Wai Hong Wilson Tang Lab | Cleveland Clinic Research

Principal Investigator

Wai Hong Wilson Tang, MD

Staff
Cardiovascular Medicine
Location: Cleveland Clinic Main Campus

Research

As a clinician-scientist, the goal of my research is to investigate mechanistic determinants of cardiovascular disease, particular in human heart failure and cardiomyopathy. One of the primary objectives is to understand the mechanisms to which genomic, immune, metabolic, and cellular processes promote disease progression, and the protective mechanisms that counteract these processes. The natural extension is to detect those at risk and intervene early, thereby preventing the development of heart failure and cardiomyopathy.

Biography

W. H. Wilson Tang, MD, is Research Director and staff cardiologist in the Section of Heart Failure and Cardiac Transplantation Medicine and Associate Section Head in the Section of Cardiovascular Genetics in the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at the Cleveland Clinic. Dr. Tang is Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (CWRU) and holder of the Robert C. Tarazi, MD Endowed Chair in Heart and Hypertension Research.

Dr. Tang is a clinician-scientist interested in clinical translational research, with joint appointments with the Department of Heart, Blood, and Kidney Research at Cleveland Clinic Research. He leads the Cleveland Heart and Metabolic Prevention Study to investigate novel mechanisms in the development of heart diseases and co-leads the Cleveland GeneBank and BioBank Studies. Dr. Tang also has leadership role in the CWRU's Clinical and Translational Sciences Collaborative, overseeing the Resources and Services Module and the Clinical Research Unit at the Cleveland Clinic. Dr. Tang’s current research interests include the role of counter-regulatory mechanisms in the development and progression of heart failure, integrative genomics and epigenetics in cardiomyopathies, and metabolomics in heart-kidney physiology.

Dr. Tang has authored over 1,000 published peer-reviewed manuscripts in medical and scientific journals and chapters in medical textbooks (Scopus h-index 128). He currently serves in the Editorial Boards for Journal of the American College of Cardiology (JACC) Heart Failure, JACC Cardio-Oncology, Circulation Heart Failure, and American Heart Journal. He previously served as member of Board of Directors for Heart Failure Society of America (HFSA), and was elected as member of the American Society of Clinical Investigation in 2013 for his contributions to physiologic and mechanistic understanding of cardio-renal syndromes, as well as the Association of American Physicians in 2018 for invetigating the contributing role of diet and microbiome in human heart and kidney diseases. He has received the American College of Cardiology's 2022 Distinguished Scientist Award in the Basic Domain and the HFSA 2025 Pioneer Award for his scientific contributions to the field of heart failure and cardiomyopathy.

Education & Professional Highlights

Education & Fellowships

Fellowship - Cleveland Clinic
Advanced Heart Failure and Transplant Cardiology
Cleveland, OH USA
2004

Fellowship - Cleveland Clinic
Cardiovascular Medicine
Cleveland, OH USA
2003

Fellowship - Stanford University School of Medicine
Postdoctoral research fellowship
Stanford, CA USA
2000

Residency - Stanford University Medical Center
Stanford, CA USA
1999

Internship - Stanford University Medical Center
Internal Medicine
Palo Alto, CA USA
1997

Medical Education - Harvard Medical School
Boston, MA USA
1996

Undergraduate - Jesus College, Cambridge University
Natural Sciences (Part II Tripos)
Cambridge, United Kingdom
1992

Undergraduate - Brown University
Neural Sciences
Providence, RI USA
1992

Professional Highlights

Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
Robert C. Tarazi, MD, Endowed Chair in Heart and Hypertension Research
Lead, NIH/NCATS Clinical and Translational Sciences Collaborative Resources and Services Module, Case Western Reserve University
Research Director, Section of Heart Failure and Cardiac Transplantation Medicine, Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at the Cleveland Clinic
Medical Director, Clinical Research Unit, Cleveland Clinic Research, Cleveland Clinic
Medical Director, Center for Cardiovascular Diagnostics and Prevention, Department of Heart, Blood and Kidney Research, Cleveland Clinic Research, Cleveland Clinic

Certifications

Internal Medicine
Internal Medicine - Cardiovascular Disease
Internal Medicine - Advanced Heart Failure and Transplant Cardiology

Awards & Honors

Fellow, American College of Cardiology, 2005
Fellow, American Heart Association, 2006
Elected member, American Society of Clinical Investigation, 2013
2016 Maria and Sam Miller Professional Excellence Award for Scientific Achievement in Clinical Research
Fellow, Heart Failure Society of America, 2017
Elected member, Association of American Physicians, 2018
Sones/Favaloro Award Excellence in Research, 2019, 2025, 2026
Cleveland Clinic Lerner College of Medicine Excellence in Research Education Award, 2025
Heart Failure Society of America Pioneer Award, 2025

Innovations & Patents

Research funding from National Institutes of Health (2010-present)

Memberships

American College of Cardiology
American Heart Association
Heart Failure Society of America
International Society of Heart and Lung Transplantation
American Society of Clinical Investigations
Association of American Physicians

Research

Human Translational Myocardial Disease Research Program

Heart failure and cardiomyopathy are biologically diverse diseases, yet traditional disease labels often obscure underlying biological diversity. Patients with similar clinical diagnoses frequently follow markedly different trajectories—some develop disease early due to inherited risk, others progress despite guideline-directed therapy, while a subset demonstrate myocardial recovery or resilience despite high-risk profiles. These observations highlight a fundamental gap in our understanding of cardiovascular disease biology and underscore the need for more precise, mechanism-based approaches to care.

Dr. Tang’s research program is designed to address this gap by redefining cardiovascular disease through a precision, systems-based approachs, with the explicit goal of translating biological insight into earlier detection, improved risk stratification, and mechanism-guided intervention. The overall objective is to gain mechanistic insights into development and progression of heart failure and cardiomyopathy and translate into safe and efficacious precision therapeutics. Patients with similar clinical diagnoses often have different underlying mechanisms, disease trajectories, and responses to therapy. Our research seeks to understand these biological differences and translate that knowledge into more effective strategies for diagnosis, risk stratification, and treatment. Our laboratory combines prospective clinical studies, advanced cardiovascular phenotyping, molecular biology, genomics, biomarker discovery, and translational research to define the mechanisms that drive myocardial disease. By connecting patients, biospecimens, advanced molecular technologies, and pragmatic clinical trials within a learning health system, we aim to accelerate the development of precision cardiovascular therapies that improve outcomes for patients with heart failure, cardiomyopathy, and related diseases.

Our Vision: To build a comprehensive Human Translational Myocardial Disease Research Program that integrates clinical care, biological discovery, and therapeutic innovation to better understand the biological determinants of myocardial vulnerability, adaptation, and recovery.

Program 1. Cardio-Immunology & Myocardial Recovery

Scientific Question: How do immune mechanisms determine myocardial injury, recovery, and progression?

Background: Cardiovascular diseases are increasingly recognized as disorders of immune regulation, where inflammation can contribute to both tissue repair and disease progression. Our research investigates how the immune system influences myocardial injury, healing, and long-term recovery. We study both harmful and protective immune responses to identify biological markers that can predict recovery and discover new therapeutic targets. By understanding the immune mechanisms that distinguish patients who recover from those who continue to decline, we hope to develop more personalized treatment strategies and novel immunotherapies that improve heart function and prevent disease progression.

Established Contributions: Longitudinal cohort studies have characterized biomarker trajectories (such as natriuretic peptides) and highlighted variability in clinical outcomes, including subsets of patients demonstrating myocardial recovery. In parallel, foundational discoveries in immune-mediated mechanisms—including the identification of functional autoantibodies and dysregulated inflammatory pathways—have provided early evidence that immune signaling contributes to myocardial injury and may also confer cardioprotective effects under specific conditions.

Clinical Translation: We conduct prospective studies in patients with heart failure to develop biomarker-guided approaches for monitoring myocardial recovery, predicting relapse, and identifying patients most likely to benefit from emerging immunomodulatory therapies. Current clinical focus includes: 1) Heart failure with recovered ejection fraction clinical trajectories; 2) Biomarker-guided endotyping and management strategies; and 3) Immune endotyping and longitudinal clinical phenotyping.

Mechanistic Discovery: Using advanced immune profiling and molecular assays, we investigate how innate and adaptive immune pathways contribute to myocardial injury and repair, with particular interest in autoantibodies, macrophage biology, complement activation, and targeted immunotherapy. Representative research work includes: 1) Functional β1-adrenergic receptor autoantibodies; 2) Innate immune and complement activation; 3) Immune biomarker discovery and therapeutic target identification.

Program 2. Cardio-Kidney-Metabolic Axis

Scientific Question: How do systemic metabolic, renal, and nutritional factors influence myocardial health and disease progression?

Background: Heart disease extends beyond the myocardium itself. Interactions among metabolism, kidney function, nutrition, circulating metabolites, and protein homeostasis play critical roles in determining disease progression and therapeutic response. Our research seeks to define these interconnected pathways and identify biological signatures that can guide earlier diagnosis and more individualized treatment. By combining advanced imaging, biomarker discovery, and clinical studies of nutrition and metabolic health, we aim to develop precision approaches that improve resilience, slow disease progression, and reduce the burden of heart failure.

Established Contributions: This project builds on seminal contributions that have redefined the pathophysiology of cardio-renal syndrome, including the recognition of venous congestion and intra-abdominal pressure as key determinants of renal dysfunction in heart failure. Leadership in multicenter clinical trials and national consortia has further contributed to advancing understanding of acute heart failure, congestion, and renal injury, and has informed clinical guidelines and scientific statements in this field. Pioneering work demonstrating that gut microbiome–derived metabolites, including trimethylamine N-oxide (TMAO) and phenylacetylglutamine (PAGln), are mechanistically linked to heart and kidney risks and disease progression, and feasibility of modulating these pathways through dietary strategies in preclinical models. Complementary investigations into metabolic dysfunction, including obesity, insulin resistance, and altered lipid and amino acid metabolism, have further defined the biological heterogeneity particularly in heart failure with preserved ejection fraction (HFpEF).

Clinical Translation: We combine advanced imaging, biomarker profiling, and longitudinal clinical studies to define biologically distinct forms of heart failure and cardiorenal disease while evaluating targeted dietary, metabolic, and pharmacologic interventions. Current clinical focus includes: 1) Cardiometabolic HFpEF phenotyping; 2) Cardio-renal trajectory modeling; 3) Precision nutrition and dietary intervention studies.

Mechanistic Discovery: Our laboratory investigates the biological pathways linking metabolism, kidney dysfunction, oxidative stress, microbial metabolites, and protein homeostasis to myocardial remodeling and disease progression. Representative research work includes: 1) Fibrosis biology and metabolic remodeling; 2) Transthyretin destabilization and proteostasis; 3) Gut microbial dietary metabolites and cardiovascular health.

Program 3. Cardio-Genomics & Molecular Regulation

Scientific Question: Why do individuals with similar genetic predisposition develop markedly different forms of myocardial disease, and can these molecular mechanisms be targeted to prevent disease progression?

Background: Inherited cardiomyopathies provide a unique window into the biological mechanisms that determine myocardial susceptibility. Although pathogenic genetic variants increase the risk of disease, they do not fully explain why some individuals remain asymptomatic for decades while others develop early heart failure, malignant arrhythmias, or progressive myocardial fibrosis. Our research seeks to identify the molecular pathways that influence disease expression, uncover new therapeutic targets, and develop strategies for earlier intervention before irreversible myocardial injury occurs.

Established Contributions: This project builds on extensive experience in clinical and translational genomics, including leadership roles in large biorepositories and national consortia that have defined genetic determinants of cardiovascular disease. Prior work has contributed to the development of genotype–phenotype correlations in cardiomyopathies and implementation of clinical genomics programs, including integration of genetic testing into cardiovascular care. The program has also established foundational infrastructure for identifying patients with inherited cardiomyopathies and conducting clinical and genetic screening, supported by systemwide registries and biobanking efforts. Early work integrating electrophysiologic and imaging phenotypes with molecular data has demonstrated the feasibility of linking genetic variation to clinically meaningful phenotypes.

Clinical Translation: Through a comprehensive inherited cardiovascular disease program, we integrate genetic testing, advanced cardiovascular imaging, biomarkers, electrophysiologic assessment, to understand the earliest stages of disease development and improve risk stratification for early interventions. Current clinical focus includes: 1) Longitudinal phenotyping of genetic cardiomyopathies; 2) Early disease detection of subclinical phenotypes; 3) Epigenetic determinants of disease susceptibility.

Mechanistic Discovery: By integrating transcriptomics, functional genomics, and molecular biology, we seek to understand how regulatory pathways influence myocardial adaptation, remodeling, and progression across both inherited and acquired forms of cardiomyopathy. These studies provide a foundation for developing novel therapeutic approaches toward mechanism-based cardiovascular therapies. Representative research work includes: 1) Functional genomics with multiomics insights; 2) LMNA cardiomyopathy molecular phenotyping; 3) RNA-binding proteins and epigenetic regulation of myocardial remodeling.

Our Team

Publications

Selected Publications

View publications for Wai Hong Wilson Tang, MD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)

Tang WH, Girod JP, Lee MJ, Starling RC, Young JB, Van Lente F, Francis GS. Plasma B-type natriuretic peptide levels in ambulatory patients with established chronic symptomatic systolic heart failure. Circulation. 2003; 108(24):2964-6.

Tang WH, Tong W, Troughton RW, Martin MG, Shrestha K, Borowski A, Jasper S, Hazen SL, Klein AL. Prognostic value and echocardiographic determinants of plasma myeloperoxidase levels in chronic heart failure. J Am Coll Cardiol. 2007; 49(24):2364-70.

Mullens W, Abrahams Z, Skouri HN, Francis GS, Taylor DO, Starling RC, Paganini E, Tang WH. Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function? J Am Coll Cardiol. 2008; 51(3):300-6.

Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, Young JB, Tang WHW. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol. 2009; 53(7):589-596.

Tang WH, Francis GS, Morrow DA, Newby LK, Cannon CP, Jesse RL, Storrow AB, Christenson RH, Apple FS, Ravkilde J, Wu AH; National Academy of Clinical Biochemistry Laboratory Medicine. National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: Clinical utilization of cardiac biomarker testing in heart failure. Circulation. 2007; 116(5):e99-109.

Tang WH, Wang Z, Cho L, Brennan DM, Hazen SL. Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk. J Am Coll Cardiol. 2009; 53(22):2061-7.

Tang WH, Hartiala J, Fan Y, Wu Y, Stewart AF, Erdmann J, Kathiresan S; CARDIoGRAM Consortium; Roberts R, McPherson R, Allayee H, Hazen SL. Clinical and genetic association of serum paraoxonase and arylesterase activities with cardiovascular risk. Arterioscler Thromb Vasc Biol. 2012; 32(11):2803-12.

Tang WH, Wu Y, Hartiala J, Fan Y, Stewart AF, Roberts R, McPherson R, Fox PL, Allayee H, Hazen SL. Clinical and genetic association of serum ceruloplasmin with cardiovascular risk. Arterioscler Thromb Vasc Biol. 2012; 32(2):516-22.

Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013; 368(17):1575-84.

Singh D, Shrestha K, Testani JM, Verbrugge FH, Dupont M, Mullens W, Tang WH. Insufficient natriuretic response to continuous intravenous furosemide is associated with poor long-term outcomes in acute decompensated heart failure. J Card Fail. 2014; 20(6):392-9.

Tang WH, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM, Wu Y, Hazen SL. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014; 64(18):1908-14.

Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, Li XS, Levison BS, Hazen SL. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015; 116(3):448-55.

Nagatomo Y, McNamara DM, Alexis JD, Cooper LT, Dec GW, Pauly DF, Sheppard R, Starling RC, Tang WH; IMAC-2 Investigators. Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β1-Adrenergic Receptors. J Am Coll Cardiol. 2017; 69(8):968-977.

Li W, Kennedy D, Shao Z, Wang X, Kamdar AK, Weber M, Mislick K, Kiefer K, Morales R, Agatisa-Boyle B, Shih DM, Reddy ST, Moravec CS, Tang WHW. Paraoxonase 2 prevents the development of heart failure. Free Radic Biol Med. 2018; 121:117-126.

Liu CF, Abnousi A, Bazeley P, Ni Y, Morley M, Moravec CS, Hu M, Tang WHW. Global analysis of histone modifications and long-range chromatin interactions revealed the differential cistrome changes and novel transcriptional players in human dilated cardiomyopathy. J Mol Cell Cardiol. 2020; 145:30-42

Mohan ML, Nagatomo Y, Saha PP, Mukherjee SD, Engelman T, Morales R, Hazen SL, Tang WHW, Naga Prasad SV. The IgG3 subclass of β1-adrenergic receptor autoantibodies is an endogenous biaser of β1AR signaling. Mol Biol Cell. 2021; 32(7):622-633.

Liu CF, Ni Y, Moravec CS, Morley M, Ashley EA, Cappola TP, Margulies KB, Tang WHW. Whole-Transcriptome Profiling of Human Heart Tissues Reveals the Potential Novel Players and Regulatory Networks in Different Cardiomyopathy Subtypes of Heart Failure. Circ Genom Precis Med. 2021; 14(1):e003142.

Tang WHW, Nemet I, Li XS, Wu Y, Haghikia A, Witkowski M, Koeth RA, Demuth I, König M, Steinhagen-Thiessen E, Bäckhed F, Fischbach MA, Deb A, Landmesser U, Hazen SL. Prognostic value of gut microbe-generated metabolite phenylacetylglutamine in patients with heart failure. Eur J Heart Fail. 2024; 26(2):233-241.

Kodur N, Gunsalus P, Milinovich A, Dalton JE, Tang WHW. Prognostic Value of Natriuretic Peptide Levels in Heart Failure With Recovered Ejection Fraction. Circ Heart Fail. 2025; 18(11):e013386.

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Wai Hong Wilson Tang Laboratory

Wai Hong Wilson Tang Laboratory

Principal Investigator

Wai Hong Wilson Tang, MD

Research

Biography

Education & Professional Highlights

Research

Research

Human Translational Myocardial Disease Research Program

Program 1. Cardio-Immunology & Myocardial Recovery

Program 2. Cardio-Kidney-Metabolic Axis

Program 3. Cardio-Genomics & Molecular Regulation

Our Team

Our Team

Publications

Selected Publications

Research News

Research News