Wai Hong Wilson Tang Laboratory

Research

Precision, Systems-Based Approach to Prevent Heart Failure and Cardiomyopathy

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, yet contemporary clinical care continues to rely on broad syndromic classifications that often obscure underlying biological heterogeneity. 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 lens, 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. At its core, the research program treats cardiovascular disease as a dynamic, multi-organ process shaped by genetic susceptibility, immune signaling, metabolic state, renal function, hemodynamics, and environmental exposure. Rather than studying these factors in isolation, the program integrates large systemwide patient cohorts with deep phenotyping—genetics, advanced cardiac imaging, electrophysiology, metabolomics, immune profiling, and tissue-based multiomics—to identify actionable biological states across disease initiation, progression, recovery, and relapse. This structure enables the transition from observational discovery to prospective randomized trials that directly inform clinical decision-making. The innovation of this research program lies in the integration of scale, depth, and clinical relevance. Large, diverse electronic health record-linked cohorts provide statistical power and generalizability, while curated human biospecimens and tissue resources and leverage mechanistic animal models to gain mechanistic insight. Advanced imaging, immune profiling, and multiomics are deployed with a clear purpose: to identify biological states that can be acted upon to improve cardiovascular health.   

Project 1: Genomics- and Biomarker-informed Cardiomyopathy Care

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.

Ongoing and Future Directions: Current efforts focus on scaling systematic identification of genotype-positive individuals and at-risk relatives through proactive outreach strategies and cascade screening. Ongoing studies integrate advanced cardiac magnetic resonance imaging, electrocardiogram-derived vectorcardiography, biomarkers, and multi-omic profiling to define early disease phenotypes and modifiers of penetrance. Future work will emphasize transcriptomic and molecular characterization of myocardial tissue linked to specific gene variants, with the goal of identifying actionable pathways for early intervention. This project aims to establish a precision prevention framework that enables risk stratification and targeted surveillance prior to overt disease manifestation.   

Project 2: Myocardial Recovery Biology and Immune Mechanisms

Established Contributions: This project is grounded in prior work defining neurohormonal, oxidative, and metabolic perturbations in heart failure, including identification of biomarkers and pathways associated with disease progression and clinical heterogeneity. 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.

Ongoing and Future Directions: Current work focuses on defining biological signatures of myocardial recovery using longitudinal biomarker trajectories, advanced imaging, and myocardial tissue profiling, including single-cell and single-nucleus RNA sequencing in patients undergoing mechanical circulatory support. Efforts are underway to distinguish durable recovery from compensated disease and to develop biomarker-based criteria to guide therapeutic de-escalation. In parallel, immune profiling studies are characterizing autoantibody-mediated signaling, complement activation, and host susceptibility factors such as HLA diversity. Future directions include identifying actionable immune endotypes and developing targeted immunomodulatory strategies, as well as investigating cardioprotective pathways such as neuregulin-1/ErbB signaling and SMYD1-mediated regulation.   

Project 3: Physiology-Guided Cardio-Renal Management

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. Prior work has also identified novel biomarkers and physiologic parameters associated with adverse cardio-renal outcomes, challenging traditional paradigms centered on arterial underfilling. 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.

Ongoing and Future Directions: Current studies apply integrated physiologic, biomarker, and electronic health record-based approaches to refine risk stratification and guide management in acute heart failure and cardiogenic shock. Ongoing work includes validation of congestion phenotypes, identification of patients at risk for diuretic resistance or renal injury, and application of physiologic modeling to guide decongestive strategies. Future directions include development of pragmatic clinical trials targeting congestion and renal protection, incorporation of advanced imaging and novel biomarkers to define mechanistic endotypes, and implementation of scalable, physiology-guided care pathways across health systems.   

Project 4: Diet, Gut Microbiome, and Metabolic Drivers of Heart Health

Established Contributions: This project is supported by pioneering work demonstrating that gut microbiome–derived metabolites, including trimethylamine N-oxide (TMAO) and related compounds, are mechanistically linked to cardiovascular and renal risk. These discoveries established a new paradigm connecting dietary exposures, microbial metabolism, and host cardiometabolic outcomes. Additional studies have identified a range of novel microbial-associated metabolites and characterized their associations with disease phenotypes, while early interventional work has demonstrated the feasibility of modulating these pathways through dietary strategies. Complementary investigations into metabolic dysfunction, including obesity, insulin resistance, and altered lipid and amino acid metabolism, have further defined the biological heterogeneity of heart failure, particularly heart failure with preserved ejection fraction.

Ongoing and Future Directions: Current efforts focus on integrating metabolomics, advanced metabolic imaging, and body composition analysis to define biologically distinct subtypes of metabolic heart failure and sarcopenia. Ongoing studies examine the relationship between microbial metabolites and clinical outcomes using large, well-phenotyped cohorts. Parallel pilot interventions are evaluating dietary and microbiome-targeted strategies to modulate these pathways. Future work will expand into precision nutrition approaches, targeted pharmacologic modulation of microbial metabolism, and incorporation of vascular and microcirculatory phenotyping to better understand systemic consequences of metabolic dysfunction. This project aims to translate mechanistic insights into scalable, non-traditional therapeutic strategies for cardiovascular disease. 

Selected Publications

View publications for Wai Hong Wilson Tang, MD
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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.