About

My aspiration to become a physician-scientist stems from my desire to care for patients with cardiovascular diseases and my passion for biomedical research. I have frequently encountered patients with end-stage heart failure who were not candidates for heart transplantation and continued to decline clinically despite receiving standard medical therapies. The physical and emotional toll on these patients and their families, along with the significant socioeconomic burden, was immense. These experiences inspired me to study the mechanisms of heart failure, with the goal of identifying new therapeutic targets and interventions. As a physician and junior faculty in the Division of Cardiology and the Mitochondrial Metabolism Center, I am committed to translating my research findings into clinical applications that improve patient outcomes, while mentoring the next generation of physician-scientists to advance the field of cardiovascular medicine.

The lab’s research focuses on the immunometabolic disturbances associated with heart failure and potential therapeutic interventions to reverse these changes. Specifically, we are investigating the role of extracellular mitochondria in mediating inflammation in chronic heart failure. Mitochondria, traditionally known as the powerhouse of the cell, can trigger an immune response when present outside the cell due to their shared evolutionary origins with bacteria. In addition to being passively released during massive tissue death, such as myocardial infarction, mitochondria are also secreted from cells within vesicles (MitoEV) or as free mitochondria. This so-called “active release of mitochondria” is a dynamic, regulated process involving molecular triggers, the state of intracellular mitochondria, and quality control mechanisms such as mitophagy.

Boosting nicotinamide adenine dinucleotide (NAD+) through precursors like nicotinamide riboside (NR) has emerged as a promising therapeutic strategy for chronic conditions such as heart failure. Research indicates that increasing NAD+ levels can improve mitochondrial function and reduce systemic inflammation, serving as a potential therapeutic target for extracellular mitochondria-mediated sterile inflammation.

Our working model of heart failure inflammation proposes that circulating mitochondrial DNA (mtDNA) activates TLR9 in monocytes, leading to mitochondrial injury. The injured mitochondria overwhelm the mitophagy machinery and are released as MitoEVs and free mitochondria, amplifying the inflammatory signal in an autocrine/paracrine manner. Additionally, MitoEVs may travel to distant tissues, contributing to organ-level inflammation. Boosting NAD helps protect against mtDNA-induced mitochondrial dysfunction, reduces MitoEV release, and alleviates inflammation.

Honors & Awards

2003          Graduation with Distinction in General Scholarship (Cum Laude), University of California, Berkeley
2004          NIH Funding Position for the Medical Scientist Training Program at University of California, Irvine – given to top student of every MSTP class
2005          Dr. Grace Bell Award for Molecular Biology, UC Irvine
2006          NSF Integrative Graduate Education and Research Traineeship (IGERT). LifeChips, UC Irvine – Full Scholarship for 2 years.
2009          Orange County Achievement Rewards for College Scientist (ARCS) Foundation Scholarship
2012          Jane Hill Cancer Research Scholarship
2012          External Rotation Scholarship, UC Irvine School of Medicine
2013          Graduation with Distinction in Research, UC Irvine School of Medicine
2019          Bruce-Laughlin Cardiovascular Research Fellowship (2019-2020) – University of Washington
2020          Grace Marie Kaylor Endowed Award (2020) – Division of Cardiology, University of Washington
2022          UW Department of Anesthesia Academic Evening Poster Competition: 3^rd Place
2024          AHA BCVS ACRE-ACS Symposium Oral Presentation Junior Faculty Award: 2^nd  Place

Education

Wang DD, Naumova AV, Isquith D, Sapp J, Huynh KA, Tucker I, Balu N, Voronyuk A, Chu B, Ordovas K, Maynard C, Tian R, Zhao XQ, Kim F.Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure. Cardiovasc Diabetol. 2024 Jun 7;23(1):197. doi: 10.1186/s12933-024-02294-z. PubMed PMID: 38849829; PubMed Central PMCID: PMC11161924.

Wang DD, Airhart SE, Zhou B, Shireman LM, Jiang S, Melendez Rodriguez C, Kirkpatrick JN, Shen DD, Tian R, O’Brien KD. Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. JACC Basic Transl Sci. 2022 Dec;7(12):1183-1196. doi: 10.1016/j.jacbts.2022.06.012. eCollection 2022 Dec. PubMed PMID: 36644285; PubMed Central PMCID: PMC9831861.

Zhou B, Wang DD, Qiu Y, Airhart S, Liu Y, Stempien-Otero A, O’Brien KD, Tian R. Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure. J Clin Invest. 2020 Nov 2;130(11):6054-6063. doi: 10.1172/JCI138538. PubMed PMID: 32790648; PubMed Central PMCID: PMC7598081.