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Kenneth Walsh

Hematovascular Biology Center,
Robert M. Berne Cardiovascular Research Center,
Department of Biochemistry and Molecular Genetics,
Department of Cardiology,
Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center

University of Virginia School of Medicine

BIOGRAPHY

My laboratory broadly examines the molecular events that drive cardiovascular cell growth, differentiation and cell death. A major focus has been to elucidate mechanisms of inter-tissue communication and understand how these systems contribute to physiological versus pathological tissue growth in the cardiovascular system, particularly as they relate to systemic metabolic dysfunction and cardiovascular disease (CVD).

Our recent studies investigate how “clonal hematopoiesis” functions as a causal risk factor for cardio-metabolic diseases. Recent large exome sequencing studies in humans have shown that aging is frequently associated with the appearance of pre-leukemic, somatic mutations in the hematopoietic system that provide a competitive growth advantage to the mutant cell and allow its clonal expansion. These aberrant clonal events in the hematopoietic system have been found to be associated with greater risk of CVD. Using murine genetic models, our work suggests that there is a causal connection between clonal hematopoiesis and CVD, and we have elaborated aspects of the underlying mechanisms. The Walsh lab also collaborates with clinician-scientists to assess the status of clonal hematopoiesis in patient cohorts.

PUBLICATIONS

CRISPR-Mediated Gene Editing to Assess the Roles of Tet2 and Dnmt3a in Clonal Hematopoiesis and Cardiovascular Disease.

Circulation research 07, 2018 | Pubmed ID: 29728415

Relaxin Family Member Insulin-Like Peptide 6 Ameliorates Cardiac Fibrosis and Prevents Cardiac Remodeling in Murine Heart Failure Models.

Journal of the American Heart Association 06, 2018 | Pubmed ID: 29887522

Clonal Hematopoiesis and Its Impact on Cardiovascular Disease.

Circulation journal : official journal of the Japanese Circulation Society 12, 2018 | Pubmed ID: 30185689

Self-reactive CD4 IL-3 T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis.

The Journal of experimental medicine Feb, 2019 | Pubmed ID: 30670465

Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling.

Circulation May, 2019 | Pubmed ID: 30922063

Wnt5a-Mediated Neutrophil Recruitment Has an Obligatory Role in Pressure Overload-Induced Cardiac Dysfunction.

Circulation Aug, 2019 | Pubmed ID: 31170826

Cardiovascular Disease, Aging, and Clonal Hematopoiesis.

Annual review of pathology 01, 2020 | Pubmed ID: 31689371

-Mediated Clonal Hematopoiesis Accelerates Pathological Remodeling in Murine Heart Failure.

JACC. Basic to translational science Oct, 2019 | Pubmed ID: 31709318

Somatic mosaicism: implications for the cardiovascular system.

European heart journal 08, 2020 | Pubmed ID: 31876923

Genetics of age-related clonal hematopoiesis and atherosclerotic cardiovascular disease.

Current opinion in cardiology 05, 2020 | Pubmed ID: 32073406

Clonal Hematopoiesis: A New Step Linking Inflammation to Heart Failure.

JACC. Basic to translational science Feb, 2020 | Pubmed ID: 32140625

Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction.

JCI insight 03, 2020 | Pubmed ID: 32154790

Isolation of Highly Purified and Viable Retinal Endothelial Cells.

Journal of vascular research , 2021 | Pubmed ID: 33022674

TET2-Loss-of-Function-Driven Clonal Hematopoiesis Exacerbates Experimental Insulin Resistance in Aging and Obesity.

Cell reports 10, 2020 | Pubmed ID: 33113366

Clonal haematopoiesis and cardiovascular disease: how low can you go?

European heart journal 01, 2021 | Pubmed ID: 33313787

A Single-Cell Analysis of DNMT3A-Mediated Clonal Hematopoiesis in Heart Failure.

Circulation research Jan, 2021 | Pubmed ID: 33476205

Perivascular Adipose Tissue Inflammation in Ischemic Heart Disease.

Arteriosclerosis, thrombosis, and vascular biology 03, 2021 | Pubmed ID: 33504180

Importance of clonal hematopoiesis in heart failure.

Trends in cardiovascular medicine Apr, 2021 | Pubmed ID: 33892102

The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation.

Journal of the American Heart Association 07, 2021 | Pubmed ID: 34155901

Murine models of clonal hematopoiesis to assess mechanisms of cardiovascular disease.

Cardiovascular research Jun, 2021 | Pubmed ID: 34164655

TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response.

JCI insight Jul, 2021 | Pubmed ID: 34236050

The Cancer Therapy-Related Clonal Hematopoiesis Driver Gene Promotes Inflammation and Non-Ischemic Heart Failure in Mice.

Circulation research Sep, 2021 | Pubmed ID: 34315245

Hematopoietic JAK2-mediated clonal hematopoiesis: AIM2 understand mechanisms of atherogenesis.

The journal of cardiovascular aging , 2021 | Pubmed ID: 34396370

INSTITUTIONS

University of Virginia School of Medicine

JOVE ARTICLES

Lentiviral CRISPR/Cas9-Mediated Genome Editing for the Study of Hematopoietic Cells in Disease Models

Soichi Sano¹,

Ying Wang¹,

Megan A. Evans¹,

Yoshimitsu Yura¹,

Miho Sano¹,

Hayato Ogawa¹,

Keita Horitani¹,

Heather Doviak¹,

Kenneth Walsh¹

¹Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine

Immunology and Infection

Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis

Eunbee Park¹,

Megan A. Evans⁴,

Heather Doviak⁴,

Keita Horitani⁴,

Hayato Ogawa⁴,

Yoshimitsu Yura⁴,

Ying Wang²,

Soichi Sano^3,4,

Kenneth Walsh^1,4

¹Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine,

²Department of Cardiology, Xinqiao Hospital, Army Medical University,

³Department of Cardiology, Osaka City University Graduate School of Medicine,

⁴Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine

JoVE Core

Isolation of Murine Retinal Endothelial Cells for Next-Generation Sequencing

Nicholas W. Chavkin^1,2,

Shelby Cain¹,

Kenneth Walsh^2,3,4,

Karen K. Hirschi^1,2,4,5

¹Department of Cell Biology, University of Virginia School of Medicine,

²Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine,

³Department of Cardiology, University of Virginia School of Medicine,

⁴Hematovascular Biology Center, University of Virginia School of Medicine,

⁵Yale Cardiovascular Research Center, Yale University School of Medicine

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