita Bagchi, Ph.D.

    School of Medicine
    Division of Cardiology
    B.S., M.S. - University of Baroda (India)
    Ph.D. - University of Manitoba
  • Adam Beharry, Ph.D.

    School of Medicine
    Division of Cardiology
    B.S. - University of South Carolina
    M.S. - The Citadel
    Ph.D. - University of Florida
  • Ying Hsi (Alvin) Lin, Ph.D.

    School of Medicine
    Division of Cardiology
    B.S. - National Taiwan University
    M.S. - National Taiwan University
    Ph.D. - University of Illinois at Chicago


  •  alt=Katherine Schuetze, M.D.

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

Graduate Students

  •  alt=Weston Blakeslee, B.S.

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

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

Research Staff

Undergraduate Students



High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling. Zhao Y, Londono P, Cao Y, Sharpe EJ, Proenza C, O'Rourke R, Jones KL, Jeong MY, Walker LA, Buttrick PM, McKinsey TA, Song K. Nat Commun. 2015 Sep 10;6:8243. doi: 10.1038/ncomms9243. PMID: 26354680​

TNAP: a new player in cardiac fibrosis? Focus on "Tissue-nonspecific alkaline phosphatase as a target of sFRP2 in cardiac fibroblasts". Schuetze KB, McKinsey TA. Am J Physiol Cell Physiol. 2015 Aug 1;309(3):C137-8. doi: 10.1152/ajpcell.00167.2015. Epub 2015 Jun 24. PMID: 26108666​

Emerging roles for histone deacetylases in pulmonary hypertension and right ventricular remodeling (2013 Grover Conference series). Cavasin MA, Stenmark KR, McKinsey TA. Pulm Circ. 2015 Mar;5(1):63-72. doi: 10.1086/679700. Review. PMID: 25992271​

Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner. Stauffer BL, Dockstader K, Russell G, Hijmans J, Walker L, Cecil M, Demos-Davies K, Medway A, McKinsey TA, Sucharov CC. Biochem Biophys Res Commun. 2015 Jun 26;462(2):131-7. doi: 10.1016/j.bbrc.2015.04.106. Epub 2015 Apr 29. PMID: 25935483

Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle. Lemon DD, Harrison BC, Horn TR, Stratton MS, Ferguson BS, Wempe MF, McKinsey TA. FEBS Lett. 2015 Apr 28;589(10):1080-8. doi: 10.1016/j.febslet.2015.03.017. Epub 2015 Mar 25. PMID: 25816750 

Acetyl-lysine erasers a​nd readers in the control of pulmonary hypertension and right ventricular hypertrophy.​ Stratton MS, McKinsey TA. Biochem Cell Biol. 2015 Apr;93(2):149-57. doi: 10.1139/bcb-2014-0119. Epub 2014 Dec 16. Review. PMID: 25707943

Non-sirtuin histone deacetylases in the control of cardiac aging. Ferguson BS, McKinsey TA. J Mol Cell Cardiol. 2015 Jun;83:14-20. doi: 10.1016/j.yjmcc.2015.03.010. Epub 2015 Mar 16. Review. PMID: 25791169

AKT Network of Genes and Impaired Myocardial Contractility During Murine Acute Chagasic Myocarditis. Henao-Martínez AF, Agler AH, Watson AM, Hennessy C, Davidson E, Demos-Davies K, McKinsey TA, Wilson M, Schwartz DA, Yang IV. Am J Trop Med Hyg. 2015 Mar;92(3):523-9. doi: 10.4269/ajtmh.14-0433. Epub 2015 Jan 12. PMID: 25582694

Tubulin hyperacetylation is adaptive in cardiac proteotoxicity by promoting autophagy. McLendon PM, Ferguson BS, Osinska H, Bhuiyan MS, James J, McKinsey TA, Robbins J. Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):E5178-86. doi: 10.1073/pnas.1415589111. Epub 2014 Nov 17. PMID: 25404307

Inflammatory cytokines epigenetically regulate rheumatoid arthritis fibroblast-like synoviocyte activation by suppressing HDAC5 expression. Angiolilli C, Grabiec AM, Ferguson BS, Ospelt C, Malvar Fernandez B, van Es IE, van Baarsen LG, Gay S, McKinsey TA, Tak PP, Baeten DL, Reedquist KA. Ann Rheum Dis. 2014 Dec 1. pii: annrheumdis-2014-205635. doi: 10.1136/annrheumdis-2014-205635. [Epub ahead of print] PMID: 25452308

Class I HDAC inhibition stimulates cardiac protein SUMOylation through a post-translational mechanism. Blakeslee WW, Wysoczynski CL, Fritz KS, Nyborg JK, Churchill ME, McKinsey TA. Cell Signal. 2014 Dec;26(12):2912-20. doi: 10.1016/j.cellsig.2014.09.005. Epub 2014 Sep 16. PMID: 25220405

Reversal of severe angioproliferative pulmonary arterial hypertension and right ventricular hypertrophy by combined phosphodiesterase-5 and endothelin receptor inhibition. Cavasin MA, Demos-Davies KM, Schuetze KB, Blakeslee WW, Stratton MS, Tuder RM, McKinsey TA. J Transl Med. 2014 Nov 26;12:314. doi: 10.1186/s12967-014-0314-y. PMID: 25425003

BET-ting on chromatin-based therapeutics for heart failure. Haldar SM, McKinsey TA. J Mol Cell Cardiol. 2014 Sep;74:98-102. doi: 10.1016/j.yjmcc.2014.05.002. Epub 2014 May 14. Review. PMID: 24838003

HDAC6 contributes to pathological responses of heart and skeletal muscle to chronic angiotensin-II signaling. Demos-Davies KM, Ferguson BS, Cavasin MA, Mahaffey JH, Williams SM, Spiltoir JI, Schuetze KB, Horn TR, Chen B, Ferrara C, Scellini B, Piroddi N, Tesi C, Poggesi C, Jeong MY, McKinsey TA. Am J Physiol Heart Circ Physiol. 2014 Jul 15;307(2):H252-8. doi: 10.1152/ajpheart.00149.2014. Epub 2014 May 23. PMID: 24858848

Endoplasmic reticulum stress effector CCAAT/enhancer-binding protein homologous protein (CHOP) regulates chronic kidney disease-induced vascular calcification. Miyazaki-Anzai S, Masuda M, Demos-Davies KM, Keenan AL, Saunders SJ, Masuda R, Jablonski K, Cavasin MA, Kendrick J, Chonchol M, McKinsey TA, Levi M, Miyazaki M. J Am Heart Assoc. 2014 Jun 24;3(3):e000949. doi: 10.1161/JAHA.114.000949. PMID: 24963104

Targeting cardiac fibroblasts to treat fibrosis of the heart: focus on HDACs. Schuetze KB, McKinsey TA, Long CS. J Mol Cell Cardiol. 2014 May;70:100-7. doi: 10.1016/j.yjmcc.2014.02.015. Epub 2014 Mar 11. Review. PMID: 24631770

Class I HDACs regulate angiotensin II-dependent cardiac fibrosis via fibroblasts and circulating fibrocytes. Williams SM, Golden-Mason L, Ferguson BS, Schuetze KB, Cavasin MA, Demos-Davies K, Yeager ME, Stenmark KR, McKinsey TA. J Mol Cell Cardiol. 2014 Feb;67:112-25. doi: 10.1016/j.yjmcc.2013.12.013. Epub 2013 Dec 26. PMID: 24374140

BET acetyl-lysine binding proteins control pathological cardiac hypertrophy. Spiltoir JI, Stratton MS, Cavasin MA, Demos-Davies K, Reid BG, Qi J, Bradner JE, McKinsey TA. J Mol Cell Cardiol. 2013 Oct;63:175-9. doi: 10.1016/j.yjmcc.2013.07.017. Epub 2013 Aug 9. PMID: 23939492

Signal-dependent repression of DUSP5 by class I HDACs controls nuclear ERK activity and cardiomyocyte hypertrophy. Ferguson BS, Harrison BC, Jeong MY, Reid BG, Wempe MF, Wagner FF, Holson EB, McKinsey TA. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9806-11. doi: 10.1073/pnas.1301509110. Epub 2013 May 29. PMID: 23720316 ​​​​
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.​​