The Wolf Lab at the University of Virginia

Research

Publication Images with Captions

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Figure 1

Schematic of the αDKRC::RLTG mouse that restricts Cre recombinase expression to adult cardiomyocytes re-entering the cell cycle. Adult mice treated with tamoxifen activates Dre recombinase to excise a STOP cassettes and [1] initiate the expression of tdTomato and [2] prime an active Cre recombinase that is under the control of the cell cycle promoter, Ki67. [3] When a cardiomyocyte re-enters the cell cycle, as defined by the activation of Ki67, Cre recombinase is expressed and the tdTomato cassette is excised, causing the expression of eGFP.

(Bradley, L.A., Young, A., Li, H. Billcheck, H.O. and Wolf, M.J. (2021) Loss of Endogenously Cycling Adult Cardiomyocytes Worsens Myocardial Function. Circ Res. 128 (2):155-168. PMID: 33146578.)

Figure 2

αDKRC::RLTG mouse with immunofluorescent eGFP positive cardiomyocytes that re-entered the cell cycle after myocardial infarction.

Figure 3

Cardiomyocytes isolated from adult αDKRC::RLTG and αMHC-Cre::FUCCI2aR mice.

Figure 4

Immunofluorescent paired eGFP positive (green) in αDKRC::RLTG mice treated with Harmine, an inhibitor of DYRK1a, after myocardial infarction. Nuclei stained with DAPI.

(Young, A. Bradley, L.A., Farrar, E., Bilcheck, H.O., Tkachenko, S., Saucerman, J.J., Bekiranov, S., and Wolf, M.J. (2022) Inhibition of DYRK 1a Enhances Cardiomyocyte Cycling after Myocardial Infarction. Circ Res. Apr. PMID: 35369706.)

Figure 4a

Alternative immunohistochemical stain to reduce background, paired eGFP positive (red) in αDKRC::RLTG mice treated with Harmine, an inhibitor of DYRK1a, after myocardial infarction.

Figure 5

Composite and tile scanned imaging of immunofluorescent mouse hearts.

Figure 6

The “Snapshot” and “Summation” approaches to observing cycling events. “Detectable events” such as cycling cells occur after an injury or stimulus. The “Snapshot” view (Top) relies on observations, such as the expression of phospho-Histone-3, Aurora B, Ki67, or fluorescence-based reports like FUCCI, at a single time point. The "Summation” view (Bottom) relies on the incorporation and retention of a marker, such as BrdU, 3H-Thymidine, or EdU, reporting the integrative signal of “detectable events” over periods of time.

(Bradley, L.A., Young, A., Li, H. Billcheck, H.O. and Wolf, M.J. (2021) Loss of Endogenously Cycling Adult Cardiomyocytes Worsens Myocardial Function. Circ Res. 128 (2):155-168. PMID: 33146578.)

Figure 6a

Evolution of transgenic mouse technology to detect cycling cardiomyocytes.

Figure 7

A mouse heart after permanent ligation of proximal left anterior descending coronary artery, in myocardial infarction. (blue healthy viable tissue, unstained area is ischemic tissue).

Figure 8

Masson Trichrome (top) and Picro Sirius Red (bottom) stained mouse heart two weeks after 60 minutes of ischemia followed by reperfusion. Infarcted regions of fibrosis are denoted in blue (top) and red (bottom).

Figure 9

Mouse heart injected with microfil to opacity the coronary arteries in yellow (left) and optical coherence tomography (OCT) imaging of the vasculature (right). (Elizabeth Farrer, 2021 – Medical Student - University of Virginia School of Medicine).

Figure 10

Comparison of chronic occlusion (top left) and ischemia-reperfusion (top center) of the left anterior descending (LAD) artery. Schematic of 2,3,5-Triphenyltetrazolium chloride (TTC) staining after ischemia-reperfusion myocardial infarction depicting the scar (gray), area at risk (red) and viable area (blue). Representative sections of a heart after ischemia-reperfusion and stained using TTC.

List of Grants (past & present, public & private)

NIH R01 HL158718

Role:	Principal Investigator
Title:	DYRK1a as a therapeutic target to treat myocardial infarction
Date:	07/01/2021–7/31/2025

NIH R01 HL162925-01

Role:	Co-PI
Title:	Systems Pharmacology Model of Cardiac Hypertrophy
Date:	4/1/2022 - 3/31/2027

NIH R01 HL162872-01

Role:	Co-PI
Title:	Multiparametric MRI for the investigation of coronary microvascular disease
Date:	4/1/2022 - 3/31/2027

NIH 1U01AG070960-01

Role:	Collaborator
Title:	Machine learning-based multi-omics modeling and CRISPR/Cas9- mediated gene editing in elucidating molecular transducer of physical activity.

UVA-AstraZeneca Alliance

Role:	Principal Investigator
Title:	Investigating the enhancement of cardiomyocyte cycling by a modified mRNA in vivo after ischemia-reperfusion myocardial infarction
Date:	1/2021-12/2021

NIH R01 EB001763

Role:	Co-Investigator
Title:	MRI in Mouse Models of Heart Disease
Date:	09/30/17–06/30/20

NIH R01 HL1165810

Role:	Principal Investigator
Title:	Novel pathways modulating Raf-mediated cardiac hypertrophy
Date:	02/15/13-11/30/18

NIH K08-HL085072

Role:	Principal Investigator
Title:	Genetic modifiers of dilated cardiomyopathy in adult Drosophila
Date:	2007-2012

Commonwealth Health Research Board [CHRB] FY 2019/2020 Grant

Role:	Co-Principal Investigator
Title:	S Bioengineering of Cardiac Regeneration In Situ after Myocardial Infarction.
Date:	7/2019-6/2021

UVA-Engineering-in Medicine

Role:	Co-Principal Investigator
Title:	Mechanisms and therapy for coronary microvascular disease: role of iNOS and a heart-gut-microbiome
Date:	1/2021-12/2021

UVA-AstraZeneca Alliance

Role:	Co-Principle Investigator
Title:	Systems pharmacology of cardiomyocyte proliferation
Date:	8/2015-4/2020

UVA-Engineering-in Medicine

Role:	Co-Principle Investigator
Title:	In situ Bioengineering of Scar Formation after Myocardial Infarction
Date:	1/2018-12/2018

UVA-AstraZeneca Alliance

Role:	Principle Investigator
Title:	Receptor Antagonists in Mouse Models of Heart Failure
Date:	8/2015-8/2018

Amyloidosis Foundation

Role:	Principle Investigator
Title:	Modifiers of cardiac amyloid
Date:	1/2015-1/2017

Butler Award

Role:	Principle Investigator
Title:	Genetic variants of chemotherapy-induced cardiomyopathy
Date:	1/2014-1/2015

Mandel Foundation

Role:	Principle Investigator
Title:	Control of cardiomyocyte growth using novel genetic approaches in Drosophila
Date:	1/2014-1/2015

American Heart Association Beginning Grant-in-Aid

Role:	Principle Investigator
Title:	Suppressor screens of cardiac hypertrophy in flies to mammals
Date:	07/1/12-6/30/14

American Heart Association NCRP Innovative Research

Role:	Principle Investigator
Title:	Grant to identify genetic modifiers of sarcoglycan-mediated dilated cardiomyopathy
Date:	1/1/09-12/31/10

Robert J. Lefkowitz Innovation Research Award Grant

Role:	Principle Investigator
Date:	2009 and 2008

GlaxoSmithKline Research and Education Foundation Grant

Role:	Principle Investigator
Title:	Drosophila screens to identify new genes that cause dilated cardiomyopathies
Date:	7/1/07-6/30/09