2. Program Overview
The National Heart Institute (NHI) was established in 1948 through the National Heart Act with a mission to support research and training in the prevention, diagnosis, and treatment of cardiovascular diseases (CVD). Twenty-four years later, through section 413 of the National Heart, Blood Vessel, Lung, and Blood Act (P.L. 92-423), Congress mandated the Institute to expand and coordinate its activities in an accelerated attack against heart, blood vessel, lung, and blood diseases. The renamed National Heart, Lung, and Blood Institute (NHLBI) expanded its scientific areas of interest and intensified its efforts related to research on diseases within its purview. Over the years, the Institute's areas of interest have grown to encompass genetic, genomic, and proteomic research, systems biology, sleep disorders, and the Women's Health Initiative (WHI).
The mission of the NHLBI is to provide leadership for a national program in diseases of the heart, blood vessels, lung, and blood; sleep disorders; and blood resources management. The Institute:
Each year, the NHLBI assesses progress in the scientific areas for which it is responsible and updates its goals and objectives. As new opportunities are identified, the Institute expands and revises its areas of interest. Throughout the process, the approach used by the Institute is an orderly sequence of research activities that includes:
The programs of the NHLBI, as shown in the following table, are implemented through five extramural units:
The extramural divisions use a variety of funding mechanisms, such as individual research project grants, cooperative agreements, program project grants, Small Business Innovation Research (SBIR) grants, Small Business Technology Transfer (STTR) grants, Specialized Centers of Clinically Oriented Research (SCCOR) grants, comprehensive center grants, contracts, and research training and career development programs.
Descriptions of the Divisions follow.
The DCVD supports research on the causes, diagnosis, prevention, and treatment of CVD through an integrated program of basic and clinical research, including translational research, networks, and multicenter clinical trials. Research funded by the Division is allocated among investigator- and Institute-initiated grants and contracts in disease areas such as atherothrombosis, coronary artery disease, myocardial infarction and ischemia, heart failure, arrhythmia, sudden cardiac death, adult and pediatric congenital heart disease, cardiovascular complications of diabetes and obesity, and hypertension. The DCVD fosters biotechnological research in genomics, proteomics, nanotechnology, imaging, device development, cell- and tissue-based therapeutics, gene therapy, and the development of advanced technologies, including technologies for surgery. SCCORs support clinical collaborative research in cardiac dysfunction and disease; pediatric heart development and disease; and vascular injury, repair, and remodeling.
The Division is organized into the five Branches and one Office described below.
Advanced Technologies and Surgery Branch
The Advanced Technologies and Surgery Branch supports integrated basic and clinical research to develop technologies for the diagnosis, prevention, and treatment of CVD. Research on diagnostics focuses on proteomic, genomic, and other biomarker technologies and on imaging modalities and agents. Therapeutics research focuses on tissue-, cell-, and gene-based therapies; regenerative and reparative medicine; image-guided therapies; and cardiac and circulatory support and repair devices. Research related to surgery addresses improved surgical and image-guided therapies and the translation of cardiovascular surgical advances into clinical practice. Enabling technologies research includes bioinformatics, computational and systems biology, bioengineering, nanotechnology, materials research, and personalized medicine.
Atherothrombosis and Coronary Artery Disease Branch
The Atherothrombosis and Coronary Artery Disease Branch supports integrated basic and clinical research on the etiology, pathogenesis, prevention, diagnosis, and treatment of coronary artery disease and atherothrombosis. Research on coronary artery disease focuses on acute and chronic coronary syndromes, including myocardial infarction; acute ischemia, angina, and silent ischemia; and percutaneous and surgical revascularization of stenotic and restenotic coronary lesions. Atherothrombosis research investigates atherosclerotic lesions in coronary arteries and other arterial beds; lipid fractions and interactions with the arterial wall; lesion instability, vulnerable plaques, and thrombosis; and biomarker and imaging diagnostics to quantify plaque and atherosclerosis progression. Atherothrombosis research also includes studies of diet, exercise, diabetes, obesity, and other metabolic conditions related to atherothrombosis.
Heart Development and Structural Diseases Branch
The Heart Development and Structural Diseases Branch supports integrated basic and clinical research on normal and abnormal cardiovascular development and the etiology, pathogenesis, prevention, diagnosis, and treatment of pediatric and adult structural heart disease. Research areas in heart development include normal and abnormal development, molecular and genetic etiology of cardiovascular malformations, cardiomyogenic differentiation of stem cells, and geneenvironment interactions in the development of congenital heart disease. Structural disease research includes the investigation of congenital heart disease, from embryology through adulthood, and the associated exercise physiology and neurodevelopmental outcomes; valve disease; pediatric cardiomyopathy and heart transplantation; and pediatric cardiac inflammation and infection.
Heart Failure and Arrhythmias Branch
The Heart Failure and Arrhythmias Branch supports integrated basic and clinical research on normal and abnormal cardiac function to improve diagnosis, treatment, and prevention of heart failure and arrhythmias and to protect the myocardium and manage resuscitation. Heart failure research addresses the pathogenesis and treatment of heart failure and cardiomyopathies, including the use of devices, medical treatments, and cell-based therapies. Arrhythmias research investigates the etiology of rare and common arrhythmias, sudden cardiac death, and arrhythmogenesis and explores the genetic and environmental bases of normal cardiac electrical activity. Myocardium protection research focuses on stunning and hibernation, ischemic/reperfusion injury, and preconditioning. Resuscitation research includes the study of whole-body oxygen deprivation; organ preservation; and cell, tissue, and organ protection during cardiac arrest and traumatic shock.
Vascular Biology and Hypertension Branch
The Vascular Biology and Hypertension Branch supports integrated basic and clinical research on the etiology, pathogenesis, prevention, diagnosis, and treatment of hypertension and vascular diseases. Vascular biology focuses on the biology of the vascular wall and its role in hypertension; cerebrovascular, renal, lymphatic, aneurysmal, and peripheral vascular disease; the development of arteries, veins, lymphatics, and microcirculation; and angiogenesis. Hypertension research includes the study of blood pressure regulation including central, renal, and vascular control, and cerebrovascular disease resulting from high blood pressure.
Office of Research Training and Career Development
The Office of Research Training and Career Development provides opportunities for people at a variety of educational levels, from high school students to academic faculty, to pursue and build careers in cardiovascular research. It collaborates with the scientific community and professional organizations to ensure that its programs meet the needs of young scientists from diverse backgrounds. Activities include institutional and individual research training programs and fellowships, diversity supplements to provide mentored experiences with established research scientists, the Pathway to Independence Program that allows recipients to bridge the gap between a career development award and a research award, and career development programs designed for clinical research.
The DLD supports research on the causes, diagnosis, treatment, and prevention of lung diseases and sleep disorders. Research is funded through investigator- and Institute-initiated grants and contracts in disease areas such as asthma, bronchopulmonary dysplasia, COPD, CF, sleep-disordered breathing, critical care and acute lung injury, developmental biology and pediatric pulmonary diseases, immunologic and fibrotic pulmonary disease, rare lung disorders, pulmonary vascular disease, and pulmonary complications of AIDS and tuberculosis. SCCORs support collaborative studies on COPD, pulmonary vascular disease, and host factors in chronic lung diseases.
The Division also supports demonstration and dissemination projects to transfer basic research and clinical findings to health care professionals and patients, and training and career development programs for individuals interested in furthering their professional abilities in lung diseases research. The DLD, through the National Center on Sleep Disorders Research, coordinates sleep research activities across the NIH, other Federal Agencies, and outside organizations.
The Division is organized into the three Branches described below.
Airway Biology and Disease Branch
The Airway Biology and Disease Branch supports basic and clinical research and research training in asthma, COPD, CF, and airway function in health and disease. The Branch supports innovative genetics, genomics, and biotechnology programs to advance discovery of lung disease risk factors, mechanisms, and treatment. It also funds applied studies to develop new methods of lung imaging.
Asthma research investigates the origins, pathogenesis, and management of asthma, including the role of immunologic and nonimmunologic events and inflammation in its pathogenesis; the genetics of asthma and atopy; airway remodeling and repair in asthma; the mechanisms of severe asthma; and the regulation of mucous hypersecretion and mucous cell metaplasia. A growing area of interest for the Branch is health education research and demonstration and education projects for the management of asthma.
Research on COPD and other diseases of the lung related to smoking or environmental exposures explores pathogenetic mechanisms involved in the development and progression of COPD, emphysema, and lung disease associated with alpha-1-antitrypsin deficiency; genetic determinants of lung disease; management of COPD; and properties and health effects of air pollution. The Branch is also interested in health education research and demonstration and education projects for COPD management.
Research on CF focuses on the function of the CF transmembrane conductance regulator and its role in lung disease. Areas of interest include airway epithelial ion transport, airway surface liquids, animal and cellular models for CF, signaling pathways in airway cells, regulation of mucin expression and secretion, development and clinical testing of treatments, and mechanisms underlying the infectious and inflammatory aspects of CF lung disease.
Lung Biology and Disease Branch
The Lung Biology and Disease Branch supports basic, translational, and clinical research, and research training programs in pulmonary conditions associated with human immunodeficiency virus (HIV)/AIDS, acute lung injury and critical care medicine, lung development and pediatric lung diseases, lung immunobiology and interstitial lung diseases, lymphangioleiomyomatosis, and lung cell and vascular biology.
AIDS and tuberculosis research focuses on the course and pulmonary manifestations of HIV infection and tuberculosis, including a collaborative effort to identify lung complications associated with HIV infection. The Branch supports the development of tuberculosis curricula for medical schools.
Research on acute lung injury and critical care medicine explores the pathogenesis, treatment, and prevention of acute lung injury and acute respiratory distress syndrome (ARDS). The Branch supports development of new diagnostic tools for detection of acute lung injury and development of an artificial lung and oversees clinical studies of therapies for ARDS, including the ARDS Network.
Research in developmental biology and pediatric pulmonary diseases investigates the regulation of lung development, growth, and repair and focuses on pediatric pulmonary diseases in infants and children, including bronchopulmonary dysplasia and persistent pulmonary hypertension of the newborn. Research also focuses on identification of lung progenitor stem cells and exploration of lung cell-based therapy.
Research on immunology and fibrosis includes studies of interstitial pulmonary fibrosis, sarcoidosis, occupational and environmental lung diseases, and the role of immune response and inflammation in these diseases. The Branch also supports research on lung immunobiology, lung transplantation, and pathogenesis of lymphangioleiomyomatosis.
Lung cell and vascular biology research investigates lung cell biology and function and pulmonary vascular disease, including pulmonary arterial hypertension and pulmonary embolism diagnosis. Research focuses on pulmonary alveolar epithelial cells, vascular endothelial cells, and the lung surfactant system. The Branch also includes research on the regulation of barrier function of pulmonary endothelial cells and regulation of lung permeability.
National Center on Sleep Disorders Research
The National Center on Sleep Disorders Research (NCSDR) supports research, health education, and research training related to sleep-disorder breathing and the fundamental function of sleep and circadian rhythms. Specific areas of interest include neurobiology of ventilatory control, respiratory rhythmogenesis, chemosensitivity, basic neurobiology of sleepwake regulation, circadian-coupled cellular function, and effects of sleep deprivation. The NCSDR also stewards several forums, including the Sleep Disorders Research Advisory Board and the Trans-NIH Sleep Research Coordinating Committee, that facilitate the coordination of sleep research across the NIH and with other Federal Agencies and outside organizations. The Center participates in translation of new sleep research findings for dissemination to health care professionals and the public.
The DBDR supports research on the causes, diagnosis, treatment, and prevention of nonmalignant blood diseases, including anemias, SCD, and thalassemia; premalignant processes such as myelodysplasia and myeloproliferative disorders; hemophilia and other abnormalities of hemostasis and thrombosis; and immune dysfunction. Funding encompasses a broad spectrum of research ranging from basic biology to medical management of blood diseases. SCCORs and other specialized centers support collaborative research in hemostatic and thrombotic diseases, transfusion biology and medicine, SCD, and cell-based therapy for blood diseases. The Division also has a major responsibility to improve the adequacy and safety of the Nation's blood supply. It has a leading role in applying scientific advances in transfusion medicine and stem cell biology to the development of new cell-based therapies to repair and regenerate human tissues and organs.
The Division is organized into the three Branches described below.
Blood Diseases Branch
The Blood Diseases Branch supports research and research training in blood diseases, including SCD, thalassemia, Fanconi anemia, Diamond-Blackfan anemia and other aplastic anemias and malaria. Additionally, it supports outcomes-related research. Research in SCD and thalassemia focuses on elucidating the etiology and pathophysiology of the diseases and improving disease treatment and management. Areas of emphasis include genetics, regulation of hemoglobin synthesis, iron chelation, development of drugs to increase fetal hemoglobin production, hematopoietic transplantation, and gene therapy. Basic and translational red cell research are also areas of interest.
Thrombosis and Hemostasis Branch
The Thrombosis and Hemostasis Branch supports research and research training in hemostasis, thrombosis, and endothelial cell biology, including basic research, clinical studies, and technology development. Areas of interest include hemophilia and von Willebrand disease as well as immune disorders such as idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, and systemic lupus erythematosus. Research on bleeding disorders focuses on identifying effective treatments. Emerging areas of interest are gene transfer; clinical proteomics; inflammation and thrombosis; stroke; coagulation activation; autoimmune disease; and thrombotic complications of obesity, diabetes, and cancer. The Branch also supports research on the pathogenesis of arterial and venous thrombosis to improve the diagnosis, prevention, and treatment of thrombosis in heart attack, stroke, and peripheral vascular diseases. A major goal is to find additional platelet inhibitors, anticoagulants, and fibrinolytic agents to treat thrombotic and thromboembolic disorders with better specificity and fewer side effects than those currently used for treatment.
Transfusion Medicine and Cellular Therapeutics Branch
The Transfusion Medicine and Cellular Therapeutics Branch supports research and research training in transfusion medicine, stem cell biology and disease, hematopoiesis, clinical cellular medicine, and blood supply adequacy and safety. Research focuses on the use, safety, and availability of blood and blood components for transfusion and cellular therapies. Research areas include transmission of disease, noninfectious complications of transfusions, immunobiology, cell biology and disease, novel cell-based therapies, hematopoietic stem cell transplantation, and overall product availability. The Branch develops programs for basic and clinical research related to normal and abnormal cellular biology and pathology. It also collaborates with governmental, private sector, and international organizations to improve the safety and availability of the global supply of blood and blood components.
The DPPS supports and provides leadership for population- and clinic-based research on the causes, prevention, and clinical care of cardiovascular, lung, and blood diseases and sleep disorders. Research includes a broad array of epidemiological studies to describe disease and risk factor patterns in populations and to identify risk factors for disease; clinical trials of interventions to prevent disease; studies of genetic, behavioral, sociocultural, and environmental influences on disease risk and outcomes; and studies of the application of prevention and treatment strategies to improve clinical care and public health. The Division also supports training and career development in these areas of research.
The Division is organized into the four components described below.
Clinical Applications and Prevention Branch
The Clinical Applications and Prevention Branch supports, designs, and conducts research and supports training on behavioral, environmental, clinical, and health care approaches to reduce the occurrence and consequences of CVD. Prevention research examines the effectiveness of interventions to slow or halt risk factor or disease development or progression. Interventions, many of which focus on high-risk individuals and populations, include medications, behavioral strategies, and environmental change. Studies to examine lifestyle, nutrition and exercise, psychological and sociocultural factors, and environmental and genetic influences relevant to prevention are supported. Also supported is clinical application research to examine approaches to improve health care delivery and patient outcomes. Studies include clinical and community trials and observational studies.
The Epidemiology Branch supports, designs, and conducts research and supports research training in the epidemiology of cardiovascular, lung, and blood diseases and sleep disorders. Studies are conducted to identify temporal trends and population patterns in the prevalence, incidence, morbidity, and mortality from the diseases and include single- and multicenter observational epidemiologic studies of development, progression, and treatment of cardiovascular, lung, and blood diseases and sleep disorders. Areas of emphasis include environmental, lifestyle, physiological, and genetic risk factors for disease and risk factor development including characterization of genegene and geneenvironment interactions. Large cohorts consisting of minority participants such as Hispanics and blacks have been assembled to explore health disparities in minorities. The Branch also distributes data from eligible NHLBI studies to researchers through a process that adheres to guidelines for the protection of participant privacy and confidentiality.
Women's Health Initiative Branch
The Women's Health Initiative Branch in collaboration with the National Cancer Institute (NCI), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Institute of Neurological Disorders and Stroke (NINDS), and the Office of Research on Womens Health (ORWH), supports clinical trials and observational studies to improve the understanding of the causes and prevention of major diseases affecting the health of women. Current studies focus on CVD, cancer, and fractures. Large multicenter observational studies seek to identify risk markers for disease or better quantify known markers using questionnaires, clinical examinations, and laboratory data. The large and long-term multicenter clinical trials test promising but unproven interventions such as hormone therapy, diet, and supplements, to prevent major diseases and evaluate overall effects on health. The Branch has established an infrastructure to support the use of data and blood samples from the studies by the scientific community.
The Women's Health Initiative Memory Study (WHIMS), an ancillary study to the WHI, was designed to test whether hormone therapy prevents the development and progression of dementia symptoms in postmenopausal women.
Office of Biostatistics Research
The Office of Biostatistics Research (OBR) provides statistical expertise to the Institute and performs diverse functions in planning, designing, implementing, and analyzing NHLBI-sponsored studies. Its primary responsibility is to provide objective, statistically sound, and medically relevant solutions to problems. The OBR is expected to provide a new and valid statistical solution when presented with a problem for which techniques are not yet available. Its methodological interests concern survival analysis, longitudinal data analysis, and efficient study designs, including the monitoring of ongoing clinical studies for efficacy and safety. Recently the OBR has made contributions to statistical genetics and has extended its expertise to bioinformatics.
The DIR conducts laboratory and clinical research in heart, vascular, lung, blood, and kidney diseases and develops technology related to cardiovascular and pulmonary diseases. Areas of interest include the biology of experimental and clinical arteriosclerosis and its manifestations; pathophysiology of hypertensive vascular disease; functions of the lung; clinical and experimental studies on physiologic and pharmacologic aspects of heart, lung, and blood diseases; and a broad program of other basic research and technical developments related to them.
The DIR is organized into the four Centers and three Branches described below:
Biochemistry and Biophysics Center
The Biochemistry and Biophysics Center develops a global view of the molecular basis of structure-function relationships of proteins and biologically relevant molecules. It performs state-of-the-art nuclear magnetic resonance (NMR) spectroscopy studies of protein structure and functional interactions, develops mathematical tools for generating theoretical models of protein structure-function relationships, elucidates the mechanisms of enzyme function, and investigates the relationship between protein structure-function and cell signaling pathways.
Cell Biology and Physiology Center
The Cell Biology and Physiology Center develops a global view of the mechanisms that regulate cellular function and physiology. It evaluates the mechanisms that control different molecular machines within the cytosol, including those involved in muscle contraction and cytosolic and membrane transport processes. The Center studies cellular signaling events associated with hormone action, cytosolic trafficking, and energy metabolism; investigates the role of cellular processes on function and adaptation in whole-animal model systems; and develops unique measuring devices for studying biochemical and physiological processes in intact cells, whole animals, and clinical situations.
Genetics and Development Biology Center
The Genetics and Development Biology Center develops a global view of the mechanisms that regulate cardiovascular development and the etiology of congenital heart anomalies and CVD. It evaluates the function of specific genes and transcription factors in the development of the heart and other tissues, develops techniques and approaches for gene delivery and gene therapy in model systems, and works toward a better understanding of basic processes involved in regulating and interpreting the genetic code in development and disease.
The Immunology Center develops a global view of the molecular basis of immune processes. It studies the intracellular and signaling processes involved in the activation of lymphocytes and mast cells, investigates the mechanisms by which drugs and other agents result in allergic-autoimmune reactions, and relates the results to the development of new diagnostic and therapeutic approaches in humans.
Translational Medicine Branch
The Translational Medicine Branch conducts biomedical research directed at defining at the molecular level, normal and abnormal biologic function. It develops diagnostic and therapeutic modalities for the treatment and understanding of CVD and implements mechanism-based clinical studies centered on innovative discoveries and observations from inside and outside the Branch.
The Hematology Branch conducts basic and clinical research on normal and abnormal hematopoiesis. Areas of interest include bone marrow failure, viral infections of hematopoietic cells, gene therapy of hematologic and malignant diseases, bone marrow transplantation, and mechanisms of immunologically mediated syndromes such as graft-versus-host disease and autoimmune diseases.
Pulmonary and Vascular Medicine Branch
The Pulmonary and Vascular Medicine Branch conducts research on the lung, heart, and systemic vasculature directed at definingat the molecular, biochemical, and functional levelsnormal physiological function and novel mechanisms of disease. It conducts research on emerging diseases of the lung characterized by unknown etiology and molecular pathogenesis. Areas of interest include lung diseases in blacks such as sickle cell lung disease and sarcoidosis; the role of nitric oxide, nitrite, gender, preconditioning, and mitochondrial function on the modulation of ischemia and reperfusion injury of the heart and lung; and translational study and drug development for therapeutic modulation of vascular, pulmonary, and cardiac cellular and molecular dysfunction in diseases of the lung and heart.
The DARD supports national and international research translation, dissemination, and utilization programs to speed the application of scientific advances in prevention, detection, and treatment of cardiovascular, lung, and blood diseases and to shorten the time between the discovery and delivery of research advances. Through knowledge networks, education programs, community outreach, conferences, and symposia, the Division provides opportunities for multidirectional communication and collaboration among researchers, clinical and public health practitioners, patients, and the general public. It connects research and practice by identifying knowledge gaps that should be addressed by future research; synthesizing and organizing evidence related to priority diseases and conditions; facilitating knowledge-sharing and collaboration with key stakeholders; and reaching out to people in high risk, low-income, and minority communities to eliminate health disparities.
The Division is organized into the three Branches described below.
Research Translation Branch
The Research Translation Branch synthesizes and organizes new scientific evidence related to priority diseases and conditions to facilitate rapid translation of research findings. It identifies knowledge gaps to inform future research directions and promotes the use of evidence-based reviews. The Branch develops or facilitates the development of clinical guidelines with relevant stakeholders. It also develops innovative implementation approaches for use in clinical and public health practice; maximizes opportunities for researchers and users of research to discuss research applicability, relevance, and utility; and addresses future research needs through knowledge networks and other strategies.
Enhanced Dissemination and Utilization Branch
The Enhanced Dissemination and Utilization Branch collects, synthesizes, and communicates new knowledge and recommendations for the dissemination and utilization of research-based findings to diverse target audiences, including minority and underserved groups. It provides technical assistance and information resources to NHLBI grantees to enhance their dissemination plans and practices. The Branch accelerates the introduction of evidence-based tools and education programs into community practice and establishes community-based Enhanced Dissemination and Utilization Centers to apply the latest research advances and evaluate their effects in multiple settings, achieve the U.S. Department of Health and Human Services (HHS) Healthy People 2010 goals, and eliminate health disparities.
Health Communications and Social Marketing Branch
The Health Communications and Social Marketing Branch uses the latest health and consumer communications and behavioral and social marketing research to plan health communications strategies and develops consumer messages and public education campaigns. It operates the NHLBI Health Information Center to respond to professional and public inquiries.