Victor J. Dzau's research while affiliated with Washington DC VA Medical Center and other places

Publications (716)

Article
Policy Points • Hospital-at-Home (HaH) is a home-based alternative for acute care that has expanded significantly under COVID-19 regulatory flexibilities. • The post-pandemic policy agenda for HaH will require consideration of multistakeholder perspectives, including patient, caregiver, provider, clinical operations, technology, equity, legal, qua...
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MicroRNA-based cellular fate reprogramming offers an opportunity to investigate the mechanisms of long-term gene silencing. To further understand how genes are silenced in a tissue-specific manner, we leveraged our miRNA-based method of reprogramming fibroblasts into cardiomyocytes. Through screening approaches, we identified three proteins which w...
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As the number of physician-scientists continues to decline, action must be taken to support them as they embark on their careers.
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The COVID-19 pandemic created significant challenges for academic health systems (AHSs) across their tripartite mission of providing clinical care, conducting research, and educating learners. Despite these challenges, AHSs played an invaluable role in responding to the pandemic. Clinicians worked tirelessly to care for patients, and institutions q...
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We, and others, have demonstrated that directly reprogramming scar fibroblasts into new cardiomyocytes improves cardiac function in the infarcted heart. A major challenge is the specific delivery of reprogramming factors to cardiac fibroblasts in vivo. Currently, reprogramming factors are delivered into the heart by viruses which are often poor del...
Article
There is considerable interest in regenerating the injured heart by reprogramming resident fibroblasts into new functional cardiomyocytes. Cardiac reprogramming has been achieved via transcription factors or miRNAs. Transcription factor combinations appear to be species-specific as evidenced by the fact that combinations of transcription factors wh...
Article
We have discovered that innate immunity plays an important role in the reprogramming of fibroblasts into cardiomyocytes. Previously, we have focused on the role of the TLR3-NFkB pathway. We have now found evidence for an alternative Rig-1:YY1 pathway. Specific Rig-1 agonists such as 3p-hpRNA were found to enhance the efficacy of cardiac reprogrammi...
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This paper aims to provide an important update on the recent preclinical and clinical trials using cell therapy strategies and engineered heart tissues for the treatment of postinfarction left ventricular remodeling and heart failure. In addition to the authors’ own works and opinions on the roadblocks of the field, they discuss novel approaches fo...
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The emergence of new cell and gene-based therapies (CGTs) utilizing innovative technologies has recently intensified. Long-standing efforts in publicly funded biomedical research have resulted in breakthrough therapeutic approaches for patients with devastating and life-threatening diseases. Transformative gene-based therapeutic tools include human...
Article
Significance Cardiac injury in mammals is associated with a significant and irreversible loss of heart muscle cells (cardiomyocytes). The loss of cardiomyocytes eventually causes heart failure, leading to organ replacement or death. The importance of this study is that we have made the discovery that new cardiomyocytes can be regenerated in the hea...
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Audio Interview Interview with Dr. J. Michael McGinnis on supporting the evolution of a learning health system. (19:56)Download Recognizing that technological and methodologic advances could improve on the pace, generalizability, and costs of innovation in health and medicine, the National Academy of Medicine has helped steward the evolution of a c...
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The health care system in the US has faced many challenges in its history, from the high cost of health care to worse outcomes for racial and ethnic minority populations and a lack of robust public health infrastructure. As entrenched as these problems have been, they have been illuminated and exacerbated by COVID-19, which has served as a potent r...
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Hypertension is a major contributor to the global burden of disease. Unfortunately, hypertension is controlled in less than one-fifth of patients worldwide due to either failure to treat or lack of compliance to medication. An ideal therapy would be administered one time only and yield lifelong blood pressure control. We investigated our hypothesis...
Article
Dr Dzau was born in Shanghai. He received his Bachelor of Science in Biology and his MD degree from McGill University. He was a medical resident, Chief Resident, and the founding Chief of the Division of Vascular Medicine at the Peter Bent Brigham Hospital (now the Brigham and Women's Hospital). He moved to Stanford in 1990 as the Chief of the Divi...
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The research and development (R&D) ecosystem has evolved over the past decade to include pandemic infectious diseases, building on experience from multiple recent outbreaks. Outcomes of this evolution have been particularly evident during the COVID-19 pandemic with accelerated development of vaccines and monoclonal antibodies, as well as novel clin...
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In 2016, in anticipation of the US presidential election and forthcoming new administration, the National Academy of Medicine launched a strategic initiative to marshal expert guidance on pressing health and health care priorities. Published as Vital Directions for Health and Health Care, the products of the initiative provide trusted, nonpartisan,...
Chapter
There are currently no effective treatments to regenerate the heart after cardiac injury. Following cardiac injury, heart muscle cells, also known as cardiomyocytes, die in large numbers. The adult mammalian heart does not have the ability to replace these dead cardiomyocytes. In their place, fibroblasts invade the injury zone and generate a scar....
Article
It has been more than 2 decades since the Institute of Medicine (IOM; now the National Academy of Medicine [NAM]) published To Err Is Human in 2000,¹ which concluded that up to an estimated 98 000 deaths each year may result from preventable medical errors. In 2020, as a host of articles appeared to celebrate the anniversary of the report, the COVI...
Article
We have shown that miR combo directly reprograms fibroblasts into cardiomyocytes. However, both in vitro and in vivo, the generated cardiomyocytes are immature. Recently, we discovered that cardiomyocyte maturation is enhanced by NFkB activation. While miR combo initiates reprogramming, the effect on NFkB activity is modest. Therefore, miR combo on...
Article
Hypertension is recognized as one of the largest contributors to the global burden of disease. Unfortunately, for the majority of patients, hypertension is poorly controlled due, in part, to poor medical compliance resulting from the need to take one or more drugs, often several times daily. An ideal therapy would be administered a single time but...
Article
Induced pluripotent stem (iPS) cells provide a novel avenue to investigate how precursors differentiate into cardiomyocytes. In this study we examined our hypothesis that iPS differentiation is regulated by a balance between cardiogenic and inhibitory Wnt proteins. Recently, we have discovered that iPS cells differentiate into cardiomyocytes in res...
Article
With continued advances in science and technology, there is great potential to extend our healthspan as we age.
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Stem cell injections are an attractive therapeutic tool. It has been demonstrated that injected stem cells promote tissue repair and regeneration via paracrine mechanisms. However, the effects of injected stem cells continue for far longer than they are present. We hypothesized that the effects of injected stem cells are prolonged due a sequential...
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Full-text available
Reprogramming scar fibroblasts into new heart muscle cells has the potential to restore function to the injured heart. However, the effectiveness of reprogramming is notably low. We have recently demonstrated that the effectiveness of reprogramming fibroblasts into heart muscle cells (cardiomyocytes) is increased by the addition of RNA-sensing rece...
Article
Following heart injury, cardiomyocytes, are lost and are not regenerated. In their place, fibroblasts invade the dead tissue where they generate a scar, which reduces cardiac function. We and others have demonstrated that combinations of specific miRNAs (miR combo) or transcription factors (GMT), delivered by individual lenti-/retro-viruses in vivo...
Article
In 2019, the National Academy of Medicine (NAM) turned to the all-important state level to draw insights on the status of health and health care within the context of the NAM Vital Directions for Health and Health Care initiative. The NAM held a two-day symposium in the Research Triangle to bring together various stakeholders to better understand a...
Article
In Reply Our Viewpoint¹ was a summary of a comprehensive National Academies of Sciences, Engineering, and Medicine (NASEM) report.² Time pressure and high workload are work system factors that contribute to clinician burnout and affect patient care; however, many other work system factors can also increase clinician burnout. The review of the evide...
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A draft policy is generally supportive but should start mandating data sharing
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Policies and actions that promote clean air have been shown to provide a triple benefit - to human health, to the environment, and to the economy. Five national academies are issuing an urgent call for all stakeholders to take immediate action to combat this global threat to human health and sustainable development.
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Juxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells which give rise to JG cells or a subset of smooth muscle cells of the renal afferent arteriole. During periods of dehydration and salt deprivation renal Mesenchymal Stromal Cells (MSCs) differentiate to JG cells undergo expansion, and smooth muscle...
Article
Twenty years ago, the Institute of Medicine (now the National Academy of Medicine) published 2 important reports¹,2 in response to a crisis in patient safety that led to significant reform and improvements in quality and patient safety. It is time for another major system improvement in response to the crisis of clinician burnout. Numerous changes...
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Recognizing that aging presents a defining challenge for this century, the National Academy of Medicine is launching a Healthy Longevity Global Grand Challenge, an international effort directed at improving health, productivity, and quality of life for older people.
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The process by which fibroblasts are directly reprogrammed into cardiomyocytes involves two stages; initiation and maturation. Initiation represents the initial expression of factors that induce fibroblasts to transdifferentiate into cardiomyocytes. Following initiation, the cell undergoes a period of maturation before becoming a mature cardiomyocy...
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To the Editor: I am writing to provide additional information to clarify conflict of interest disclosures in articles I published in JAMA in 2014, 2016, and 2019.
Article
The opioid epidemic was declared a national public health emergency on October 26, 2017, and, although there have been some significant increases in federal funding and new programs to address this crisis, progress appears to be slow and the United States continues to be severely affected by substance use disorder.¹ As of 2016, approximately 2 mill...
Article
An international commission from the US National Academy of Sciences, the US National Academy of Medicine and the UK Royal Society.
Preprint
Juxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells which give rise to JG cells or a subset of smooth muscle cells of the renal afferent arteriole. During periods of dehydration and salt deprivation JG cells undergo expansion. Gene expression profiling comparing resident renal Mesenchymal Stromal Cel...
Article
The Second International Summit on Human Genome Editing, held in Hong Kong last month, was rocked by the revelation from a researcher from Shenzhen that twins were born whose healthy embryonic genomes had been edited to confer resistance to HIV. Despite widespread condemnation by the summit organizing committee, world scientific academies, and prom...
Article
Scientific and technological breakthroughs are transforming the future of medicine and health, but they inevitably carry risks and have societal implications that need to be addressed proactively.
Article
There is much interest over resident c-Kit(+) cells in tissue regeneration. Their role in cardiac regeneration has been controversial. In this study we aim to understand the in vivo behavior of cardiac c-Kit(+) cells at baseline and after myocardial infarction and in response to Sfrp2. This approach can accurately study the in vivo transcript expre...
Article
The tragic shooting at a school in Parkland, Florida, last month triggered another round of proposals from local, state, and federal policymakers about controlling firearm-related violence without violating broad interpretations of the rights to keep and bear arms provided by the U.S. Constitution. Unfortunately, there is only very sparse scientifi...
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The insulin-like growth factor 1 receptor (IGF1R) is a receptor tyrosine kinase with critical roles in various biological processes. Recent results from clinical trials targeting IGF1R indicate that IGF1R signaling pathways are more complex than previously thought. Moreover, it has become increasingly clear that the function of many proteins can be...
Article
The process by which committed precursors mature into cardiomyocytes is poorly understood. We found that TLR3 inhibition blocked cardiomyocyte maturation; precursor cells committed to the cardiomyocyte lineage failed to express maturation genes and sarcomeres did not develop. Using various approaches we found that the effects of TLR3 upon cardiomyo...
Article
Introduction: Manipulation of I nsulin-like G rowth F actor- 1 R eceptor (IGF1R) signaling has been proposed to be an important therapeutic for the treatment of heart failure and myocardial infarction. However, activation of this receptor has, under certain conditions, been shown to result in deleterious side-effects such as pathological hypertroph...
Article
Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been withdrawn from market due...
Article
Importance: Recent discussion has focused on questions related to the repeal and replacement of portions of the Affordable Care Act (ACA). However, issues central to the future of health and health care in the United States transcend the ACA provisions receiving the greatest attention. Initiatives directed to certain strategic and infrastructure p...
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This paper summarises a structured panel session regarding the cost of innovation in healthcare. The debate took place during the 2016 Simnovate Conference at McGill University. The audience, panel members and venue largely included members from academia as well as representatives from industry and organised medicine. The goal of the debate was to...
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Rationale: Direct reprogramming of cardiac fibroblasts to cardiomyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of 4 microRNAs (miR-1, miR-133, miR-208, and miR-499) that we named miR combo...
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Reports on the response to Ebola broadly agree on what needs to be done to deal with disease outbreaks. But Suerie Moon and colleagues find that the world is not yet prepared for future outbreaks In August 2014, the World Health Organization (WHO) declared the Ebola outbreak in west Africa a public health emergency of international concern, and th...
Article
We have recently shown that Hypoxia and Akt induced Stem cell Factor (HASF) protects the heart from ischemia-induced damage and promotes cardiomyocyte proliferation. While we have identified certain signaling pathways responsible for these protective effects, the receptor mediating these effects was unknown. Here, we undertook studies to identify t...
Article
We are seeing unparalleled advances in science and technology that have the potential to transform health and medicine. New technologies, data resources, research strategies, and delivery models are spurring advances in medical science and the delivery of care. However, notable challenges exist. The health system is strained by increasing demand an...
Chapter
Many studies have demonstrated that the exogenous delivery of stem cells into injured myocardium results in functional improvements. It was originally thought that the regenerative properties of these stem cells arose from engraftment into the myocardium and subsequent differentiation into cardiac cells. However, this process was found to occur ver...
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Federal health agency leaders describe plans to develop infrastructure for generating high-quality evidence to improve care. They argue that it will be necessary to embed research in clinical care, create interoperable research data networks, and apply new research methods.
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Full-text available
We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. Reprogramming of cardiac fibroblasts by miR combo in vivo is associated with improved cardiac function following myocardial infarction. However, the efficiency of direct reprogramming in...
Article
The barriers to developing precision medicines are many, starting with the translational science extending into development and the market. In development, pharmaceutical companies routinely fail to take advantage of clinical trials to explore, learn, and generate hypotheses. Too often these studies are highly focused on testing a primary hypothesi...
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Hypertension afflicts 33% of the U.S. adult population. Despite current treatments, approximately 50% of people are unresponsive to treatment. There is a critical need to develop new therapies to treat this disease and its complications. The Renin Angiotensin Aldosterone System plays a key role in regulating blood pressure in humans. Renin controls...
Article
In this Viewpoint the president of the National Academy of Medicine and colleagues describe the academy’s Vital Directions for Health and Health Care initiative to define evidence-based health policy opportunities and priorities in anticipation of a new US presidential administration. Article Information Corresponding Author Victor J. Dzau, MD, Na...
Article
Recent evidence suggests that the renin-angiotensin system (RAS) has a vital role in adipocyte biology and the pathophysiology of metabolic syndrome. Obesity is the main culprit of metabolic syndrome; and mesenchymal stem cells (MSCs) have been forwarded as a major source of adipocyte generation. Previously, we reported that MSCs have a local RAS a...
Article
The battle to contain and ultimately defeat the Ebola epidemic of 2014-2015 has been vividly described.(1)-(3) Caught off guard from the start and hindered by myriad coordination, communication, and other problems, a combination of local and international teams fought back with determination, courage, and eventually the deployment of substantial re...
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Lawrence Gostin and colleagues offer a set of priorities for global health preparedness and response for future infectious disease threats.
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In light of heavy criticism of the WHO’s handling of the Ebola outbreak, the election process for the next director general will be under intense scrutiny. Devi Sridhar and colleagues outline the key questions on epidemic preparedness for prospective candidates When the member states of the World Health Organization (WHO) elect a new director gene...
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Infectious disease crises have substantial economic impact. Yet mainstream macroeconomic forecasting rarely takes account of the risk of potential pandemics. This oversight contributes to persistent underestimation of infectious disease risk and consequent underinvestment in preparedness and response to infectious disease crises. One reason why eco...
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Full-text available
We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. However, direct reprogramming strategies are inefficient and slow. Moving towards the eventual goal of clinical application it is necessary to develop new methodologies to overcome these...
Presentation
SESSION I: Opening Remarks and Workshop Introduction

Citations

... Infectious disease outbreaks such as covid-19 present similar challenges, in that effective response and preparedness require populationlevel management in addition to direct clinical care. 2 For centuries, humanity has waged war against infections that, left untreated, would have the power to wipe out communities or even entire populations. Yet despite all our advanced scientific knowledge, only one human disease, smallpox, has been globally eradicated. ...
... 9 Where applicable, research agencies could explore including grant scoring criteria focused on the diversity of the study population and reward those applications that specifically outline plans to promote diverse enrolment. 15 Programmes like the US National Institutes of Health's Faculty Institutional Recruitment for Sustainable Transformation Initiative seek to enhance diversity among faculty and could be replicated in other settings. 16 Standardization and cost-lowering of multi-regional clinical trials designed to be agnostic to country-specific regulatory and reimbursement standards are important to generalize the progress made in HFrEF management across geographical boundaries. ...
... 10 Issues of vaccine equity and distribution became very newsworthy during the COVID-19 pandemic across a plethora of platforms including journalism (eg, commentaries and opinion pieces), [10][11][12] peer-reviewed literature, 13 global think tank reports 14 and international and governmental policy documents. 8 14 While vaccine equity is often described as a 'shared vision' (see, eg, Dzau et al, 15 ) critical scholars of political economy have exposed how the norms of neoliberal economies, along with structural racism and colonialism, have undermined the capacities of states and systems to protect health. Sparke and Williams, for example, elaborate a pathogenic metaphor ('neoliberal disease') to argue that plans, policies and practices advanced in the name of promoting wealth have been disastrous in protecting health. ...
... However, while such evaluation frameworks may serve as relevant guidelines, only recently, few of them have been extensively applied for the assessment of mature digital health tools [11][12][13][14]. Moreover, current medical device regulatory guidelines for digital health technologies [15][16][17] are, de facto, establishing their own evaluation constraints. ...
... Over the last 2 years, we have recognized that environmental health scientists, like the rest of society, are stepping up to face a "triple existential threat" to society's health, 3 namely climate change, persistent structural racism with resulting inequities, and the SARS-CoV-2 pandemic. The journal has focused on each of these as they intersect with the environmental health sciences, and continues to solicit high-impact research on these critical topics. ...