The mission of the NHLBI Division of Intramural Research (DIR), otherwise known as the Bethesda Labs, is to perform robust scientific and clinical research that leads to a better understanding of biology and clinical pathology. To attain this goal, we have built a strong basic science foundation and coupled it closely with innovative technology development and outstanding clinical research, both at the NIH Clinical Center and in partnership with local hospitals. The purview of our research is broad, encompassing investigations into the basic principles of molecular, cellular, and organ-level biology and their relationship to disease.
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Some current areas of fundamental interest include single molecule structure, protein assembly, molecular and cell biology, cell signaling and motility, membrane trafficking, physiology, systems biology, and engineering and technology development. Insights into disease mechanisms derived from basic studies form the basis for translational research into new diagnostic and therapeutic approaches.
DIR investigators also conduct concept-based clinical studies in the areas of interventional and surgical cardiology, pulmonary medicine, sickle cell anemia, bone marrow transplant, and hematologic disorders. The Center for Population Studies, located in Framingham, Massachusetts, is associated with the Framingham Heart Study and focuses on the epidemiology of cardiovascular disease.
Providing state-of-the-art training in basic, translational, and clinical research for the next generation of scientific and clinical leaders is a high priority. The DIR provides opportunities for scientists and trainees to work together towards a better understanding of molecular machines, the cell, the body, and ultimately the treatment of human diseases.
Each year DIR presents the NHLBI DIR Orloff Science Awards, which recognize achievements in science or scientific groundwork that produced clear results during the previous calendar year. The Orloff winners are scientists, clinicians, and other individuals within the DIR who contributed substantively to work in their respective fields, helping to make advances toward healing various diseases.
The Biochemistry and Biophysics Center carries out research that brings chemical and physical approaches to the study of biological problems. The principal investigators of the Center focus on topics that range from DNA transcription to cellular degeneration. To understand the mechanisms involved in these diverse processes, the investigators develop instruments and techniques to resolve, quantify, model, manipulate, and simulate biological mechanisms at molecular and cellular levels. The focus of Center research is to develop both experimental and theoretical models of biomolecular structure, and use these models to discover the link between the structure, function, and regulation of biologically active molecules and processes.
The Cardiovascular Branch conducts research on diseases that affect the heart and blood vessels. Specific projects aim to answer clinically relevant questions using methods ranging from molecular level studies to clinical projects in diagnostics, therapeutics, and interventions. The Branch places a strong emphasis on creating an environment where scientists and physician scientists can work together on disease-specific issues using the most appropriate approaches available in the spectrum between the bench and the bedside.
The Cell and Developmental Biology Center aims to understand the molecules and the molecular interactions inside cells that build the organelle systems that support basic and specialized functions to control cell fate and behavior. This Center studies how cell behavior guides normal development, including the creation and maintenance of tissues and organs. Researchers combine biochemical, molecular, cellular, genetic, and quantitative approaches to investigate fundamental biological processes across a range of organisms, including fish, flies, mammals, microbes, and viruses. This Center also seeks to apply its basic cell and developmental biological research to the understanding and treatment of human diseases.
The Cellular and Molecular Therapeutics Branch, one of the newest branches of the NHLBI, helps to accelerate the translation of basic discovery to therapeutic application. Branch investigators are leading experts on transplantation immunology, regenerative therapies for inherited blood disorders, and early sickle mortality prevention, all of which claim international stature and recognition for advancing the field of hematology.
The mission of the Epidemiology and Community Health Branch (ECHB) is to deploy innovative multimodality ascertainment and analytical approaches with a unifying focus on the phenotypic expressions of heart, lung, blood and sleep (HLBS) diseases, their occurrence and outcomes in populations.
Investigators in the Hematology Branch (HB) study normal and abnormal hematopoiesis—the development and differentiation of stem cells into multiple types of blood cells—in the clinic and in the research laboratory. Patients who have a variety of bone marrow failure syndromes and acute and chronic leukemias attend the HB’s clinic and may be enrolled in clinical research protocols at the NIH Clinical Center. Interventions are intended to reverse marrow failure, cure or ameliorate leukemias by stem cell transplant, and control lymphoproliferative diseases like chronic lymphocytic leukemia by drug therapy. In the laboratory, basic cellular and molecular biology, immunologic, and genomic techniques and approaches are used to study patient samples, cells, cell lines, and in animal models. The Branch has been an international leader in developing understanding of the pathophysiology of hematologic diseases and improving their outcomes.
The Immunology Center conducts research into the molecular basis of immune processes that are applicable to a broad range of diseases, including a number of inherited immunodeficiencies, cancers, autoimmune diseases, and allergic diseases. Center investigators explore research areas, including the normal function, signaling processes, gene regulation, and epigenetics related to the activation and function of immune cells. The goal of the Center is to understand fundamental mechanisms of biology and to promote the translation of these findings into the development of new diagnostic and therapeutic approaches in humans.
The Population Sciences Branch formulates a global view of both the natural history and future trends related to heart, lung, blood, and sleep disorders, taking advantage of the thousands of participants in the Framingham Heart Study, as well as other population cohorts. The Branch takes a comprehensive approach towards an understanding of these disorders, combining classical epidemiology and longitudinal studies with state-of-the-art genetic and -omics technologies. (-Omics refers to the measurable differences or changes in biological molecules, such as genes, metabolites, and proteins.) Through this combined approach, the Branch seeks to identify molecular signatures of disease phenotypes in the population setting.
The Pulmonary Branch conducts clinically oriented research into diseases and disorders affecting the lungs and respiratory tract. The spectrum of research spans from molecular and cell based investigation to bedside and population based studies. The Branch also provides clinical pulmonary physiologic testing, consultative and advanced bronchoscopic services and offers specialty research training of pulmonary and critical care clinical fellows.
The Sickle Cell Branch conducts research to understand sickle cell disease and identify markers of disease severity. Specific projects aim to better predict long-term outcomes and to develop therapies through genetics and genomics. Researchers in this Branch also study how genes influence disease symptoms such as pain and vascular complications, as well as new approaches for better outcome in bone marrow transplant and gene therapy. The Branch is a leader in the Department of Health and Human Services (HHS) sickle cell program, which fosters government-wide collaboration to rapidly move basic discoveries to treatments for patients.
The aim of the Systems Biology Center is to create integrated models of complex biological processes and test them across the entire cellular and physiological network of interactions. Using high-throughput screening tools from the genomic, proteomic, and imaging arenas, coupled with powerful computing and modeling tools to integrate acquired data, Center investigators can examine gene and protein expression, enzyme activity, or other biological processes in a spatial and temporal context. Researchers in the Systems Biology Center are interested in diverse systems, such as cardiac disease, oxidative stress, cellular differentiation and memory, cell energetics and metabolism, and kidney function.
The Translational Stem Cell Biology Branch focuses on understanding the basic biology and the clinical applications of stem cells, focusing on hematopoietic stem cells responsible for producing all blood cells and on induced pluripotent stem cells able to form a wide variety of tissues and organs. Our mission is to gain a better understanding of the processes that control self-renewal, differentiation and normal and abnormal functioning of hematopoietic and pluripotent stem cells in vivo, focusing on models with direct relevance to human biology and disease. We develop safe and effective gene, cell and small molecule therapies for a wide variety of serious human diseases, focusing on disorders of hematopoiesis and the cardiovascular system.
The Translational Vascular Medicine Branch (TVMB) engages in research focused on the understanding of vascular diseases in human and model organism. The core principle of the TVMB is to study vascular disease mechanisms to develop novel treatment strategies to better serve our patients with vascular diseases. TVMB investigators employ genomic and molecular high throughput approaches to help understand diseases processes, particularly in atherosclerosis, inflammation, vascular calcification/occlusion and connective tissue changes in common and rare inherited disease populations. TVMB is a leader in vascular precision medicine translating discovery into treatment for patients with vascular diseases.
Core Facilities provide scientific resources, cutting-edge technologies and novel approaches to support DIR scientists. Availability of specialized expertise creates a robust environment for conducting a wide range of studies and accelerates the pace at which scientific discovery can take place.
The Office of the Scientific Director has established several programs and initiatives centered around a particular modality or disease, with the goal of speeding research discoveries towards clinical application. Current DIR programs focus on medical imaging and sickle cell disease.
The Office of the Clinical Director (OCD) serves to support the mission of the NHLBI Intramural clinical program by conducting outstanding investigator-initiated research, discovering mechanisms of disease, and developing novel devices, diagnostics, and therapies to benefit patients. The OCD is responsible for the oversight of the clinical research portfolio of the NHLBI’s DIR. As part of this oversight, the OCD develops and implements policies related to the conduct of human subjects research, ensuring that the clinical research programs of the Division are consistent with the overall mission of NHLBI and NIH and that they are in compliance with NIH and HHS policies guiding the conduct of clinical research. The OCD also oversees in-patient and out-patient clinical programs, and ensures the scientific integrity and quality of the clinical research and clinical care conducted by NHLBI staff. The OCD works directly with and supports the Scientific Review Board, the Institutional Review Board, and the Data Safety and Monitoring Board to ensure that the highest standards of clinical research are met.
The OCD is the interface between the NHLBI and the NIH Clinical Center, which houses the inpatient units and clinics, where patients enrolled in intramural NHLBI clinical trials are treated. The Clinical Director exercises medical direction and supervision of all clinical services and assures the quality of medical care delivered to these patients.
One of the most important activities of the OCD is to manage a comprehensive infrastructure supporting and facilitating the intramural clinical research program, which includes an Office of Clinical Affairs (OCA), clinical research nurse support, patient care coordinators, an office of research education, training and safety, protocol navigators, oversight of all investigator initiated IND/IDEs, a comprehensive data management program, which includes data managers, trial monitors and an FDA-compliant DIR clinical research database, an office of protocol recruitment, and bio-statistical support for trial design and analysis. These efforts are intended to ensure that all investigators within the DIR conducting clinical research are compliant with regulations guiding good clinical practice and are supported in their endeavors with an outstanding research support system. They also promote the recruitment and retention of talented young investigators wishing to conduct investigator-initiated clinical research at the NHLBI.
The NHLBI DIR’s clinical research program is one of the largest within the NIH supporting more than 180 active clinical research protocols, 650 inpatient admissions resulting in 5,700 patient/days in the Clinical Center and 14,000 outpatient visits.
The Office of the Scientific Director (OSD) is responsible for programmatic oversight, review, and administration of the intramural research program at NHLBI. The Office has several key functions, including planning, coordinating, and directing the basic and clinical scientific research programs conducted within DIR; encouraging implementation of new technologies, application of new techniques and treatments through clinical trials, and promoting research collaboration; serving in an advisory role to the Center and Branch Chiefs and Institute Director; developing and maintaining the necessary scientific capability in the Division to foster and guide an effective research and clinical program; and participating in the planning and directing of Institute resource allocation and providing senior level administrative support to the DIR programs.
The Division of Intramural Research (DIR) is the basic and clinical intramural research program (IRP) of the National Heart, Lung, and Blood Institute. The purview of our research is broad, encompassing investigations into the basic principles of molecular, cellular, and organ-level biology and their relationship to disease. DIR investigators also conduct concept-based clinical studies in the areas of interventional and surgical cardiology, pulmonary medicine, sickle cell anemia, bone marrow transplant, and hematologic disorders.
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