Cardiovascular Branch

In the heart, interruption of the blood supply can result in cardiac cell death and irreversible muscle damage. The Laboratory of Cardiac Physiology, led by Dr. Elizabeth Murphy, studies the molecular mechanisms involved in cardiac cell death, as well as the mechanisms that protect the heart against damage. The knowledge gained from these studies may help identify novel therapies to reduce cardiac injury during ischemia and reperfusion. Dr. Murphy’s laboratory is currently examining whether selective estrogen receptor modulators (SERMs), can mediate cardioprotection in a similar fashion to endogenous estrogen, opening up a possible therapeutic avenue to reduce heart attack damage in women.

Ischemic heart disease is a leading cause of death in the U.S.  Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) have been studied as a therapy to improve cardiac function following acute or chronic ischemia. The Laboratory of Cardiovascular Biology, led by Dr. Leslie Kennedy, investigates pathways and mechanisms that can be exploited to ultimately benefit patients prone to cardiovascular pathologies. More specifically, the lab focuses on identifying novel regulators of CM maturation, establishing mechanisms by which these proteins function in Cardiomyocytes (CMs) maturation, and assessing improvements in maturation that result from perturbing expression or function of these proteins.

Earlier work in Dr. Hwang’s lab revealed that p53, one of the most commonly mutated tumor suppressor genes that controls multiple pathways involved in cell growth, also regulates the mitochondria as part of its adaptive activities against oxidative and other cellular stresses. The research group has performed basic and translational studies focusing on this link between cancer and mitochondrial metabolism and provided mechanistic insights for developing new cancer prevention strategies. Their work has also shown that p53 can protect the mitochondrial genome and prevent chemotherapy-induced heart failure, an observation that they are further dissecting molecularly and translating to the clinics. While continuing to examine the role of p53 in cardiac muscle homeostasis, they have recently identified specific mitochondrial genes that regulate the skeletal muscle for exercise adaptation and in chronic fatigue syndrome. The goal of these studies is to translate them for developing new strategies for improving and maintaining cardiovascular health.

Computed tomography (CT) is a non-invasive advanced imaging test that uses x-rays to make three-dimensional pictures of the body. The Cardiovascular CT Program is focused on the development of and implementation of new imaging techniques to better diagnose heart disease and plan treatment options. This program, led by Dr. Marcus Chen, utilizes state-of-the art scanner hardware, advanced image reconstruction methods, and computational resources with a goal to reduce the overall radiation exposure needed to image a patient and detect cardiovascular disease. These new imaging techniques are not confined to the heart and vascular system, but also are being applied to other parts of the body such as the lung.

The Cardiovascular Intervention program creates new catheter based treatments and devices for structural heart disease and introduces them into medical practice, under both X-ray and real-time MRI guidance. His multidisciplinary team includes cardiologists, imaging physicists, biomedical engineers, and other researchers. The program has invented procedures and devices since used on thousands of patients, including transcaval access to the aorta, BASILICA aortic leaflet modification to prevent coronary obstruction from transcatheter aortic valve replacement (TAVR), LAMPOON and ELASTIC mitral leaflet modification to enable transcatheter mitral valve implantation, mitral cerclage ventriculoplasty, MRI heart catheterization, and many others. These procedures and protocols are possible through a network of collaborating structural heart interventional cardiologists across the United States.

The Clinical Physiology Laboratory, led by Dr. Marcus Carlsson, focuses on developing new understanding of the mechanisms of heart failure, by means of linking technical developments of new Magnetic Resonance Imaging techniques to pre-clinical and clinical models of heart failure. Dr. Carlsson has worked with both experimental and clinical research with the aim to quantify pumping physiology, myocardial perfusion, intraventricular blood flow, tissue viability, and valvular function. Of particular importance to him is developing and validating new methodologies in multi-disciplinary collaboration with engineers.

The Echocardiography Laboratory, led by Dr. Vandana Sachdev, performs comprehensive cardiac imaging for NHLBI and all institutes at the NIH Clinical Center. Researchers collaborate in prospective and retrospective cardiovascular phenotyping studies and implement new technologies for detailed assessment of ventricular systolic and diastolic function, valvular abnormalities, and structural heart disease.

The Laboratory of Inflammation and Cardiometabolic Diseases, led by Dr. Nehal Mehta, focuses on the role of innate immunity and inflammation in the development of cardiovascular and metabolic diseases. Using a trans-disciplinary approach that involves genetic epidemiology, translational medicine, and novel cardiovascular imaging approaches, Dr. Mehta and his team study how inflammation affects insulin resistance, the development of metabolic syndrome, and lipoprotein dysfunction, all of which are risk factors for atherosclerosis and cardiovascular disease.

The Minority Health and Health Disparities Laboratory focuses on health and health care disparities among racial and ethnic minority populations. The three main areas of lab research are: (1) Tobacco use behavior and its relation to other substance use, unhealthy behaviors, migration-related social determinants, chronic stress, and mental health among Latinos of different national heritages; (2) Differential risk of lung cancer in racial and ethnic minority populations, as shown by metabolic biomarkers of nicotine and tobacco-specific carcinogens; and (3) Relationships of migration- and environment-related social determinants of health with chronic diseases, such as diabetes. The Minority Health and Health Disparities Laboratory is led by Dr. Eliseo Pérez-Stable, who is also the director of the National Institute on Minority Health and Health Disparities.

The Laboratory of Mitochondrial Biology and Metabolism, led by Dr. Michael N. Sack, focuses on modifications of proteins that play pivotal roles in metabolism and mitochondrial function to understand how these modifications affect disease risk. The major regulatory proteins being explored in the Sack laboratory include SIRT3 and GCN5L1. The effects of these nutrient- and stress-regulatory proteins on mitochondrial biology and metabolism are explored in the context of disease pathophysiology with studies in both experimental systems with translation to the human subjects. The objective of these studies is to understand how nutrient- and other stress- signaling events cause or exacerbate disease and whether therapeutic interventions can be tested that reverse these pathologies. Current diseases being explored include cardiovascular disease, insulin resistance and immune activation.

Magnetic resonance imaging (MRI) is an established medical imaging modality, providing unparalleled soft tissue contrast combined with good spatial resolution. MRI also has the potential to provide more than just anatomical imaging, e.g. image guidance for interventional procedures, multidimensional information and tissue characterization. The MRI Technology program, led by Adrienne Campbell-Washburn, is focused on the development of advanced cardiovascular MRI techniques, leveraging modern acquisition and reconstruction techniques, as well as state-of-the-art computational resources (GPUs and cloud computing) in the clinical environment. Specifically, the aim is to improve imaging speed, imaging for MRI-guided interventions, motion robustness, quantification, and clinical workflow.

The primary research interest of the Laboratory of Obesity and Aging Research, led by Dr. Jay H. Chung, is understanding how aging and obesity affect energy metabolism and mitochondrial function and vice versa. The laboratory is elucidating the mechanisms by which aging and obesity causes mitochondrial loss and how mitochondrial dysfunction contributes to aging phenotype, including inflammation. Dr. Chung leads a translational research team seeking to discover novel therapies for diseases such as type 2 diabetes, cardiovascular diseases, neurodegeneration and autoimmune diseases by studying how mitochondrial stress affects cellular function.

The broad interest of the Laboratory of Obesity and Metabolic Diseases, led by Dr. Haiming Cao, is to understand the complex regulation of energy metabolism and uncover its significance in the pathogenesis of metabolic disease. The worldwide obesity epidemic—along with an array of obesity-related disorders, particularly diabetes, fatty liver and cardiovascular diseases—has become a major public health concern for the 21st century. The molecular and pathological basis by which obesity induces metabolic disorders, however, remains only partly understood, hampering the development of effective therapies against these debilitating diseases. To address these challenging questions, the lab has recently uncovered that hundreds of long noncoding RNAs (lncRNAs), a novel class of RNAs that are produced by 90 percent of the human genome, function as vital regulators of energy metabolism. The lab has also established a humanized mouse model in which over 90 percent of the mouse liver cells are replaced by human hepatocytes, or essentially mice carrying a human liver, and is currently using this powerful model to directly study the pathophysiological significance of lncRNAs in human diseases.

It is safe to say that during the decades in which obesity has become an epidemic in the United States, the human gene pool has not been concomitantly altered. Thus, although biology and heredity do play a role in susceptibility to obesity and obesity-related disorders, the social, behavioral, and environmental contributions cannot be overlooked if effective prevention and treatment strategies are to be designed. The Social Determinants of Obesity and Cardiovascular Risk Laboratory, led by Dr. Tiffany Powell-Wiley, focuses on the social determinants of obesity and obesity-related cardiovascular risk factors that contribute to racial and ethnic disparities in cardiovascular disease. Dr. Powell-Wiley’s hope is that through a better understanding of how socioeconomic, psychosocial, and environmental factors impact obesity as a cardiovascular risk factor, she can develop interventions to reduce obesity and improve cardiovascular health tailored to community-based environments.