Jonathan G. Seidman

Heart Failure / Cardiomyopathy

Harvard University

About

Jonathan G. Seidman works in Heart Failure / Cardiomyopathy affiliated with Harvard University.

Jonathan G. Seidman, Ph.D., is the Henrietta B. and Frederick H. Bugher Foundation Professor of Genetics at Harvard Medical School. He co-directs the Seidman Laboratory with Christine E. Seidman, identifying gene mutations that cause hypertrophic and dilated cardiomyopathy and congenital heart disease. He joined the Harvard Medical School faculty in 1981 and was a Howard Hughes Medical Institute investigator from 1988 to 2005.

Research focus

Genetics of hypertrophic cardiomyopathyTitin truncations and dilated cardiomyopathyCongenital heart defect geneticsSarcomere protein mutationsiPSC and mouse models of inherited cardiomyopathy

Impact

532 pubs · 95,544 cites · h-index 132

Training

BA, Biochemistry
Harvard University
1971
PhD, Molecular Biology
University of Wisconsin
1975

Affiliations

Work Experience

Henrietta B. and Frederick H. Bugher Foundation Professor of Genetics

Harvard Medical School · 1981 - Present

Investigator

Howard Hughes Medical Institute · 1988 - 2005

Postdoctoral researcher

National Institutes of Health · 1975 - 1981

Publications

Kevin Koch

Cardiac electrophysiology and arrhythmias · Edgewise Therapeutics (United States)

cardiac myosin inhibitors such as Camzyos and aficamten may be on-off switches for myosin, while EDG-7500, which is a cardiac sarcomere modulator, is more about controlling the rate of interaction. With the company's more controlled approach, there may be fewer side effects

Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator

JCI InsightEmter et al.Sep 2026

Robert Roberts

Cardiologist and CEO, Ottawa Heart Institute · University of Ottawa Heart Institute

10d

The clinical picture was interesting, manifesting an age-dependent bimodal whereby individuals developing DCM in childhood had severe disease (often ending in death), whereas those who developed the phenotype in adulthood tended to have a less severe form of disease. Previously, several mutations in tropomyosin have been identified to be associated with HCM rather than DCM.

Familial Dilated Cardiomyopathy Caused by an Alpha-Tropomyosin Mutation

Journal of the American College of CardiologyLakdawala et al.Jan 2010

JACC Basic to Translational ScienceGreen et al.preclinical

Yucatan minipigs with a heterozygous knockin of the human MYH7 R403Q variant exhibited left ventricular hypertrophy, increased interstitial fibrosis, myocyte disarray, and early hypercontractility, effectively replicating human hypertrophic cardiomyopathy.

A novel transgenic porcine model of MYH7 R403Q accurately recapitulates the structural, physiological, and multi-omic characteristics of human hypertrophic cardiomyopathy, offering a valuable platform for translational studies.

Yuri Kim

Heart Failure / Cardiomyopathy · Chonnam National University

This was interesting, because cardiomyopathies are usually thought of as diseases of heart muscle cells only.

The molecular landscape of hypertrophic cardiomyopathy across disease stages and genotypes

Science Translational MedicineAdami et al.Sep 2026

Christine Seidman

Heart Failure / Cardiomyopathy · Brigham and Women's Hospital

2mo

Only this level of resolution allows us to see that cardiomyopathies do not uniformly trigger the same pathological pathways. Rather, different mutations evoked specific and some shared responses that lead to heart failure. These genotype-specific responses point to the importance of genotyping.

Pathogenic variants damage cell compositions and single cell transcription in cardiomyopathies

European Heart JournalReichart et al.Oct 2022

JACCFatkin et al.Original Research

Precision medicine and genomic information offer opportunities for variant-targeted therapies in dilated cardiomyopathy, though interpreting variants of unknown significance remains a key challenge.

May support precision medicine in dilated cardiomyopathy; leaves open confirmation in larger trials before practice change.

Proceedings of the National Academy of SciencesDutta et al.cohort

MYH7 interface variants linked to ~92% higher rate of HCM diagnosis vs non-interface variants.

May support refined HCM risk stratification for MYH7 carriers; extends structural interface mapping to outcomes but leaves prospective validation open.

JCI InsightVu et al.Original Research

Apelin analog treatment reverses severe pulmonary arterial hypertension and right ventricular heart failure

Reveals apelin analog reverses pulmonary arterial hypertension and right ventricular failure, indicating its therapeutic potential.

JACC Basic to Translational SciencePfaller et al.preclinical

R-pioglitazone reverses disease progression in murine HCM, reducing interstitial fibrosis by ~95%.

R-pioglitazone demonstrates potential as a disease-modifying therapy for hypertrophic cardiomyopathy by reversing fibrosis and hypertrophy in a murine model.

CirculationNeyazi et al.Animal Study

Cardiac sarcoidosis features intracardiac autoimmunity with clonally expanded B cells targeting desmosomal periplakin.

Should not yet change cardiac sarcoidosis management; leaves open whether targeting periplakin autoantibodies improves outcomes.

Dutta et al.Original Research

Thick filament molecular interfaces play a critical role in pathogenesis of hypertrophic and dilated cardiomyopathy

Analysis reveals critical molecular interfaces in hypertrophic and dilated cardiomyopathy variants, suggesting implications for patient risk stratification.

Circulation ResearchXiao et al.preclinical

A genetically barcoded multiplex platform using 16 iPSC lines successfully identified that GATA4 and WAC inactivation, along with a subset of CHD variants, altered cardiac differentiation.

A novel genetically barcoded iPSC platform enables scalable and reliable functional assessment of variants of unknown significance in congenital heart disease.

ScienceHuang et al.Original Research

Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations

Analysis reveals that mtDNA mutations impair resilience to kidney injuries, indicating chronic kidney disease risk.

Nature Cardiovascular ResearchBerg et al.Original Research

Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development

This research demonstrates that endocardial cilia and blood flow influence EndoMT in early valve development, suggesting new pathways for addressing congenital heart disease.

BMC Medical GenomicsSuresh et al.case-control

Congenital heart disease is linked to ~54% greater clustering of de novo tandem repeat variants.

Should not change CHD genetic evaluation; extends de novo variant spectrum for hypothesis-generating research.

Nature CommunicationsWatkins et al.cohort

Damaging de novo chromatin genetic variants increased the relative risk of mortality 1.8-fold, cardiac arrest 1.7-fold, and prolonged ventilation 1.6-fold.

May flag high-risk congenital cardiac surgery patients for closer monitoring; leaves open whether genetic screening improves outcomes.

Science Translational MedicineWang et al.preclinical

Adoptive transfer of splenic Treg cells reduced cardiac fibrosis and improved systolic dysfunction, and low-dose IL-2/c ameliorated cardiac fibrosis and reduced macrophage infiltration in Actc1E99K mice.

Suggests a novel immunomodulatory target for hypertrophic cardiomyopathy; leaves open whether Treg expansion or transfer.

Circulation ResearchPepin et al.preclinical

Intact NNT in mice promoted worse diastolic dysfunction after HFD+L-NAME feeding compared to NNT loss-of-function.

NNT modulation warrants preclinical testing in HFpEF; hypothesis-generating for mitochondrial targets with no clinical implications yet.

EHJBaka et al.preclinical

Empagliflozin treatment resulted in a significant reduction in left ventricular hypertrophy and myocardial fibrosis, improved left ventricular diastolic function and contractile reserve, and enhanced mitochondrial ATP synthesis.

Supports further investigation in HCM; leaves open clinical translation from this murine model.

NatureRuan et al.Original Research

Targeting the circadian BMAL1-HIF2A-AREG pathway reduces myocardial injury when timed to its circadian phase.

as a rhythmic target of the BMAL1-HIF2A complex, critical for regulating daytime variations of myocardial injury. Pharmacologically targeting the BMAL1-HIF2A-AREG pathway provides cardioprotection, with maximum efficacy when aligned with the pathway's circadian phase. These findings identify a mechanism governing circadian variations of myocardial injury and highlight the therapeutic potential of clock-based pharmacological interventions for treating ischaemic heart disease.

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