NIH 1998 Almanac/The Organization/NIAMS/       National Institute of Arthritis & Musculoskeletal & Skin Diseases: Research Programs The NIAMS supports a multidisciplinary program of basic and clinical investigations, epidemiologic research, research centers, and research training for scientists within its own facilities as well as supporting grantees at universities and medical schools nationwide. It also supports the dissemination of research results and information through the National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse and through the Osteoporosis and Related Bone Diseases National Resource Center. The NIAMS Intramural Research Program conducts basic research in structural biology, biology of the immune system, biology of the skin, muscle biophysics, and development of bone and cartilage. It does clinical research on lupus, rheumatoid arthritis, genetic skin diseases, and inflammatory muscle diseases. The Extramural Program supports research via grants and contracts in four branches: Arthritis; Musculoskeletal Diseases; Skin Diseases; and Muscle Biology. Support also is provided for the Epidemiology/Data Systems Program and the Centers Program. A wide array of basic and clinical research and research training in the fields of rheuma-tology, muscle biology, orthopedics, bone and mineral metabolism, and dermatology are being pursued through these programs. Arthritis Branch. This program supports basic and clinical research on the normal function and components of connective tissue and the immune system and their dysregula-tion in rheumatic, genetic, and inherited diseases of connective tissue. The goals are increased understanding of the mechanisms involved in the initiation and development of rheumatic and degenerative diseases of the joints and the translation of these basic research findings to prevention, diagnosis, and treatment of disease. The research supported by the program uses approaches emanating from immunology, pathology, physiology, behavioral medicine, and epidemiology. Some of the specific diseases being studied include rhematoid arthritis, osteoarthritis, systemic lupus erythmatosus, scleroderma, fibromyalgia, juvenile rheumatic diseases, gout, ankylosing spondylitis and other spondyloarthropathies, and many other inherited and acquired connective tissue disorders. Specific areas under investigation include: Biochemistry, physical chemistry, and metabolism of normal cartilage and extracellular matrix components. Mechanisms of dysregulation of immune function in rheumatic diseases, including development of new immunotherapies, Basic and clinical research in rheumatic diseases, including fibromyalgia, with emphasis on the development of therapies to prevent disease onset, Basic and clinical studies in osteoarthritis, Research in arthritic manifestations of chronic Lyme disease, and Inherited connective tissue disorders, including the application of gene therapy approaches. Epidemiology and Data Systems Programs. The epidemiology program provides an administrative core for efforts to encourage epidemiologic research in the fields of rheumatic, musculoskeletal and skin diseases. Epidemiologic studies of these diseases contribute knowledge related to the prevalence and economic and social burdens from these diseases, studying their natural history, identifying risk factors, and investigating disease etiologies. The data systems program fosters system-atic acquisition, storage, retrieval, and analysis of information concerning arthritis and skin diseases. Program effort is focused on assuring validity and comparability of data collected in separate institutions and integrating data resources with data needs. Musculoskeletal Diseases Branch. This program supports studies of the skeleton and associated connective tissues. Broad areas of interest include skeletal development, metabolism, mechanical properties, and responses to injury. Research on osteopor-osis, a disease afflicting many of the Nation's growing population of older people, is a major area of emphasis. Some other diseases and skeletal disorders under investigation are osteogenesis imperfecta, a genetic disorder that leads to fragile, easily fractured bones; Paget's disease of bone, which results in irregular bone formation and subsequent deformity; genetic disorders of bone growth and development, such as osteomalacia. Other studies focus on the causes and treatment of acute and chronic injuries, including carpal tunnel syndrome, repetitive stress injury, and low back pain. The program supports development of technologies with the potential to improve treatment of skeletal disorders and facilitate the repair of trauma in the normal skeleton. These include drugs and nutritional interventions, joint replacement, bone and cartilage trans-plantation, and gene therapy. Sports medicine and musculoskeletal fitness are also areas of special research emphasis. Research areas support through this branch include: Bone diseases   Epidemiology and development of disease   Environmental and genetic risk factors   Treatment, prevention, and diagnosis. Bone biology   Mechanisms of bone resorption   Hormone, growth factor, and cytokine effects on bone-resorbing and bone-forming cells   Regulation of bone growth and development   Interactions among proteins, minerals, and cells in bone   Mechanisms of mineralization. Orthopedic research   Skeletal architecture and mechanical properties   Mechanisms of fracture repair   Biomaterials, orthopedic devices, joint replacement and repair   Rehabilitation Muscle Biology Branch. This program supports researchs on skeletal muscle, its diseases and disorders, and its central role in human physiology and exercise. Topics include the molecular structure of muscle and the molecular mechanisms that produce force and motion. An aim is understanding the alterations in muscle resulting from increased exercise and, conversely, the atrophy that follows immobilization during injury or illness. Specific aims include understanding the molecular structure and assembly of muscle components, including those respons-ible for contraction and regulation of muscle action; the molecular basis of genetic muscle diseases, such as Duchenne/Becker muscular dystrophy, myotonic dystrophy, myotonias, and malignant hyperthermia; genetic pro-cesses of muscle development and assembly; musculoskeletal fitness, metabolism, and adaptive mechanisms; the role of growth factors and hormones; altered metabolism during aging; the effects of therapeutic drugs and abused substances on basic muscle processes; the cellular basis for impaired muscle function in disease; inflammatory muscle diseases and inflammation resulting from exercise or injury; molecular mechanisms of muscle repair and regeneration; and development of more satisfactory methods of treatment and recovery. Specific research covered by the branch include: Muscle physiology Structure and function of muscle and of individual muscle proteins Mechanisms of muscle contraction and force generation Muscle development and specialization Musculoskeletal fitness and adaptive biology, including exercise physiology Muscle diseases and disorders Sports medicine, muscle injury and repair. Skin Diseases Branch. Research studies supported by this program are increasing understanding of the mechanisms underlying normal and abnormal skin function and development. Research investigations are conducted on the molecular structures of various skin cells, the immunologic functions of the skin in normal and disease conditions, and the development of diagnostic tests and effective therapies for an array of skin diseases that can cause discomfort, disfigurement, and/or chronic disability. The range of skin diseases include keratinizing disorders such as psoriasis and ichthyosis atopic dermatitis and other chronic inflammatory skin disorders blistering diseases such as epidermolysis bullosa and pemphigus and disorders of pigmentation such as vitiligo and disorders of the hair and nails. Basic science and disease areas in skin research include: Metabolic studies of skin Immunologically mediated skin disorders Disorders or keratinization, pigmentation, and hair growth Photobiology, photoallery, and phototoxic reactions Bullous diseases and the basement membrane of skin Acne and physiologic activity of sebaceous glands Skin manifestations of diffuse connective tissue disorders Heritable connective tissue diseases Skin manifestations of HIV infection and AIDS. Centers Program. The NIAMS currently supports three types of research centers programs: Multipurpose Arthritis and Musculoskeletal Diseases Centers, Specialized Centers of Research, and Skin Diseases Research Centers. The Multipurpose Arthritis and Musculoskeletal Diseases Centers were established in the National Arthritis Act of 1974. The purpose of these centers, located at 14 medical institutions and hospitals around the country, is to foster a multidisciplinary approach to the many problems or arthritis and musculoskeletal diseases and to develop capabilities for research in these areas. To this end, centers develop and carry out basic and/or clinical research studies, research in professional and patient education, and epidemiology and health services research. Existing Specialized Centers of Research (SCORs) are targeted for rheumatoid arth-ritis, systemic lupus erythematosus, osteo-arthritis, and osteoporosis. These centers aim to accelerate the pace of basic research on the causes of disease and to expedite transfer of advances in basic science into clinical applications and improved patient care. NIAMS has six Skin Diseases Research Centers (SDRC), which promote collaborative efforts among scientists engaged in high-quality research related to a common theme. By providing funding for core facilities, pilot and feasibilty studies, and program enrichment activities at the SDRC, the institute reinforces and amplifies investigations already ongoing. Information and Education Efforts. The focus of most NIAMS information and education efforts is in the Office of Scientific and Health Communications. The efforts include the National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse, which helps lay and professional audiences locate materials and information, and a campaign entitled "What Black Women Should Know About Lupus." A National Resource Center on Osteoporosis and Related Bone Diseases provides public information and develops educational efforts on prevention, diagnosis, and treatment. Intramural Research Program The NIAMS intramural program has six main components--the Arthritis and Rheumatism Branch, Laboratory of Physical Biology, Laboratory of Skin Biology, Laboratory of Structural Biology, Protein Expression Laboratory, and craniofacial development section--the first section within a planned Bone and Connective Tissue Biology Branch. The Arthritis and Rheumatism Branch (ARB) conducts a variety of investigations--basic and clinical. The historical focus of the ARB has been the study of the autoimmune rheumatic diseases--particularly rheumatoid arthritis, systemic lupus erythematosus, and myositis. At present, studies in the laboratories and clinics also focus on genetic diseases affecting inflammation and the musculoskeletal system, the basic mechanisms of signal-ing in the cells of inflammation, animal models of disease, genetic-epidemiologic studies, the role of neuroendocrine-immune system interactions in disease, and a variety of novel approaches to the interruption of inflammation. In the Laboratory of Physical Biology leading-edge physical and biological techniques are used to study biological systems. Efforts are devoted to studying the structure of muscle cells, the molecular structure and function of various muscle components, and the mechanism of muscle contraction. Significant effort also is directed at the study of target sizes of macromolecules by radiation inactivation. The mechanism of cell membrane assembly is being investigated by means of calorimetry. The Laboratory of Skin Biology conducts basic and clinical research on the skin and skin diseases, with particular emphasis on the epidermis--the outermost layer of skin. Basic research includes study of the various structural proteins and enzymes, and their genes, that are specifically expressed in the epidermis; the processes by which these molecules are assembled to form a normal epidermis; and the processes of abnormal cornification (keratinization) that occur in a variety of genetic skin diseases. One section within the lab uses direct and indirect genetic approaches to identify the molecular bases of disorders of cornification and malignant skin diseases. This section also assists in genetic analysis of a variety of hereditary diseases under study by other NIH investigators, including complex hereditary disorders such as arthritis. The Laboratory of Structural Biology conducts research into the structural basis of the assembly and functioning of macromolecules (large biological molecules) and their complexes such as viruses, cell membrane and cytoskeletal proteins, and proteins in the skin. There is particular interest in the mechanisms that control these processes. These investigations make extensive use of cryoelectron microscopy and three-dimensional image processing. The newest group in this laboratory, established in 1991, is devoted to x-ray crystallographic study of the high-resolution structure and function of biolgical macromolecules and multienzyme complexes, including the replication complex of bacteriophage T4, retroviral proteins, and host factors involved in HIV expression. The Protein Expression Laboratory, form-erly under the NIH Office of the Director, joined the NIAMS in 1996. This lab plans and conducts research on the expression, purification, and structural characterization of HIV and HIV-related proteins. Laboratory scientists also collaborate with NIH intramural researchers studying the structure and function of HIV and HIV-related proteins. The lab serves as a support and resource group for the expression and purification of these proteins. The craniofacial development section, established in 1996, conducts basic investigations at the molecular and cellular levels on the mechanisms of bone and cartilage formation as they relate to human genetic diseases such as achondroplasia, craniosyno-stosis, craniofacial dysostosis, and various other forms of skeletal dysplasias. Signal transduction pathways that determine and maintain cartilage and bone formation are of particular interest. Members of the lab will use relevant animal models combined with the power of molecular genetics to address fundamental questions in bone and cartilage development and extrapolate their findings to shed light on the cause and development of human skeletal diseases.

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