McKinsey Lab

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 
timothy.mckinsey@cuanschutz.edu

McKinsey, TimTimothy McKinsey, Ph.D.

-Professor of Medicine
-Joseph and Rose LaConte
Cardiology Endowed Chair

-Division Head for Translational Research

Department of Medicine
Division of Cardiology​

 


Member/Trainin​g Faculty:
- Molecular and Cellular Pharmacology PhD Program
- Biomedical Sciences PhD Training Program
- Medical Scientist MD/PhD Training Program

timothy.mckinsey@cuanschutz.edu


Cavasin, MariaMaria Cavasin, Ph.D.

Senior Research Associate

Department of Medicine
Division of Cardiology

maria.cavasin@cuanschutz.edu

 

 

 


Post Doctoral Fellows


Bagchi, RushitaRushita Bagchi, Ph.D.

Department of Medicine
Division of Cardiology

B.S. University of Baroda (India)
M.S. University of Baroda (India)
Ph.D. University of Manitoba (Canada)

Rushita.Bagchi@cuanschutz.edu​

 

 


Emma Louise Robinson, PhD

Department of Medicine
Division of Cardiology

Master of Molecular & Cellular Biochemistry (MBiochem) St Hilda’s College, Oxford University, Oxford, UK
Master of Research (MRes), Emmanuel College, University of Cambridge, Cambridge, UK
Ph.D. in Biological Sciences, University of Cambridge, UK
Junior Postdoctoral training (2 years), Maastricht University, The Netherlands

Emma.2.Robinson@cuanschutz.edu


 ​Felisbino, MarinaMarina Felisbino, Ph.D.

Department of Medicine
Division of Cardiology

B.S. Biology
M.S. Structural and Cellular Biology
Ph.D. Structural and Cellular Biology, University of Campinas (Brazil)

Marina.Felisbino@cuanschutz.edu​




 

 


Major, JenniferJennifer Major, Ph.D. 

Department of Medicine
Division of Cardiology

B.S. Biology
M.S. Cellular and Molecular Medicine
Ph.D. Cellular and Molecular Medicine, University of Ottawa

Jennifer.Major@cuanschutz.edu​

 


​​​Travers, JoshJosh Travers, Ph.D.

Department of Medicine
Division of Cardiology

B.S. Biotechnology, Rochester Institute of Technology
Ph.D. Pharmacology, University of Cincinnati

Joshua.Travers@cuanschutz.edu​​

 


Rubino, MarcelloMarcello Rubino, Ph.D​.

Department of Medicine
Division of Cardiology

B.S. Faculty of Sciences. FF.NN, University of Ferrara, Italy
M.S. Biomolecular and Cellular Sciences, University of Ferrara, Italy
Ph.D. Experimental Pathology and Neuropathology Department of Research in Immunology and Inflammation; Humanita Clinical and Research Center 

Marcello.Rubino@cuanschutz.edu


Charley Tharp headshot

     Charley Tharp, M.D.

     Department of Medicine
     Division of Cardiology

     B.A. Molecular Biology, Colgate University, Hamilton, NY         
     M.D. University of Colorado School of Medicine
     Internal Medicine Residency: University of Colorado School of Medicine
     Cardiology Fellowship: University of Colorado School of  Medicine

                                                Charles.Tharp@cuanschutz.edu

 


Research Staff
___________________________________________________________

 

Elizabeth Hardy

     Elizabeth Hardy, M.S.

     Department of Medicine
     Division of Cardiology

     M.S. Biology
     University of Oklahoma

     Elizabeth.Hardy@cuanschutz.edu

 

 

Keenan Kaltenbacher     Keenan Kaltenbacher, B.S.

     Department of Medicine
     Division of Cardiology

     B.S Metropolitan State University

     Keenan.Kaltenbacher@cuanschutz.edu

 



Former Lab Members

 


Haefner, KoreyKorey Haefner, B.S.

B.S. University of Colorado Boulder
M.S. University of Colorado Boulder


Current Position:

Director of Finance and Administration at BioPIx, Inc. and Firebreak Biologics, Inc. 

 

 

 


Wennersten, SaraSara Wennersten, B.S.


B.S. Human Biology, Michigan State University

Current Position:

Department of Medicine
Division of Cardiology


sara.wennersten@ucdenver.edu


Stratton, MatthewMatthew Stratton, Ph.D.


B.S. Duquesne University
M.S. University of Wyoming
Ph.D. Colorado State University

Current Position:

Assistant P​rofessor
Ohio State University

matthew.stratton@osumc.edu


Weston Blakeslee, Ph.D.

B.S. University of Colorado Boulder
Ph.D. University of Colorado Denver-AMC​

Current Position:

Director of Clinical Pharmacology, RxREVU

weston.blakeslee@rxrevu.com



ferguson brad   Bradley Ferguson, Ph.D.

   B.S. Appalachian State University
   M.S./Ph.D. University of North Carolina- Greensboro

   Current Position:

   Assistant Professor,
   University of Nevada, Reno 

   bferguson@unr.edu

 


Sean wickers   Sean Wickers

   University of Denver​

   Current Position:

   Medical Student at University of  Colorado School of Medicine

   Sean.Wickers@cuanschutz.edu

 

 


Katherine Schuetze, M.D.

B.S. University of Colorado Boulder
M.D. University of Colorado Denver-AMC
Residency-University of Michigan

Current Position:

Interventional Cardiology at Banner Health Center
Greely, CO


Demos-Davies, KimKim Demos-Davies, B.A.

B.A. University of Colorado-Boulder​

Current Position:

Graduate Student,
DVM/Ph.D. Program
University of Minnesota

demos027@umn.edu



Schreiter, FriederikeFriederike Schreiter, M.S.

B.S. University of Heidelberg, Germany
M.S. University of Heidelberg, Germany​

Current Position:

Graduate Student (HBIGS)
Heidelberg Biosciences International Graduate School

friederike.schreiter@med.uni-heidelberg.de

Cardiac Physiology​

physiology

Cardiac Fibrosis​

Fibrosis

Cardiac Hypertrophy​

cardiomyocytehypertrophy

 

 

 

 

Pharmacology and High Throughput Chemical Biology

Pharmacology

Signaling and Gene Regulation

Signaling

     

2019 McKinsey Lab Holiday Lunch at Texas de Brazil

Holiday Lunch

McKinsey Lab 2019

McKinsey Lab 2019

2019 Birthday Lunch      

2019 Birthday Lunch 

2018 Tim's 50th

Tim's 50th March 20th 2018 smaller

2017 Hiking in Boulder

2017 Boulder Hike

2017 FASEB Meeting in Montana

2017 FASEB

2017 Lab Outing: Rockies Baseball Game

2017 Rockies Game - 12017 Rockies Game - 22017 Rockies Game - 32017 Rockies Game - 4

2016 Holiday Christmas Dinner

2016 Christmas Dinner - 12016 Christmas Dinner - 22016 Christmas Dinner - 32016 Christmas Dinner - 4

 

 


   


2020:

Site-specific acetyl-mimetic modification of cardiac troponin I modulates myofilament relaxation and calcium sensitivity

HDAC inhibition improves cardiopulmonary function in a feline model of diastolic dysfunction

2019:

Defining decreased protein succinylation of failing human cardiac myofibrils in ischemic cardiomyopathy

Transcatheter aortic valve replacements alter circulating serum factors to mediate myofibroblast deactivation

Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation

Physiological Biomimetic Culture System for Pig and Human Heart Slices

Putting the Heat on Cardiac Fibrosis: Hsp20 Regulates Myocyte-To-Fibroblast Crosstalk

Gold Nanoparticle-Functionalized Reverse Thermal Gel for Tissue Engineering Applications

The Fibrosis Across Organs Symposium: A Roadmap for Future Research Priorities

Epigenetic therapies in heart failure

HDAC5 catalytic activity suppresses cardiomyocyte oxidative stress and NRF2 target gene expression

A PDE3A Promoter Polymorphism Regulates cAMP-Induced Transcriptional Activity in Failing Human Myocardium

Metabolomics assessment reveals oxidative stress and altered energy production in the heart after ischemic acute kidney injury in mice

2018:

HDAC11 suppresses the thermogenic program of adipose tissue via BRD2

Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture

Epigenetics in Cardiac Fibrosis: Emphasis on Inflammation and Fibroblast Activation

Histone deacetylase governs diastolic dysfunction through a nongenomic mechanism​.

2017:

DUSP5 functions as a feedback regulator of TNFα-induced ERK1/2 dephosphorylation and inflammatory gene expression in adipocytes

Class I HDACs control a JIP1-dependent pathway for kinesin-microtubule binding in cardiomyocytes

p38α A Profibrotic Signaling Nexus

BRD4 inhibition for the treatment of pathological organ fibrosis.

Overlapping and Divergent Actions of Structurally Distinct Histone Deacetylase Inhibitors in Cardiac Fibroblasts.

Interleukin-37 suppresses the osteogenic responses of human aortic valve interstitial cells in vitro and alleviates valve lesions in mice. 

Tryptophan hydroxylase 1 Inhibition Impacts Pulmonary Vascular Remodeling in Two Rat Models of Pulmonary Hypertension. 

Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes.

2016:

The potential of targeting epigenetic regulators for the treatment of fibrotic cardiac diseases. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension. 

 

 

 

 

 

 

 

 

 

 

 

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Discovery of novel small molecule inhibitors of cardiac hypertrophy using high throughput, high content imaging.

 

 

 

 

 

 

 

 

 

 

 

Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation.​ 

 

 

 

 

 

 

 

Epigenetic regulation of cardiac fibrosis.​

2015:

High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling.

TNAP: a new player in cardiac fibrosis? Focus on "Tissue-nonspecific alkaline phosphatase as a target of sFRP2 in cardiac fibroblasts".

Emerging roles for histone deacetylases in pulmonary hypertension and right ventricular remodeling (2013 Grover Conference series).

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

Novel Interaction of Class IIb Histone Deacetylase 6 (HDAC6) with Class IIa HDAC9 Controls Gonadotropin Releasing Hormone (GnRH) Neuronal Cell Survival and Movement.

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.

2014:

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.