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,
- 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
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 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
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
- Mechanisms of muscle contraction and force generation
- Muscle development and specialization
- Musculoskeletal fitness and adaptive biology, including
- 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
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
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.