- Director's Overview
- IC Fact Sheet
- Major Changes in Budget Request
- Justification of Budget Request
- Program Descriptions
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is the primary Federal agency supporting biomedical research on diseases of the bones, joints, muscles, and skin. The NIAMS mission is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases.
Arthritis and musculoskeletal and skin conditions affect people of all ages and racial and ethnic backgrounds. Combined, they afflict tens of millions of Americans, cause tremendous human suffering, and cost the U.S. economy billions of dollars in health care costs and lost productivity. For instance, a 2019 study on the prevalence and impact of musculoskeletal diseases found these conditions to be the second leading cause of years lived with disability (YLDs) worldwide. Other research suggests that the true prevalence and burden of musculoskeletal conditions may be underestimated. In a survey examining the impact and prevalence of one common musculoskeletal condition, nearly 40 million U.S. workers reported experiencing low back pain over a 3-month period. If the prevalence rates of musculoskeletal diseases continue their current trend, their associated negative impacts are likely to become even more pronounced.
NIAMS conducts and supports a broad portfolio of biomedical and behavioral research activities. The NIAMS Strategic Plan for FY 2020-2024 communicates the Institute’s perspective and vision for how supported research may lead to meaningful improvements in human health. Importantly, NIAMS continues to value and support meritorious investigator-initiated research ideas while embracing opportunities for collaborations with other NIH components, advocacy organizations, and industry to fund larger scale, team science approaches. In addition, NIAMS is committed to keeping the research talent pipeline robust and diverse. Fostering early-stage investigators and supporting a range of research training and career development programs for mid-career clinicians and scientists are key program goals of the Institute.
NIAMS also stimulates innovative research concepts that may lead research into entirely new and unexpected pathways. For example, NIAMS’ Research Innovations for Scientific Knowledge (RISK) program is designed to promote scientific innovation by encouraging the submission of projects that are considered too risky, controversial, or unconventional for other programs. In keeping with the Institute’s long-term commitment to early-stage investigators, NIH recently created the Stephen Ira Katz Award in memory of the late longtime director of NIAMS. The award is designed to support early-stage investigators who propose innovative and unique ideas that represent a significant change in research direction from their past research or training experience. A distinct feature of this program is that applications must not include preliminary data, thereby filling a gap in the NIH portfolio of funding opportunities long identified by Dr. Katz.
Overall, NIAMS will foster a rich and adaptable research environment that enables scientists at all levels to capitalize on opportunities as they arise and stimulate new areas that are unexpected and transformative.
Basic research investments leading to today’s treatments
Over the past six years, the NIH, in collaboration with public and private organizations, has supported the Accelerating Medicines Partnership (AMP) in rheumatoid arthritis (RA) and lupus to spur research on the molecular and cellular causes of those diseases. The effort uses high-dimensional, single-cell analytics on tissue biopsies from RA and lupus patients to discover cells and pathways active in disease tissues and identify promising targets for future drug development. One of the most important legacies of the AMP RA/lupus program is the rich dataset it has generated and made available to the research community. Investigators are now using the data to facilitate RA and lupus research. For example, NIAMS-funded researchers studying periodic worsening of RA, known as flares, compared changes in blood samples collected over time from a cohort of RA patients with joint–specific gene signatures derived from the AMP RA data. The comparison aided the researchers in identifying potential molecular markers that could predict an imminent RA flare. Another NIAMS-supported group studying lupus nephritis (LN), a common severe manifestation of lupus, demonstrated in a LN mouse model that hypoxia (oxygen deficiency) causes T cells infiltrating the kidneys to overexpress the regulatory transcription factor HIF-1, which drives inflammation and tissue damage. Analysis of the AMP data helped the scientists to show that the HIF-1 signaling pathway is also enhanced in kidney biopsy samples from people with LN.
The NIH is planning for a new phase of the program called AMP Autoimmune and Immune-mediated Diseases (AMP AIM). AMP AIM would extend the methods used to investigate RA and lupus to the study of other conditions such as Sjogren’s syndrome, psoriasis, and psoriatic arthritis. As envisioned, AMP AIM would refine and extend the single-cell analysis of tissues to additional diseases and employ high-dimensional novel analytics to discover how innate and adaptive cells of the immune system and tissue resident cells work together to drive inflammation, injury, abnormal function, and clinical disease.
In the early 1990s, NIAMS intramural investigators and colleagues identified and characterized the JAK-STAT pathway, a key component that controls immune cells’ activity. It was one of the earliest demonstrations of how molecules outside a cell control gene expression inside a cell. This landmark discovery, in combination with the identification of defects in the same pathway as the underlying cause of an immune-deficiency syndrome in children, led researchers to hypothesize that targeting the JAK-STAT pathway could treat a wide range of diseases affecting the immune system. NIAMS intramural researchers partnered with industry in the development of such therapeutics, leading to a new class of JAK pathway inhibitory drugs, called Jakinibs. This class of drugs continues to be pursued for a variety of diseases ranging from certain cancers, to autoimmune diseases such as ulcerative colitis and psoriatic arthritis, to dermatologic diseases like alopecia and eczema. Interestingly, one of the Jakinibs, baricitinib, was evaluated through the National Institute of Allergy and Infectious Diseases’ (NIAID) Adaptive COVID-19 Treatment Trial (ACTT) as a supplemental treatment with remdesivir for hospitalized patients with COVID-19. The clinical trial (ACTT-2) met the primary endpoint in reducing recovery time for patients receiving both drugs versus remdesivir alone. Follow-up studies are continuing. NIAMS scientists with expertise on the basic mechanisms of these drugs continue to consult and advise research partners as they develop and evaluate new or repurposed Jakinibs as novel treatments.
Responding to public health needs
Through the Helping to End Addiction Long-termSM (HEAL) Initiative, NIH is addressing the urgent public health need to combat the opioid crisis, including research to improve understanding of chronic pain and the development of new non-addictive pain treatments. NIAMS is contributing to HEAL by leading a multi-Institute and Centers effort called the Back Pain Consortium (BACPAC) Research Program. BACPAC seeks to spur new treatments for chronic low back pain (cLBP)—one of the most common forms of pain among adults worldwide. While surgery and physical therapy are able to relieve cLBP for some, many continue to experience pain, which has led to an increased use of opioids. BACPAC will investigate biological and biopsychosocial mechanisms of cLBP using interdisciplinary methods and innovative technologies. One goal of the program will be to develop a holistic model of how various tissues and systems of the body interact to contribute to cLBP. Another goal is to develop and test individualized therapies for cLBP, including potentially combining drugs and non-pharmacologic approaches. The program will also create algorithms based on each patient’s unique symptoms, biology, and psychosocial factors to predict which therapies will work best for each individual. Ultimately, BACPAC is expected to improve clinical management of pain, with or without opioids.
More than 10 million people in the United States have osteoporosis, a disease defined by low bone mineral density that places people at risk of disabling and life-threatening fractures. Lifestyle changes, including exercise and a healthy diet, may help reduce a person’s risk of fracture. However, medications are often needed to prevent fractures if a person has osteoporosis and are essential if a person has experienced a previous fragility fracture. Rigorous clinical studies have demonstrated that 3 to 5 years of osteoporosis medication therapy prevents fractures. Clinical guidelines recommend bisphosphonates as a first line of treatment for most people who have osteoporosis, and approval of these medications and other societal changes are considered to be the cause of a dramatic decrease in hip fracture rates in the United States. However, reports of rare but serious adverse events and public concern about them have coincided with a marked decrease in the use of osteoporosis drugs and a leveling off of hip fracture rates. In October 2018, NIAMS, the National Institute on Aging (NIA), and the NIH Office of Disease Prevention hosted a Pathways to Prevention Workshop on the Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention to identify research gaps and suggest focus areas that could move the field forward. As part of the next steps, NIAMS and NIA agreed to work with other interested federal partners to explore near- and long-term opportunities to foster research related to this pressing public health need.
Capitalizing on recent investments
While new cancer immunotherapies have led to dramatic advances in the fight against cancer, the treatments also can be associated with a range of other effects on the immune system, including autoimmune responses. Over the past several years NIAMS has participated with the National Cancer Institute (NCI) and NIAID in supporting Cancer Moonshot funding opportunities to eliminate or reduce the severity of inflammatory and autoimmune side effects of cancer immunotherapy. For example, NIAMS and NCI currently support a study to identify pathways involved in immune-related cutaneous adverse reactions, which can cause cancer treatments to be interrupted or stopped. In 2018, NIAMS, NCI and NIAID began convening an annual conference on Cancer, Autoimmunity and Immunology to enable the exchange of findings and ideas for research on safer, more effective cancer immunotherapies and new insights into the mechanisms of autoimmunity.
Overall Budget Policy:
The FY 2022 President’s Budget request for NIAMS is $680.2 million, an increase of $45.9 million or 7.2 percent compared to the FY 2021 Enacted level. These increases are distributed across all programmatic areas including basic, epidemiological, or clinical research, with roughly half of the increase intended to enhance pain research across the NIAMS portfolio.
 Sebbag E, Felten R, Sagez F, Sibilia J, Devilliers H, Arnaud L. The world-wide burden of musculoskeletal diseases: a systematic analysis of the World Health Organization Burden of Diseases Database. Ann Rheum Dis. 2019;78(6):844-848. doi:10.1136/annrheumdis-2019-215142
 Blyth FM, Briggs AM, Schneider CH, Hoy DG, March LM. The Global Burden of Musculoskeletal Pain-Where to From Here? Am J Public Health. 2019;109(1):35-40. doi:10.2105/AJPH.2018.304747
 Luckhaupt SE, Dahlhamer JM, Gonzales GT, et al. Prevalence, Recognition of Work-Relatedness, and Effect on Work of Low Back Pain Among U.S. Workers. Ann Intern Med. 2019;171(4):301-304. doi:10.7326/M18-3602
 Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014 Nov;29(11):2520-6. doi: 10.1002/jbmr.2269. PMID: 24771492; PMCID: PMC4757905.
IC Fact Sheet [PDF]
History and Mission
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) was established in 1986. Its mission is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases.
Arthritis and musculoskeletal and skin conditions affect people of all ages and racial and ethnic backgrounds. Combined, they afflict tens of millions of Americans, cause tremendous human suffering, and cost the U.S. economy billions of dollars in health care costs and lost productivity. NIAMS aims to foster a rich and adaptable research environment that enables scientists to capitalize on opportunities as they arise and stimulate new areas that are unexpected and transformative.
Lindsey A. Criswell, M.D., M.P.H., D.Sc., became Director of NIAMS in February, 2021. Previously, she served as vice chancellor of research at the University of California, San Francisco, as well as professor of rheumatology, and professor of orofacial sciences. Her research focuses on the genetics and epidemiology of human autoimmune disease, particularly rheumatoid arthritis and systemic lupus erythematosus. She also has mentored many students and junior faculty to independent research careers.
Facts and Figures
In FY 2020, NIAMS supported:
- 219 full-time equivalent employment (FTE) positions
- 27 intramural principal investigators
- 727 extramural continuing RPG
- 275 extramural competing RPG
- 50 early-stage investigator awards
- 322 funded principal investigators
- 277 extramural full-time trainee positions
Highlights from NIAMS-Supported Research
- Basic research discoveries have led to new FDA-approved drugs for rheumatoid arthritis, X-linked hypophosphatemia (XLH), and other diseases.
ImageCredit Koehler lab, Nature
- An hour of moderate to vigorous physical activity each week is sufficient to stave off disability as people age.
- ACL (anterior cruciate ligament) knee surgery outcomes are better when using a graft from the patient, rather than from donor tissue.
Women with lupus often experience adverse pregnancy outcomes. NIAMS-funded researchers found a unique immune signature that appears to predict the development of preeclampsia more accurately than prediction models based on clinical factors alone. If verified, it could help physicians better manage high-risk patients with autoimmune diseases and improve prenatal care.
The Osteoarthritis Initiative, a public-private partnership, has assembled the largest and perhaps most important datasets in the history of OA research. These datasets are facilitating development of drugs that interrupt the underlying disease processes by providing objective and measurable standards for disease progression.
- NIAMS intramural researchers have quickly pivoted their programs to address the COVID-19 pandemic. Programs are working to develop new — or adapt existing — therapeutics for patients with COVID and to identify novel approaches to prevent SARS-CoV-2 infection.
- NIAMS and partners hosted a Pathways to Prevention Workshop on the Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention in FY 2019. Ongoing activities are encouraging research to explore why rare conditions like atypical femoral fracture and osteonecrosis of the jaw occur in some patients taking bone antiresorptive medications such as bisphosphonates.
- The Accelerating Medicines Partnership in rheumatoid arthritis (RA) and lupus is adapting cutting-edge, high-throughput technologies to analyze single immune and tissue cells from organs affected by RA and lupus. Researchers are identifying biological pathways that may become drug targets for treating autoimmune diseases.
- Optimizing Cell-Based Clinical Trials to Treat Knee Osteoarthritis: Clinical use of biologics to treat orthopaedic conditions has greatly outpaced the evidence. Often in clinics around the globe and in the United States, patients ask for and surgeons offer largely unproven treatments. In FY 2022, NIAMS plans to explore ways research can improve and accelerate the clinical evaluation, use, and optimization of cell-based biologics for knee OA.
- Understanding Gene-Microbiome Connections: Both a person’s genetics and their microbiome—the microbes living in and on the body—are considered to be important contributing factors to a variety of diseases. While often studied separately, in FY 2022 NIAMS plans to convene a meeting to explore potential synergies between them that may be key to understanding the pathogenesis of many diseases and conditions.
- Unraveling Chronic Inflammation Resolution: Chronic inflammation is a common pathogenic element among many diseases within the NIAMS mission. Understanding how inflammation is resolved could lead to innovative ways to treat chronic inflammatory diseases. In FY 2022, NIAMS plans to hold a roundtable to stimulate research in this area.
Major Changes in the Fiscal Year 2022 President’s Budget Request
Major changes by budget mechanism and/or budget activity detail are briefly described below. Note that there may be overlap between budget mechanism and activity detail, and these highlights will not sum to the total change for the FY 2022 President’s Budget request for NIAMS, which is $680.2 million, an increase of $45.9 million from the FY 2021 Enacted level. Within this funding level, NIAMS will pursue its highest research priorities through strategic investments and careful stewardship of appropriated funds.
Research Project Grants (RPGs) (+$31.6 million; total $455.4 million):
NIAMS will support a total of 1,108 Research Project Grant (RPG) awards in FY 2022. Noncompeting awards will increase by $4.2 million. Competing RPGs will increase by 70 awards and $25.6 million. Roughly half of the proposed budget increase for NIAMS is intended to enhance the Institute’s research efforts to understand the underlying mechanisms of pain, which may lead to the development of safer, non-addictive interventions for pain, and thereby reduce the need for opioids. NIAMS continues to place a priority on support to early-stage investigators.
Other Research (+$2.9 million; total $27.5 million):
NIAMS will support a total of 179 Other Research awards in FY 2022. Research Careers will increase by 22 awards and $2.9 million from the FY 2021 Enacted level.
Intramural Research (+$6.5 million; total $74.0 million):
NIAMS will increase funding for intramural research by 9.6 percent. These increases are distributed across all programmatic areas and basic, translational or clinical research.
|MECHANISM||FY 2020 Final||FY 2021 Enacted||FY 2022 President's Budget||FY 2022
FY 2021 Enacted
|Research Project Grants||1,038||$419,456||1,062||$423,803||1,108||$455,382||46||$31,579|
|Research Centers in Minority Institutions||0||0||0||0||0||0||0||0|
|Cooperative Clinical Research||0||0||0||0||0||0||0||0|
|Biomedical Research Support||0||0||0||0||0||0||0||0|
|Minority Biomedical Research Support||0||250||0||250||0||250||0||0|
|Total Research Grants||1,241||$488,562||1,261||$492,614||1,326||$527,065||65||$34,451|
|Ruth L Kirschstein Training Awards:||FTTPs||FTTPs||FTTPs||FTTPs|
|Total Research Training||277||$16,986||277||$17,320||277||$17,909||0||$589|
|Research & Develop. Contracts||39||$19,631||42||$21,263||42||$24,245||0||$2,982|
|Res. Management & Support||105||34,714||114||35,533||114||36,954||0||1,421|
|SBIR Admin. (non-add)||(0)||(0)||(0)||(0)||(0)||(0)||(0)||(0)|
|Buildings and Facilities||0||0||0||0|
1All items in italics and brackets are non-add entries.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
For carrying out section 301 and title IV of the PHS Act with respect to arthritis and musculoskeletal and skin diseases, [$634,292,000]$680,186,000.
|FY 2021 Enacted||$634,286|
|FY 2022 President's Budget||$680,186|
|FY2021 Enacted||FY 2022 President's Budget||Built-In Change from FY 2021 Enacted|
|CHANGES||FTEs||Budget Authority||FTEs||Budget Authority||FTEs||Budget Authority|
|1. Intramural Research:|
|a. Annualization of January 2021 pay increase & benefits||$21,072||$21,700||$57|
|b. January FY 2022 pay increase & benefits||21,072||21,700||571|
|c. Paid days adjustment||21,072||21,700||0|
|d. Differences attributable to change in FTE||21,072||21,700||0|
|e. Payment for centrally furnished services||12,115||12,720||606|
|f. Cost of laboratory supplies, materials, other expenses, and non-recurring costs||34,369||39,592||939|
|2. Research Management and Support:|
|a. Annualization of January 2021 pay increase & benefits||$18,919||$19,495||$50|
|b. January FY 2022 pay increase & benefits||18,919||19,495||526|
|c. Paid days adjustment||18,919||19,495||0|
|d. Differences attributable to change in FTE||18,919||19,495||0|
|e. Payment for centrally furnished services||3,897||4,092||195|
|f. Cost of laboratory supplies, materials, other expenses, and non-recurring costs||12,716||13,367||430|
|FY2021 Enacted||FY 2022 President's Budget||Program Change from FY 2021 Enacted|
|1. Research Project Grants:|
|2. Research Centers||42||$44,217||39||$44,217||-3||$0|
|3. Other Research||157||24,594||179||27,466||22||2,872|
|4. Research Training||277||17,320||277||17,909||0||589|
|5. Research and development contracts||42||21,263||42||24,245||0||2,982|
|6. Intramural Research||124||$67,556||124||$74,013||0||$4,284|
|7. Research Management and Support||114||35,533||114||36,954||0||221|
|9. Buildings and Facilities||0||0||0|
|Total built-in and program changes||$45,900|
Fiscal Year 2022 Budget Graphs
History of Budget Authority and FTEs:
Distribution by Mechanism:
Change by Selected Mechanism:
|FY 2020 Final||FY 2021 Enacted||FY 2022 President's Budget||FY 2022
FY 2021 Enacted
|Systemic Rheumatic and Autoimmune Diseases||$106,227||$107,444||$115,134||$7,691|
|Skin Biology and Diseases||101,532||102,696||110,047||7,351|
|Muscle Biology and Diseases||80,979||81,907||87,770||5,863|
|Joint Biology and Diseases and Orthopaedics||155,995||157,782||169,076||11,294|
|Bone Biology and Diseases||80,446||81,368||87,192||5,824|
|Research Management & Support||105||$34,714||114||$35,533||114||$36,954||0||$1,421|
1Includes FTEs whose payroll obligations are supported by the NIH Common Fund.
Justification of Budget Request
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Authorizing Legislation: Section 301 and title IV of the Public Health Service Act, as amended.
Budget Authority (BA):
FY 2020 Final
FY 2022 President's Budget
FY 2022 +/- FY 2021
Program funds are allocated as follows: Competitive Grants/Cooperative Agreements; Contracts; Direct Federal/Intramural and Other.
Systemic Rheumatic and Autoimmune Diseases
This program supports basic, translational, and clinical research on immune-mediated arthritis and autoimmune-related acute and chronic disorders in adults and children. For example, NIAMS is supporting research on joint cells called fibroblasts that contribute to inflammation in RA. Current RA therapies target immune cells, so anti-fibroblast therapies would represent a new approach for modifying disease course. A NIAMS-funded study of cells from RA patients identified two critical molecules in fibroblasts that mediate response to proinflammatory molecules and the subsequent production of factors necessary for recruiting immune cells. Further studies could explore whether those two regulators are potential therapeutic targets for RA treatment.
Researchers working on innovative ways to alleviate RA pain are exploring why many people with RA experience pain despite taking anti-inflammatory drugs. While pain early after the development of RA is linked to joint inflammation, NIAMS-supported scientists explored whether chronic pain in established RA could be linked to both inflammatory and non-inflammatory causes. Using a mouse model of inflammatory arthritis, they discovered that immune complexes generated in RA trigger arthritis pain via an inflammation-independent mechanism, at least in part, through direct activation of a receptor on the surface of sensory neurons in the joints. The finding provides a new direction for research on treatments for arthritis pain.
Researchers also continue to advance understanding of the relationship between lung diseases and RA. A prospective study in two large cohorts of women showed that individuals with asthma and chronic obstructive pulmonary disease, commonly called COPD, were more likely to develop RA than those without lung disease, implicating the lung conditions as an RA risk factor. The results are consistent with previous reports that mucosal surfaces of the lung may be one of the first places that RA develops with autoantibodies being formed at these sites years before joint symptoms appear. The findings may inform the clinical care of asthma and COPD patients, allow early detection of RA in those patients, and lower of the risk of negative long-term health outcomes.
The FY 2022 budget estimate for this program is $115.1 million, an increase of $7.7 million or 7.2 percent compared to the FY 2021 Enacted level. In FY 2022, NIAMS will continue participation in a Notice of Special Interest to promote fundamental and applied research on inflammation resolution. While acute inflammation protects the body from infection, injury, and chemical exposures, excessive and uncontrolled chronic inflammation can cause tissue damage and contribute to the development of diseases such as rheumatoid arthritis, lupus, scleroderma, psoriasis, osteoporosis, osteoarthritis, and chronic back pain. NIAMS also plans to hold an FY 2022 roundtable meeting on the relationship between inflammation resolution and chronic inflammatory diseases within the NIAMS mission. The meeting will bring together key experts to exchange ideas, discuss areas of potential collaboration, and identify unmet research needs.
Skin Biology and Diseases
This program funds basic, translational, and clinical research in skin, including investigations of the basic and developmental biology of skin and studies of skin as an immune, sensory, endocrine, and metabolic organ. Studying interactions between skin and other organs and structures is increasingly important for advancing knowledge of health and disease. A recent study of skin inflammation revealed that overexpression of a protein called kallikrein-related peptidase 6 in the skin of mice promotes both psoriasis-like lesions and progressive peripheral joint inflammation resembling a severe form of arthritis, called psoriatic arthritis, that develops in some people with psoriasis. The finding reveals a potential new therapeutic target for psoriatic arthritis and demonstrates how research in one tissue can yield important discoveries in diseases affecting another.
The program also plays an important role in creating innovative model systems to explore disease mechanisms and evaluate potential therapies. Researchers supported by NIAMS developed a new mouse model of melanoma, a dangerous form of skin cancer that develops from skin pigment-producing melanocyte cells. In previous mouse models, melanoma first appears in the skin dermis, whereas in the new model the cancer develops in the skin epidermis, the same location where human melanoma arises. The new model will help improve understanding of the biology of this deadly type of skin cancer and provide new ideas about how to counter it. Other investigators have developed an engineered skin model in the laboratory using human stem cells. This model improves on previous engineered skin equivalents in that it develops both the upper and lower skin layers and contains many specialized structures found in skin, like hair, fat, and nerves.
Skin health and function are influenced by the internal and external environment, including factors such as the immune system and microbes in and on the body. A NIAMS-funded study showed that feeding mice a Western diet, which is high in fat and simple sugar, results in skin inflammation mediated by γδT immune cells. The result supports the idea that environmental cues, such as a high fat diet, directly influence the condition of the skin. Although the mechanisms by which the Western diet activates γδT cells leading to dermatitis in mice are unknown, the finding provides a new direction for research to explore, such as whether the effect is related to diet-induced alterations to the gut microbiome.
The FY 2022 budget estimate for this program is $110.0 million, an increase of $7.4 million or 7.2 percent compared to the FY 2021 Enacted level. In FY 2022, the program will seek to accelerate research focused on describing how gene-microbiome interactions may impact diseases and conditions within the NIAMS mission by hosting a meeting of experts in relevant disciplines. An animal’s genetics and the composition of the microbes in its body are considered important factors that contribute to a variety of pathologies. However, “host” genetics and the microbiome are typically studied separately, so the relationship between them is poorly understood. The meeting will explore possible synergy between an organism’s own genetics and its microbiome as a potential key to understanding the pathogenesis of skin diseases and conditions.
Muscle Biology and Diseases
This program’s overarching objective is to explain muscle’s role in health and, ultimately, to treat or prevent skeletal muscle diseases and disorders such as the muscular dystrophies, muscle ion channel diseases, inflammatory myopathies, disuse atrophy, skeletal muscle injury, and loss of muscle mass and strength associated with aging and diseases. For example, investigators recently defined a pathway involved in a muscle wasting phenomenon associated with cancer, called cachexia, in people and in mice. They showed that manipulating this pathway in mice blunts the muscle wasting phenomenon and may suggest future therapeutic approaches for patients.
Muscular dystrophies are an area of emphasis within the NIAMS muscle research portfolio. One recent advance demonstrated that a U.S. Food and Drug Administration (FDA)-approved drug for heart disease shows promise in clinical trials for treating cardiomyopathy in Duchenne muscular dystrophy (DMD). The latest findings suggest that this drug family also might be adapted to treat the skeletal muscle damage that is seen in people who have DMD. Other work uncovered two possible interventions—one based on small molecules called peptides, the other using monoclonal antibodies—that improve certain measurable muscle parameters in a mouse model of DMD. In the future, researchers and clinicians may be able to apply these findings to improve care and quality of life for individuals with DMD.
The FY 2022 budget estimate for this program is $87.8 million, an increase of $5.9 million or 7.2 percent compared to the FY 2021 Enacted level. Program plans for FY 2022 include support for two Senator Paul D. Wellstone Muscular Dystrophy Research Centers that promote collaborative basic, translational, and clinical research and provide important resources that can be used by muscular dystrophy researchers nationwide. Currently, one center is developing reagents, measurements, and clinical trial methods and infrastructures to speed the development of therapies for DMD and facioscapulohumeral muscular dystrophy (FSHD). The second will be a new award anticipated to be made in FY 2021.
Bone Biology and Diseases
This program supports studies on the control of bone remodeling (bone formation, bone resorption) and mineralization, as well as the effects of hormones, growth factors, and other signaling molecules on bone cells. The Institute has overseen several large epidemiologic cohorts to characterize the natural history of osteoporosis and identify genetic and environmental risk factors that contribute to fracture. NIAMS also supports clinical trials to test the effectiveness of interventions to prevent fractures associated with osteoporosis and other metabolic bone diseases. For example, the Denosumab and Teriparatide Administration (DATA) study demonstrated greater increases in hip and spine bone mineral density (BMD) in post-menopausal women treated with combination therapy versus standard doses of denosumab (an anti-resorptive drug that inhibits bone resorption) and teriparatide (an anabolic drug that promotes bone formation). Following the positive results of the DATA study, investigators demonstrated that increases in BMD are even greater with a higher dose of the anabolic therapy combined with denosumab.
The Bone Biology and Diseases program also supports research on the causes, pathophysiology, and treatment of a wide range of developmental disorders of the skeleton, many of which are genetic, and less common bone diseases, such as autosomal dominant hypophosphatemic rickets (ADHR). Standard management of ADHR consists of vitamin D and phosphate therapies, which can have undesirable side effects. Recently, researchers demonstrated that low dose oral iron, which is low cost and safe, can treat and prevent disease manifestations of ADHR in patients.
The FY 2022 budget estimate for this program is $87.2 million, an increase of $5.8 million or 7.2 percent compared to the FY 2021 Enacted level. This program is leading the Institute’s efforts described in the Director’s Overview related to the Pathways to Prevention Workshop on the Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention. Plans for FY 2022 include a shared effort with NIA, the National Institute of Dental and Craniofacial Research, and the NIH Office of Research on Women’s Health to encourage researchers to explore the mechanisms leading to the rare conditions atypical femoral fracture and osteonecrosis of the jaw, which are associated with bone anti-resorptive medications, such as bisphosphonates.
The Osteoarthritis Initiative:
A Public-Private Partnership to Advance Biomarker Discovery
Osteoarthritis (OA) is the most common type of arthritis. It occurs when the tissue that covers the ends of bones in a joint is damaged, which allows the bones to rub together leading to pain, swelling, and loss of motion. A limited number of therapies exist for OA. One barrier to the development of drugs that interrupt the underlying disease processes is a lack of objective and measurable standards for disease progression. To overcome this problem, NIAMS, along with NIA, led the development of the Osteoarthritis Initiative (OAI), a nationwide, multicenter observational study to follow people who either have or are at risk for developing knee OA. This public-private partnership began more than a decade ago to gather and catalog longitudinal findings from nearly 5,000 people with OA and healthy people.
Participant visits through 8 years of follow-up have been completed, which makes the OAI one of the largest and perhaps most important datasets in the history of OA research. The dataset contains clinical, genomic, patient-reported, and functional data; biological specimens; and X-ray and magnetic resonance images. The data are freely available at oai.nih.gov. Investigators can use this unique repository to track the natural history of knee OA across the complete spectrum of disease. To date, more than 680 peer-reviewed papers have been published using OAI data and, in 2020, the FDA accepted three Letters of Intent related to the qualification of biomarkers to advance drug development tools for OA.
As NIAMS looks to FY 2022, researchers will have opportunities to examine OAI data to develop hypotheses about possible biomarkers of disease onset and progression, test their theories, describe the natural history of OA, and investigate factors that influence disease development and severity. In addition, OAI data can serve as a novel resource for investigators with computational and machine learning expertise in other fields to apply big data methodologies to biomedical research.
Joint Biology and Diseases and Orthopaedics
This program funds a broad spectrum of basic, translational, and clinical research centered on the interplay among the body’s muscles, bones, and connective tissues. It includes research on the biology, structure, and function of joints and surrounding tissues and the application of this knowledge to a variety of diseases and conditions. For example, researchers demonstrated that long-term inflammation weakens the intervertebral discs that pad the bones of the spine and predisposes the discs to herniation.
The program also funds research on molecular biology to understand the mechanisms of joint tissue formation and defects thereof; imaging to improve diagnosis and treatment of bone and joint disorders; and tissue engineering and regenerative medicine to facilitate repair of damage caused by trauma to otherwise healthy tissue. Several regenerative medicine projects relate to repairing large gaps in bone or cartilage, which can occur during traumatic injuries such as those seen in automobile crashes or on the battlefield. In one recent paper, researchers used advanced 3-D printing technology with ceramic and demineralized bone matrix materials as “paint” to promote spinal fusion in a rat model. The results demonstrated a 92 percent fusion rate without the need for additional growth factors. In another project, investigators developed a synthetic biodegradable fiber mesh to promote better integration of cartilage grafts with host tissue.
At the clinical end of the research continuum, the program focuses on treatment and prevention of acute and chronic bone and joint injuries and orthopaedic conditions including musculoskeletal pain. Recently, a study comparing the outcomes of two common treatments for hip fracture (hemiarthroplasty, which is a partial replacement of only the femoral head with a prosthesis, and total hip arthroplasty where all joint parts are replaced) showed that while the need for additional surgery on the injured hip within two years of the original procedure did not differ significantly between the groups, total hip arthroplasty was associated with modestly better function but a slightly higher incidence of serious adverse events. When it comes to total knee replacement as a treatment for end-stage osteoarthritis (OA), analysis of a large regional database revealed that African American patients were more likely than Whites to be discharged to an inpatient or skilled nursing facility after their procedure and to be readmitted to an acute care hospital within 90 days. The authors did not have a definitive explanation for this disparity in care and outcomes, but speculated that the reasons are likely multi-factorial and may involve patient-, clinician-, and system-level factors including socioeconomic disparities, patient preference, co-occurring conditions, health literacy, and the patient-physician relationship.
The FY 2022 budget estimate for this program is $169.1 million, an increase of $11.3 million or 7.2 percent compared to the FY 2021 Enacted level. Disparities in discharge status following total knee replacement for end-stage OA (described above) is one of several known differences in OA treatment outcomes that vary among race, ethnicity, and socioeconomic status. Inequalities in access to care also have been documented in diverse populations. Program plans for FY 2022 include building on an FY 2021 workshop that will evaluate health equity in OA with a key focus on current issues surrounding health disparities and related research gaps. Other plans for FY 2022 include exploring ways to improve and accelerate the clinical evaluation, use, and optimization of cell-based therapies for knee OA.
Intramural Research Program
The NIAMS Intramural Research Program (IRP) conducts innovative basic, translational, and clinical research relevant to the NIAMS mission and trains investigators who are interested in related careers. Its basic researchers and physician-scientists study the genetics, etiology, pathogenesis, and treatment of rheumatic, autoimmune, inflammatory, bone, skin, and muscle diseases.
One of the unique features of the IRP is the ability to quickly pivot research programs and staff to address scientific needs and take advantage of opportunities. This was clearly demonstrated during the emergence of the COVID-19 pandemic. NIAMS intramural researchers were able to build on the technologies and expertise already within the program and contribute to the global fight against the disease. For example, NIAMS intramural researchers were designing “nanobodies” to protect people from human immunodeficiency virus (HIV) infection. Nanobodies are similar to the antibodies humans produce in response to most infections. They naturally occur in some mammal species, such as camels, llamas, and alpacas, and NIAMS researchers were already working on technologies to develop nanobodies from mice. The researchers applied their knowledge and approach to the SARS-CoV-2 virus and generated nanobodies that are highly specific to the SARS-CoV-2 spike protein. They are continuing to explore whether monoclonal nanobodies, derived from mice or llamas, could be developed into a prophylactic treatment to prevent COVID-19 in humans. Another NIAMS intramural group is working to develop new therapeutics that will disable viral proteins and prevent propagation of the virus. For coronavirus, an essential step in viral propagation is to replicate its RNA in the host cell and suppress expression of host mRNA. The sophisticated system for RNA replication and transcription is unique for coronavirus. Researchers aim to exploit this pathway to develop an antiviral treatment. Eventually, a therapeutic based on this approach would target the RNA of the virus and potentially represent a universal coronavirus medication.
Identifying the Genetic Cause of a Rare Bone Disease
Melorheostosis is a rare, progressive disease that affects the growth and development of bone and soft tissue. Characterized by the thickening and widening of bone, individuals with melorheostosis often experience pain, deformity, and a limited range of movement. Although the underlying causes of this serious and debilitating condition have long remained unknown, recent collaborative work led by the NIAMS IRP Clinical and Investigative Orthopaedics Surgery Unit uncovered a genetic cause of melorheostosis—a finding with far-reaching implications for other bone-related diseases.
Researchers at the NIH were able to work with 15 people with melorheostosis from around the world who traveled to the NIH Clinical Center to undergo biopsies of affected and unaffected bones. In doing so, the collaborative team of researchers from multiple Institutes discovered a genetic mutation in a crucial pathway for skeletal development. This mutation caused bone cells to display increased growth and hardening in affected bones. Though this finding represents a critical advance in understanding the progression of melorheostosis, it is only the latest genetic mutation NIAMS researchers have uncovered as a cause of this rare disease.
As a result of NIH’s continued work in this area, researchers can now further investigate two, novel genetic targets present in melorheostosis-affected bone. In addition to providing new insights into this condition, these findings have implications for other diseases that impact broader populations. For example, as individuals age, bones can experience weakening, which is the opposite of what occurs in affected bones of people with melorheostosis. Uncovering genetic mutations involved in bone growth provides researchers with a potential pathway that could be harnessed by future therapeutics addressing the deleterious effects of aging on bone.
NIAMS intramural scientists continue to make progress in understanding the inner workings of the immune system and how this can contribute to, or protect against, disease. For example, it is becoming clear that the microbiota—the variety of commensal microbes (bacteria, viruses, fungi) that inhabit the skin surface—is involved in maintaining healthy immunity and in driving disease pathology. In one intramural study, researchers identified how a subset of immune cells, called innate lymphoid cells, are localized to and sustained in skin by signaling factors produced by hair follicles. These findings provide a better understanding of how a mutually beneficial relationship with the microbiota is maintained and future studies will explore how communication between the microbiota and immune system may be altered in disease. Another research group is defining the immune system differences observed between men and women. Earlier work has shown that females mount more robust immune responses than males. Such responses can be beneficial, contributing to better recovery from infections or response to vaccination, or detrimental, leading to higher risk of autoimmune disease. In a recent study, intramural researchers characterized the differences in gene expression between neutrophils—an important immune cell subset—from healthy males and females. They demonstrated that many of the differences in maturity and responsiveness of neutrophils are likely driven by sex hormones. In the future, this knowledge may allow clinicians to better tailor treatment plans to create individualized, sex-specific therapeutic approaches.
The FY 2022 budget estimate for this program is $74.0 million, an increase of $6.5 million or 9.6 percent compared to the FY 2021 Enacted level. Program plans for FY 2022 include continued support for basic and clinical investigations into the causes and treatment of rheumatic, skin, muscular, and inflammatory diseases. In particular, the IRP plans capitalize on recent high-performance computing capabilities by incorporating new technologies to drive scientific discovery. For example, the program will enhance clinical research by expanding genomic sequencing capabilities within the Translational Immunology Section to increase capacity to identify somatic mutations that lead to autoimmunity. Additionally, the program plans to incorporate improved microscopy technologies, such as novel cryo-electron microscopy, super-resolution microscopy, and light-sheet microscopy, into the program.
Research Management and Support
The RMS budget supports the scientific, administrative management, and information technology activities associated with NIAMS’ day-to-day operations. In FY 2020, NIAMS managed 1,241 research grants and centers, as well as 39 research and development contracts and 277 individual and institutional full-time research training positions. NIAMS supported 580 clinical research studies, including 101 clinical trials. Also, in FY 2020 NIAMS developed a series of informational one-page papers summarizing key elements presented in the Institute’s Strategic Plan for FYs 2020-2024. These “About Our Strategic Plan” documents provide concise, lay-friendly summaries of promising research avenues throughout the NIAMS mission areas. They are designed to be shared with, among others, researchers, healthcare professionals, and patient and voluntary organizations. Each document focuses on a different component of the NIAMS portfolio along with four broad cross-cutting scientific themes that highlight the increasing convergence of scientific knowledge and approaches across fields. In addition, NIAMS launched several new communication channels in FY 2020 to share information about funding opportunities with the extramural research community. Through a monthly newsletter and dedicated Twitter page, NIAMS hopes to maximize its outreach to scientists who may be outside the usual NIAMS audiences and engage more researchers to explore topics of relevance to the NIAMS mission.
The FY 2022 budget estimate for this program is $37.0 million, an increase of $1.4 million or 4.0 percent compared to the FY 2021 Enacted level. Program plans for FY 2022 include continued activities to support the NIH Anti-Harassment efforts managed by the NIH Civil Program. Specifically, NIAMS has developed a comprehensive Anti-Harassment Outreach Plan to provide, and increase awareness of, resources to help prevent and address harassment in the workplace. As part of the Outreach Plan, NIAMS created the NIAMS Culture Committee, a diverse group of staff from across the Institute that will counsel leadership on policies and programs to promote a culture of civility, diversity and inclusion, and all other factors that impact organizational climate.
|Fiscal Year||Budget Estimate to Congress||House Allowance||Senate Allowance||Appropriation|
1Budget Estimate to Congress includes mandatory financing.
|Source of Funding||FY 2020 Final||FY 2021 Enacted||FY 2022 President's Budget|
|OAR HIV/AIDS Transfers||0||-6||0|
|Subtotal, adjusted budget authority||$624,889||$634,286||$680,186|
|Unobligated balance, start of year||0||0||0|
|Unobligated balance, end of year||0||0||0|
|Subtotal, adjusted budget authority||$624,889||$634,286||$680,186|
|Unobligated balance lapsing||-57||0||0|
1 Excludes the following amounts (in thousands) for reimbursable activities carried out by this account:
FY 2020 - $8,364 FY 2021 - $8,489 FY 2022 - $8,702
|FY 2021 Enacted||FY 2022 President's Budget||FY 2022
FY 2021 Enacted
|Total compensable workyears:|
|Full-time equivalent of overtime and holiday hours||0||0||0|
|Average ES salary||$199||$205||$5|
|Average GM/GS grade||12.7||12.7||0.0|
|Average GM/GS salary||$122||$126||$4|
|Average salary, Commissioned Corps (42 U.S.C. 207)||$107||$110||$3|
|Average salary of ungraded positions||$146||$150||$4|
|OBJECT CLASSES||FY 2021 Enacted||FY 2022 President's Budget||FY 2022
|11.3||Other Than Full-Time Permanent||8,814||9,014||201|
|11.5||Other Personnel Compensation||993||1,015||23|
|11.8||Special Personnel Services Payments||2,402||2,457||55|
|11.9||Subtotal Personnel Compensation||$30,179||$30,866||$688|
|12.1||Civilian Personnel Benefits||9,636||10,147||512|
|12.2||Military Personnel Benefits||177||181||5|
|13.0||Benefits to Former Personnel||0||0||0|
|Subtotal Pay Costs||$39,991||$41,195||$1,204|
|21.0||Travel & Transportation of Persons||41||248||207|
|22.0||Transportation of Things||111||125||13|
|23.1||Rental Payments to GSA||0||0||0|
|23.2||Rental Payments to Others||0||0||0|
|23.3||Communications, Utilities & Misc. Charges||330||369||39|
|24.0||Printing & Reproduction||0||0||0|
|25.3||Purchase of goods and services from government accounts||43,030||48,163||5,134|
|25.4||Operation & Maintenance of Facilities||116||121||5|
|25.7||Operation & Maintenance of Equipment||7,584||8,764||1,180|
|25.8||Subsistence & Support of Persons||0||0||0|
|25.0||Subtotal Other Contractual Services||$83,173||$93,000||$9,827|
|26.0||Supplies & Materials||4,025||4,764||739|
|32.0||Land and Structures||59||61||2|
|33.0||Investments & Loans||0||0||0|
|41.0||Grants, Subsidies & Contributions||501,588||534,616||33,028|
|42.0||Insurance Claims & Indemnities||0||0||0|
|43.0||Interest & Dividends||0||0||0|
|Subtotal Non-Pay Costs||$594,295||$638,991||$44,696|
|Total Budget Authority by Object Class||$634,286||$680,186||$45,900|
1Includes FTEs whose payroll obligations are supported by the NIH Common Fund.
|OBJECT CLASSES||FY 2021 Enacted||FY 2022 President's Budget||FY 2022
|Full-Time Permanent (11.1)||$17,759||$18,163||$404|
|Other Than Full-Time Permanent (11.3)||8,814||9,014||201|
|Other Personnel Compensation (11.5)||993||1,015||23|
|Military Personnel (11.7)||211||217||6|
|Special Personnel Services Payments (11.8)||2,402||2,457||55|
|Subtotal Personnel Compensation (11.9)||$30,179||$30,866||$688|
|Civilian Personnel Benefits (12.1)||$9,636||$10,147||$512|
|Military Personnel Benefits (12.2)||177||181||5|
|Benefits to Former Personnel (13.0)||0||0||0|
|Subtotal Pay Costs||$39,991||$41,195||$1,204|
|Travel & Transportation of Persons (21.0)||$41||$248||$207|
|Transportation of Things (22.0)||111||125||13|
|Rental Payments to Others (23.2)||0||0||0|
|Communications, Utilities & Misc. Charges (23.3)||330||369||39|
|Printing & Reproduction (24.0)||0||0||0|
|Other Contractual Services:|
|Consultant Services (25.1)||20,502||21,909||1,406|
|Other Services (25.2)||6,517||7,233||716|
|Purchases from government accounts (25.3)||25,959||29,360||3,401|
|Operation & Maintenance of Facilities (25.4)||116||121||5|
|Operation & Maintenance of Equipment (25.7)||7,584||8,764||1,180|
|Subsistence & Support of Persons (25.8)||0||0||0|
|Subtotal Other Contractual Services||$60,678||$67,387||$6,709|
|Supplies & Materials (26.0)||$4,025||$4,764||$739|
|Subtotal Non-Pay Costs||$65,186||$72,892||$7,706|
|Total Administrative Costs||$105,177||$114,088||$8,911|
|OFFICE/DIVISION||FY 2020 Final||FY 2021 Enacted||FY 2022 President's Budget|
|Division of Extramural Research|
|Intramural Research Program|
|Office of the Director|
|Includes FTEs whose payroll obligations are supported by the NIH Common Fund.|
|FTEs supported by funds from Cooperative Research and Development Agreements.||0||0||0||0||0||0||0||0||0|
|FISCAL YEAR||Average GS Grade|
|GRADE||FY 2020 Final||FY 2021 Enacted||FY 2022 President's Budget|
|Total, ES Positions||0||1||1|
|Total, ES Salary||0||199,300||204,681|
|Commissioned Corps (42 U.S.C. 207)|
|Assistant Surgeon General||0||0||0|
|Senior Assistant Grade||0||0||0|
|Total permanent positions||165||178||178|
|Total positions, end of year||240||259||259|
|Total full-time equivalent (FTE) employment, end of year||219||238||238|
|Average ES salary||0||199,300||204,681|
|Average GM/GS grade||12.7||12.7||12.7|
|Average GM/GS salary||121,670||122,505||126,205|
1Includes FTEs whose payroll obligations are supported by the NIH Common Fund.