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Role of therapy-related clonal hematopoiesis in anthracycline-induced cardiotoxicity

Description: NARRATIVE Significant associations have been noted between the aberrant expansion of blood cells with somatic mutations in TP53 or PPM1D and prior exposure to cancer treatments. These mutational events may increase the risk of cardiovascular disease, but causal data linking these mutations in cancer survivors with cardiovascular disease does not exist. The proposed experiments will experimentally examine whether amplification of TP53/PPM1D mutant clones in blood worsens cancer therapy-related damage to the heart, using an anthracycline drug as a test case.
Funding type: research
Funder scheme: R01
Start date: 2020-06-01
End date: 2025-04-30
Investigator: KENNETH WALSH
Institution: UNIVERSITY OF VIRGINIA
Field: Medicine
Funded outputs count: 38
Funder award ID: R01HL152174
OpenAlex ID: G1257266702
Clonal Hematopoiesis in Cancer and Cardiovascular Disease
2025 · Megan A. Evans, Kenneth Walsh · JACC CardioOncology · 12
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Mosaic loss of chromosome Y in blood is associated with male susceptibility for idiopathic pulmonary fibrosis
2025 · Josefin Bjurling, Nicholas W. Chavkin, et al. · Communications Medicine · 13
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Contributions of Noncardiac Organ–Heart Immune Crosstalk and Somatic Mosaicism to Heart Failure: Current Knowledge and Perspectives
2025 · Marinos Kallikourdis, Jesse D. Cochran, et al. · Circulation Research · 11
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Clonal Hematopoiesis Increases Hypertension and Sympathetic Activity and Is Reversed by Renal Denervation
2025 · Ariel H. Polizio, Lucila Marino, et al. · Hypertension · 4
Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke
2024 · Megan A. Evans, Nicholas W. Chavkin, et al. · Frontiers in Cellular Neuroscience · 4
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The emerging role of clonal haematopoiesis in the pathogenesis of dilated cardiomyopathy
2024 · Job A J Verdonschot, Jose J Fuster, et al. · European Heart Journal · 9
Experimental TET2 Clonal Hematopoiesis Predisposes to Renal Hypertension Through an Inflammasome-Mediated Mechanism
2024 · Ariel H. Polizio, Lucila Marino, et al. · Circulation Research · 32
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Mosaic Loss of the Y Chromosome Is Enriched in Patients With Wild-Type Transthyretin Cardiac Amyloidosis and Associated With Increased Mortality
2024 · Mark C. Thel, Jesse D. Cochran, et al. · Circulation Heart Failure · 8
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Clonal Hematopoiesis: The Emergent CVD Risk Factor
2024 · Jesse D. Cochran, Kenneth Walsh · Arteriosclerosis Thrombosis and Vascular Biology · 4
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Disruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure
2024 · Keita Horitani, Nicholas W. Chavkin, et al. · Nature Cardiovascular Research · 45
Clonal Hematopoiesis
2024 · Kenneth Walsh, Jesse D. Cochran, et al. · JACC Heart Failure
Regulators of clonal hematopoiesis and physiological consequences of this condition
2023 · Eunbee Park, Megan A. Evans, et al. · The Journal of Cardiovascular Aging · 4
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Clonal Hematopoiesis and Transcatheter Aortic Valve Replacement
2023 · Megan A. Evans, Kenneth Walsh · JACC Basic to Translational Science · 2
Obesity accelerates endothelial-to-mesenchymal transition in adipose tissues of mice and humans
2023 · Nicholas W. Chavkin, Tanvi Vippa, et al. · Frontiers in Cardiovascular Medicine · 14
Clonal Hematopoiesis in Clinical and Experimental Heart Failure With Preserved Ejection Fraction
2023 · Jesse D. Cochran, Yoshimitsu Yura, et al. · Circulation · 73
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Mosaic Loss of Y Chromosome in White Blood Cells: Its Impact on Men’s Health
2023 · Soichi Sano, Mark C. Thel, et al. · Physiology · 10
Clonal Hematopoiesis: From Macrovascular to Microvascular Disease
2023 · Jesse Cochran, Kenneth Walsh · Arteriosclerosis Thrombosis and Vascular Biology · 2
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Clonal hematopoiesis: the nonhereditary genetics of age-associated cardiovascular disease
2023 · Soichi Sano, Mark C. Thel, et al. · Current Opinion in Cardiology · 2
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Development of a Mouse Model of Hematopoietic Loss of Y Chromosome
2023 · Soichi Sano, Kenneth Walsh · BIO-PROTOCOL · 5
Experimental ASXL1 ‐Mediated Clonal Hematopoiesis Promotes Inflammation and Accelerates Heart Failure
2022 · Kyung‐Duk Min, Ariel H. Polizio, et al. · Journal of the American Heart Association · 45
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Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality
2022 · Soichi Sano, Keita Horitani, et al. · Science · 265
Therapy-Related Clonal Hematopoiesis
2022 · Yoshimitsu Yura, Jesse D. Cochran, et al. · Heart Failure Clinics · 14
Somatic Mosaicism in Biology and Disease
2021 · Hayato Ogawa, Keita Horitani, et al. · Annual Review of Physiology · 21
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The Cancer Therapy-Related Clonal Hematopoiesis Driver Gene Ppm1d Promotes Inflammation and Non-Ischemic Heart Failure in Mice
2021 · Yoshimitsu Yura, Emiri Miura-Yura, et al. · Circulation Research · 87
TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response
2021 · Soichi Sano, Ying Wang, et al. · JCI Insight · 81
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