June 5, 2019


June 5, 2019
8:30 a.m. to 3:00 p.m.

June 5th, 2019 Webcast


The 98th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on June 5, 2019, at the National Institutes of Health (NIH) Campus, Building 45, Conference Rooms E1/E2. The meeting was chaired by Dr. Robert H. Carter, Acting Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).


Council members present:

Ms. Karen M. Ball, President and CEO, The Sturge-Weber Foundation*
Dr. Joan M. Bathon, Professor and Chief of the Division of Rheumatology, Columbia University College of Physicians and Surgeons*
Dr. Jill P. Buyon, Director, Division of Rheumatology, Department of Medicine, New York School of Medicine, and Director, NYU Lupus Center
Ms. Magdalena Castro-Lewis, Former Vice President for Programs, National Alliance of Hispanic Health
Dr. Elizabeth H. Chen, Professor, University of Texas Southwestern Medical Center*
Mr. Vincent Del Gaizo, Director of Strategic Partnerships and Patient Engagement, Childhood Arthritis and Rheumatology Research Alliance (CARRA)
Dr. Michael Econs, Glenn W. Irwin, Jr., Professor of Endocrinology and Metabolism; Director, Division of Endocrinology and Metabolism; and Professor of Medicine and Medical and Molecular Genetics, Indiana University School of Medicine
Dr. Said A. Ibrahim, Vice Chair for Strategy and Development and Chief, Division of Healthcare Delivery Science and Innovation, Department of Healthcare Policy and Research, Weill Cornell Medicine*
Dr. Judith A. James, Chair and Member, Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation
Dr. Ethan A. Lerner, Associate Professor of Dermatology, Massachusetts General Hospital
Ms. Rosemary J. Markoff, Co-Chair, Scleroderma Foundation National Advocacy Committee
Mr. William J. Mulvihill, The Mulvihill Advisory Group
Dr. Anthony Oro, Eugene and Gloria Bauer Professor of Dermatology, Associate Director and Professor, Center for Definitive and Curative Medicine, Department of Dermatology, Stanford University School of Medicine
Dr. Stephen J. Tapscott, Professor, Fred Hutchinson Cancer Research Center
Dr. Jennifer J. Westendorf, Margaret Amini Professor of Orthopaedic Regenerative Medicine Research, Mayo Clinic*
Dr. Michael J. Yaszemski, Professor, Orthopaedic Surgery and Biomedical Engineering, Mayo Clinic

* Ad Hoc Members

Staff and Guests

The following NIAMS staff and guests attended:


Mr. Steve Austin
Ms. Pamela Beheler
Dr. Alexey Belkin
Ms. Elizabeth Bouras
Dr. Amanda Boyce
Dr. Nakia Brown
Dr. Stephanie Burrows
Ms. Cindy Caughman
Dr. Ricardo Cibotti
Ms. Teresa Do
Dr. Jonelle Drugan
Ms. Colleen Dundas
Mr. Erik Edgerton
Ms. Jana Eisenstein
Mr. Folly Folivi
Dr. Yasuko Furumoto
Dr. Nancy Garrick
Ms. Shannon Griffin
Ms. Aleisha James
Mr. Andrew Jones
Dr. Anthony Kirilusha
Ms. Stephanie Kreider
Ms. Jane Lee

Dr. Gayle Lester
Dr. Helen Lin
Ms. Leslie Littlejohn
Dr. Kan Ma
Dr. Marie Mancini
Mr. Christopher Nee
Ms. Melinda Nelson
Dr. Kristy Nicks
Dr. Heiyoung Park
Mr. Rick Phillips
Dr. Marisol Pintucci
Ms. Trish Reynolds
Dr. Kathy Salaita
Ms. Robyn Strachan
Dr. James Taylor
Ms. Jamie Thompson
Dr. Carol Torgan
Dr. Hung Tseng
Dr. Fei Wang
Dr.Charles Washabaugh
Dr. Ted Zhang


Dr. Helene Langevin, Director, National Center for Complementary and Integrative Health (NCCIH)


A motion was made, seconded, and passed to approve the minutes of the 97th NAMSAC meeting, held on February 5, 2019.


Future Council meetings are currently planned for the following dates:

September 10, 2019
February 4, 2020
June 9, 2020
September 1, 2020

IV. Directors Report

Dr. Carter welcomed five new ad hoc members to the NIAMS Advisory Council: Ms. Karen Ball, Dr. Joan Bathon, Dr. Elizabeth Chen, Dr. Said Ibrahim, and Dr. Jennifer Westendorf. He also noted that this is the last meeting for Ms. Magdalena Castro-Lewis, and he thanked her for her service on behalf of NIAMS and the NIH.

NIH and NIAMS Activities

Dr. Carter reviewed the NIAMS’ budgetary situation and outlook. NIH’s strong bipartisan support in Congress led to a 5.4% increase in its budget, or approximately two billion dollars, in fiscal year (FY) 2019. A significant portion of this increase was allocated to specific programs and initiatives, such as the BRAIN Initiative, the Cancer Moonshot, and efforts to address the opioid crisis. NIAMS received a 3.1% budget increase, from $586.7 million to $606.1 million.

Dr. Carter briefly noted some important NIH-wide policy issues that have been focus areas for the agency. NIH has a major program underway to address sexual harassment in the biomedical workplace. NIH leadership has released a statement on the topic that reiterates NIH’s core values of equality and a safe work environment. NIH Director Francis Collins has established a working group under the Advisory Committee to the Director to delve into this issue and draft findings and recommendations.

NIH has also begun tackling the issue of foreign influence in NIH-funded research, which can manifest itself in undisclosed financial support from foreign sources and peer review violations. Recent cases, some of which have received press coverage, might suggest that this is a growing trend.

Dr. Carter briefly touched on recent personnel changes at the NIH level. Dr. Noni H. Byrnes has been named the new Director of the Center for Scientific Research (CSR) after serving several months in an acting role. Dr. Douglas R. Lowy will be serving as the Acting Director of the National Cancer Institute (NCI) after the departure of Dr. Ned Sharpless. Dr. Debara L. Tucci will be joining NIH as the new Director of the National Institute on Deafness and Other Communication Disorders (NIDCD).

At the NIAMS level:

  • Dr. Mariana Kaplan has been named a Deputy Scientific Director in the Intramural Research Program.
  • Dr. Stephanie George is the new Program Officer for the Molecular Transducers of Physical Activity Consortium (MoTrPAC). Dr. George previously worked for the NIH Office of Disease Prevention as a senior epidemiologist.
  • Mr. Herman Utama has been hired to serve as NIAMS’ Deputy Budget Officer. Mr. Utama previously worked as a budget analyst at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Dr. Carter updated the Council on the candidate searches for the positions of NIAMS Director, Director of the Division of Extramural Research, and Intramural Research Program Clinical Director. All three searches are active and progressing.

Dr. Carter updated the Council on the candidate searches for the positions of NIAMS Director, Director of the Division of Extramural Research, and Intramural Research Program Clinical Director. All three searches are active and progressing.

Dr. Carter discussed the memorial celebration of the life of Dr. Stephen Katz, former NIAMS Director, that was held on May 3. The event was a tribute to the tremendous support Dr. Katz gave to NIAMS and NIH over his years of service. At the celebration, Director Collins announced the creation of a new NIH-wide Stephen I. Katz R01 grant for early-stage investigators. In addition, NIAMS has established a Katz Scholar Program for young dermatologists.

Highlights of Selected Recent Scientific Advances

Dr. Carter noted that one of NIAMS’ strategies is to fund innovative, high-risk research. With that in mind, Dr. Carter drew the Council’s attention to a recent Nature article which concluded that small research teams are most likely to produce ideas that are “disruptive,” that is, ideas that transform science and technology. The authors found that larger teams were less innovative, but played a valuable role in developing existing opportunities and ideas. The publication also suggested that government-funded research was considerably less likely to fund disruptive research, regardless of team size. NIAMS is addressing this challenge through a series of funding opportunity announcements called the Research Innovations for Scientific Knowledge (RISK) awards which use a focused peer review process to encourage highly innovative research.

Dr. Carter briefly discussed several recent notable scientific publications:

  • Dr. Tatsuya Kobayashi, a NIAMS STAR Award recipient, and an international team of researchers have discovered the first case of a pathogenic gain-of-function miRNA mutation in three patients with a novel skeletal dysplasia. The research is described in an article in Nature Medicine titled “Gain-of-function mutation of microRNA-140 in human skeletal dysplasia.” Using a combination of whole genome sequencing of the patients and their families, mice models, and molecular studies, they showed the disease-associated miRNA-140 mutation not only knocked out the original functions of the molecule, but it led to new functions. This gain-of-new-function phenomenon is known as a neomorphic effect, and this paper is the first report of a neomorphic mutation as the basis for a human genetic skeletal disease.
  • Duke University’s Dr. Charles Gerbach and colleagues published an article in Nature Medicine titled “Long-term evaluation of AAV-CRISPR gene editing for Duchenne muscular dystrophy.” Gene editing via CRISPR-Cas9 strategies has attracted significant attention from patients, scientists, and therapy developers because of the tremendous potential of a one-time, permanent treatment for many genetic diseases. This study is the first to look at the long-term outcomes of this gene editing approach in a mouse model of Duchenne muscular dystrophy.  Building on earlier work showing that expression of the edited dystrophin protein persisted for eight weeks in mice, the investigators have now shown that the effects persist for at least a year.  They also studied the effects of giving the treatment to two-day old mice without fully developed immune systems, the findings from which provide further precedent for the potential advantages of treating very young patients to minimize their immune responses to gene editing components. While the results are relatively promising overall, the study shows that gene editing is not always as precise as many investigators thought and further development will be important for advancing the safest, most effective therapies.
  • Dr. Andrew Mammen from the NIAMS Intramural Program and colleagues recently published an article in Arthritis & Rheumatology titled “Myositis autoantigen expression correlates with muscle regeneration but not autoantibody specificity.” In this study, researchers evaluated muscle biopsies and cell cultures for myositis autoantigens to test the hypothesis that overexpression of a given myositis autoantigen initiates or propagates autoimmunity against that autoantigen. They found that regenerating muscle often expresses high levels of autoantigens, but autoantigen expression did not correlate with presence of the corresponding myositis-specific autoantibody from the patient, indicating that factors other than autoantigen expression contribute to autoantibody production in myositis patients. Future studies will need to investigate the mechanisms that contribute to production of single myositis-specific autoantibodies.
  • In an article in Nature Immunology, Dr. Marcus Clark (University of Chicago) and colleagues published an article titled “Quantifying in situ adaptive immune cell cognate interactions in humans.” This team developed and refined a machine learning application, called cell distance mapping, to study interactions that occur between T cells and dendritic cells during kidney inflammation, or nephritis, in lupus patients. This new technique allows researchers to study dynamic interactions between T cells and dendritic cells in tissue from patients for the first time. Information gained from this technology is expected to improve our understanding of the pathogenesis of lupus nephritis and potentially provide new directions for therapy development.
  • Dr. Virginia Pascual (Weill Cornell Medicine) and colleagues published an article titled “A CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate” in Nature Medicine. This research team discovered a unique subset of T cells that is expanded in the blood and kidneys of lupus patients with proliferative nephritis. Compared to other T cells that are known to play a role in lupus, these cells have different genomic features and use a unique mechanism to activate the B cells that produce autoantibodies thought to contribute to nephritis. Preliminary studies show that this new T cell subtype is associated with specific histological classes of lupus nephritis, suggesting that it might serve as a biomarker to help better distinguish between lupus patients with different types of kidney disease. The findings also present a new opportunity to develop therapies that specifically target the detrimental immune responses that lead to autoantibody production in lupus.
  • Yale University’s Dr. Valerie Horsley led a NIAMS-supported team in publishing an article in Science called “Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair.” This study characterized myofibroblast cells in the skin and provided new information about how signals from macrophages in wound beds influence them.  The researchers showed that specific macrophages selectively stimulate proliferation of one distinct subpopulation of myofibroblasts. They also identified two cytokines secreted by wound bed macrophages as the key drivers of this proliferation. This study advances our understanding of the biological mechanisms of wound healing and could eventually allow for enhanced wound healing without scarring and improve treatment for skin conditions associated with deficient, perturbed, or excessive scarring.
  • Dr. Dorothy Dunlop and Dr. Rowland Chang, Northwestern University, led a team that published an article titled “One hour a week: Moving to prevent disability in adults with lower extremity joint symptoms” in the American Journal of Preventive Medicine. The team analyzed data from the longstanding Osteoarthritis Initiative to identify optimal activity thresholds for adults with lower extremity joint symptoms to maintain disability-free status over a four-year period.  Lower-extremity joint symptoms such as knee pain and stiffness are leading causes of disability in older adults.  Physical activity prevents disability and improves health outcomes, but there is no clinical evidence to establish the minimum amount of time and intensity of physical activity needed. Using data from the OAI, the investigators showed that one hour of moderate-to-vigorous physical activity per week, which is less than 10 minutes a day, can significantly reduce the risk of mobility disability for older patients with symptoms of knee osteoarthritis. This minimum threshold and the associated wide range of health benefits may motivate inactive older adults to begin their path toward a physically active lifestyle.

Budget Overview and Update

Dr. Carter first reminded the Council of NIH’s budget history over the past several years. Following the dramatic drop in budgets across the NIH in FY 2013 due to sequestration, the NIAMS budget has consistently received a boost over the previous year. In keeping with NIH policy, NIAMS began offering a more generous payline for new investigators in FY 2007, but modified that policy last year to include only those researchers who met the more stringent Early-Stage Investigator (ESI) criteria. NIAMS’ payline for all other R01 applicants remained constant at the 13th percentile in FY 2016, 2017, and 2018, but the payline for FY 2019 has dipped to the 12th percentile despite an increase in the Institute’s funding appropriation.


Dr. Carter said this decrease could potentially be attributed to some NIH-wide trends. Across all of NIH, both the number of applications and the average cost of funded Research Project Grants (RPGs) have consistently increased since FY 2013. The number of applications is important because it translates into an increase in the number of applications that would score within a certain percentile, meaning that the available funds would have to be split in more ways. This increase in cost correlates with an increase in the percentage of applications with non-modular budgets and an increase in multi-PI applications, which are more expensive on average. A greater average cost means that the available dollars are distributed to fewer awards. However, this NIH-wide trend is not reflected in NIAMS activity; the number of application received and the average cost of awards have remained relatively constant since FY 2016. NIAMS has looked at modular versus non-modular grants, and while the number of modular grant applications is decreasing and modular applications are increasing, the average cost for the non-modular grant awards seems to be leveling off in a pattern that is similar to what we see for all competing RPGs. Non-competing commitments, however, have shown a considerable upward trend. Thus, despite the increase in the budget for grants, a greater increase in of NIAMS funds is obligated for non-competing grants, leaving fewer funds for competing grants.

NIAMS then tried to understand the increase in the noncompeting pool. In response to sequestration, NIAMS instituted a policy reducing direct costs of competing and non-competing RPGs. Reductions from direct costs recommended for competing RPGs have been approximately 12 percent since FY 2014. Noncompeting continuation awards have been funded at the recommended level that is reflected on the prior year’s Notice of Grant Award since FY 2015. Thus, one explanation for the increase in the cost for the noncompeting grant pool is that the grants awarded with deeper cuts during the lean years are now expiring and being replaced by those with less of a cut. In essence, the $15 million increase in NIAMS’s extramural program budget was offset by a $19 million increase in noncompeting commitments.

Looking at non-competing commitments, NIAMS is typically not called upon to fully pay all them for various reasons, leaving discretionary funds available at the end of the FY that can be used to fund additional awards.  NIAMS has decided to use these funds to increase the payline from 10 to 12 percent for RPG awards. Dr. Carter emphasized that NIAMS is using these trends to develop a budget forecast to prevent similar difficulties from occurring to the extent possible.  


The Council discussed the impact of ESI funding on NIAMS’ budget outlook. Dr. Carter acknowledged that significantly more funding was devoted to ESIs that in the past, which was intentional, but that it might have had a bigger impact on the budget than anticipated. Dr. Oro said it would be important to include the ESI grant situation in relation to the R01 payline in future updates. If the budgetary complications are primarily due to NIAMS achieving one of its major goals, i.e., funding young researchers, it is something the Council will likely be willing to accept. Council members noted that the modular base has not increased in many years, a situation that will likely have to be addressed in coming years. Dr. Tapscott suggested including the number of individuals supported in future data, which would be more informative than



Dr. Carter introduced Dr. John O’Shea, NIAMS Scientific Director, to update the Council on the NIAMS IRP.

Dr. O’Shea began by providing a general overview of the program. Overall, the IRP employs approximately 275 people, including scientists, physicians, PAs, NPs, nurses, postdocs, grad students, postbacs, summer students, and administrators. The IRP represents approximately 11% of NIAMS’ budget. It includes 27 faculty members: nine Senior Investigators, seven Investigators, two Assistant Clinical Investigators, three Scholars, five Staff Clinicians, and one contract orthopaedic surgeon. Dr. O’Shea briefly discussed each of these faculty members and their areas of specialty and research topics. He specifically noted five new recruits who will be joining NIAMS this year: Catriona Harkins (Katz Scholar), Marcela Ferrada (Shulman Scholar), Pravitt Gourh (Assistant Clinical Investigator), Luis Franco (Staff Clinician), and Naoko Mizuno (Tenure Track Investigator).

Dr. O’Shea highlighted the work of several NIAMS investigators. Dr. Rafael Casellas’ lab is focused on transcriptional regulation and mammalian mediator structure. Dr. Maria Morasso’s work explores the role of SOX2 in rapid wounding. Research in Dr. Chris Nagao’s laboratory recently led to the publication of an article titled “Innate lymphoid cells control sebaceous gland homeostasis and skin microbiome” in Cell. This research found that innate lymphoid cells limit sebocyte growth via TNF and lymphotoxin and that sebaceous glands produce anti-microbial lipids and regulate the microbial landscape. Dr. Heidi Kong has been working on rare diseases, such as DOCK8 deficiency, which led to discoveries related to the skin virome in immunodeficiency. Dr. Mariana Kaplan’s lab’s recent work focuses on neutrophils and autoimmunity. Dr. Kaplan has also partnered with Dr. Peter Grayson on research related to adenosine-mediated inflammation in monogenic vasculitis and Dr. Sarfaraz Hasni on a JAK inhibitor trial for lupus. Dr. Kaplan’s research found that JAK inhibitors modulate pathogenic neutrophil pathways and reduce interferon signature and improve vascular function in lupus.

Dr. O’Shea listed a number of NIAMS employees who won awards for their work recently. Drs. Mariana Kaplan, Robert Walker, Bob Colbert, and Chris Nagao all received NIH Director’s Awards; Dr. Isaac Brownell was awarded the HHS Hubert H. Humphrey Award; and Dr. Natasha Hill was accepted into the NIH Independent Research Scholars Program. Dr. O’Shea also briefly discussed new equipment and technology that has been purchased by NIAMS.


Mr. Bill Mulvihill, NIAMS Council member and Chair of the Council’s strategic plan working group, presented the group’s report and recommendations. The charge of the working group was to consider the initial draft of the NIAMS Strategic Plan for Fiscal Years 2020-2024 at a high level and determine if there are substantial issues that are either omitted or discussed inappropriately.

First, Mr. Mulvihill felt it was crucial to bear in mind the mission of NIH and the mission of NIAMS when considering a strategic plan. NIH’s mission is “to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” NIAMS’ mission is “to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; training of basic and clinical scientists to carry out this research; and dissemination of information on research progress in these diseases.” If any proposed content for the strategic plan does not fall into these rubrics, it should not be considered.

Mr. Mulvihill invited Ms. Cindy Caughman, Branch Chief, Scientific Planning, Policy, and Analysis Branch, to present an overview of the proposed strategic plan. The strategic plan is divided into four parts: Overview and Introduction; Cross-Cutting Scientific Themes; Disease- and Tissue-Specific Goals; and Management, Scientific Stewardship, and Accountability. The cross-cutting themes and disease-specific goals sections were developed in response to the Request for Information issued by the Institute in preparation for the drafting of the strategic plan and related public meetings and listening sessions.

Overall, the working group found the strategic plan to be comprehensive and thorough across each section. The working group did note a fair amount of redundancy throughout the plan, but felt this was acceptable given how individuals are likely to interact with the plan (i.e., focusing on portions relevant to their interests). The working group also noted that the “Director’s Message” might be a place to note the rationale for these redundancies.

In working group discussion, some members thought NIAMS should consider whether disease- and tissue-specific section titles fully capture the Institute’s mission. The working group felt the plan layout and length enables researchers to determine how their work and research interests fit within the NIAMS mission. In addition, the plan provides an opportunity to employ terminology that is more specific, accurate, and clinically relevant. The working group felt that NIAMS should determine steps to measure success and hold itself accountable to the plan’s goals. One suggestion would be to create a Strategic Plan Review Committee with key staff and council members, which could track progress toward goals and report to various constituents.

The working group’s report included a number of further recommendations, broken down by strategic plan section. The overarching recommendations were to:

  • Where practical, highlight NIAMS-supported advances as a foundation for moving towards the Institute’s goal of “turning discovery into health.”
  • Focus on leveraging partnerships to advance progress throughout all mission areas.
  • Consider how the significant attention to systems and integrated approaches may be interpreted by individual investigators. This could be perceived as a deviation from NIAMS’ focus on investigator-initiated research.

Mr. Mulvihill briefly reviewed the plan section-specific recommendations and opened the floor for discussion to the full Council. The Advisory Council concurred with the report.


Dr. James noted that the strategic plan was very detailed and comprehensive. It is also very lengthy, which suggests that readers are likely to peruse the document or go directly to the sections that directly impact them. She raised the possibility of moving the cross-cutting themes section, or portions of it, to an appendix. Dr. James also suggested briefly addressing evaluation science and health equity in the plan.

Dr. Oro suggested streamlining the executive summary as much as possible to make it more digestible to the general public. Dr. Oro also felt the plan could be clearer about its stance on team science versus individual R01s. Dr. Carter said individual investigator-driven science will remain the backbone of NIAMS funded research, but team science is a valuable complementary aspect to support. In particular, team-based science is crucial for larger data sets. Find the right balance will be a challenge going forward. Dr. Lerner also noted the role of industry when it comes to team science.

The Council discussed the importance of patient-centered research, how to best include patients in the decision-making process where possible, and how to make NIAMS’ work transparent and disseminate it to patients. Dr. Ibrahim also highlighted the gap between discovery and therapeutic application, which he believes the strategic plan confronts and addresses in an admirable way.

Ms. Caughman briefly reviewed the next steps of the Strategic Plan process. A second Request for Information (RFI) will be issued to solicit feedback from stakeholders on the current draft. Following the RFI, a revised plan will be drafted incorporating feedback from stakeholders and the Council. The final draft will be presented to the Advisory Council at its September meeting, after which it will obtain final clearance and be officially released.


Dr. Carter introduced Dr. Helene Langevin, Director of the National Center for Complementary and Integrative Health (NCCIH), to deliver the presentation.

Integrative health is generally understood to be the integration of complementary treatments with conventional medicine. Another important aspect, however, is exploring how to integrate care across the whole person. A number of practices that NCCIH classifies as mind and body practices have evolved to address this angle of human health, such as meditation, mindfulness, acupuncture, and yoga, among others. Some of these therapies aim for mental effects rather than physical, but recent studies have shown that some of these techniques can have physical implications as well, for example, in pain modulation. Indeed, according to the National Health Interview Survey, pain in general, and back pain specifically, is far and away the most common reason respondents seek out complementary health treatments and mind and body practices. Joint pain and other musculoskeletal pain were also high on the list, which clearly suggests the field of complementary and integrative health is of great interest to NIAMS.

Dr. Langevin traced the historical trends in musculoskeletal and chronic pain research. In the past, the field has focused primarily on the pathology of musculoskeletal tissue, joints, the spine, vertebral discs, etc. The last couple decades have seen a shift in emphasis towards neurological chronic pain components, such as research on descending inhibition of pain and functional and structural alterations in brain networks. As a result of this research, when pain after an injury lasts more than three months, patients are now told that the tissues have healed and the brain is responsible for the ongoing pain.  Dr. Langevin believes it is worth delving deeper into what being “healed” means in this sense, and what “tissues” are being referred to. When talking about musculoskeletal tissue, one generally is referring to specialized connective tissues, such as tendons, ligaments, and joint capsules. But there are other non-specialized connective tissues that are studied much less, such as the dense fascia or interfascial connective tissue planes. These connective tissues form an interconnected network that spans the entire body across many anatomical levels (e.g., fascia, interstitium, and extracellular matrix), creating a scaffold that determines the shape of the human body. It is also known that connective tissue continuously remodels across the human lifespan in response to mechanical forces in response to gravity, externally applied forces, habitual movement patterns, and muscle contractions.  Injuries to connective tissues often go undiagnosed because there are no effective imaging techniques to identify this kind of damage. Dr. Langevin discussed research on chronic inflammation and the impact on connective tissue in mouse studies. Over time, connective tissue stiffening, lack of mobility, and muscle imbalances can lead to abnormal load distribution in the body, which in turn can put at risk vulnerable structures, such as cartilage, joints, and intervertebral discs.

Mind-based complementary health practices can assist in enhancing descending pain inhibitory pathways and research has suggested they might have beneficial effects on emotional pain processing. In addition, mind-based practices can reduce fear of movement and help correct habitual movement patterns. Improved movement changes the mechanical forces on connective tissues and can reduce movement restriction. This process is gradual, however, and if attempted too quickly can cause increased damage.

If behavioral therapies are unsuccessful or not feasible, manual physiotherapy can be attempted. Dr. Langevin discussed the results of a studies looking at the effect of manual therapy in repetitive motion rat models and the effect on neural inflammation and perineural fibrosis, and the beneficial effect of stretching on chronic inflammation. She presented other research on pro-inflammatory mediators and pro-resolving mediators that are promoted by stretching.

In conclusion, there are important interactions between the forces produced by the musculoskeletal system and the immune responses that occur in the same connective tissues that transmit those mechanical forces. A simple change in movement patterns over time can have profound effects by altering the efferent output to muscle, changing the mechanical forces that remodel the connective tissue, and reducing inflammation. This pathway crosses a number of disciplines that are currently too siloed: neuroscience, physical therapy and rehabilitation, rheumatology, and orthopaedics. More interdisciplinary collaborations are needed to further explore the mechanistic underpinning of connective tissues, the relation to chronic pain, and how physical therapy works. NCCIH is uniquely positioned to assist in this process. Dr. Langevin listed three potential areas for further development of common interests: mind and body approaches to the treatment and prevention of chronic musculoskeletal pain, mechanisms of reversible connective tissue and muscle contribution to reduced mobility and impaired function following injuries, and structural and dynamic imaging of soft tissues.


Dr. Carter said the NIH Back Pain Consortium (BACPAC) would be a good venue to explore the cross-discipline partnerships. Dr. Gayle Lester asked whether fascia can be visualized by high field MRI. Dr. Langevin said it is possible but it requires the proper sequence optimization and fat suppressed images. Even then, the layers are not well differentiated. NCCIH is hoping to work with the National Institute of Biomedical Imaging and Bioengineering (NIBIB) on this topic in the near future. Dr. Oro recommended considering the role of the gut and skin microbiome in the whole body perspective. Dr. Chen emphasized the importance of potential imaging techniques for exploring the morphology of the connective tissue. She also suggested using molecular probes to examine the cellular details of the changes in tissue.  


Dr. Lester updated the Council on NIAMS’ clinical trial landscape in preparation for the Institute’s reissuance of its clinical trials Funding Opportunity Announcements (FOAs). Dr. Lester began by presenting a slide showing the percentage of the 64 active trials by disease area. Rheumatic diseases are represented in 37% of active trials and orthopaedics in 17%. She noted skin diseases are relatively low, at 8%, but that number is growing. Dr. Lester next showed slides with data on R34 planning grants by NIAMS program area and types of trials and other grants.

Of the 64 active trials, 19 are focused on rare diseases. The patient population of the trials is primarily adult only (72%), but 11% are pediatrics only and 17% with both populations. The trials are mostly behavioral interventions and drug interventions and are distributed across all phases. Twenty-three percent of the trials involve Investigational New Drugs (INDs) and require FDA (U.S. Food and Drug Administration) approval. 

Dr. Carter next gave the Council a brief overview of the budget impact of NIAMS’ clinical trials. Over the past few years, NIAMS has spent between 6-10% of its total budget on clinical trials. He also reviewed the specific clinical trial FOAs that comprise NIAMS’ clinical trial portfolio and data on applications and success rates by type of grant.


The Council discussed the clinical trial monitoring and the financial and regulatory burden involved in this process. Dr. Carter indicated his opinion that the money spent on Data and Safety Monitoring Board (DSMB) activities is money well spent, but he acknowledged the regulatory burden can seem onerous at times to investigators.  

Ms. Castro-Lewis asked what NIAMS is doing to improve Hispanic participation in clinical trials, which has historically been well below the percentage of the population at large. Dr. Carter said that is a focus area for NIAMS and gave an example in which a certain trial was not allowed to proceed until it achieved adequate population equity.

The Council discussed with Dr. Carter the NIH’s centralized IRB plan and NIAMS’ experiences with it thus far. Dr. Carter expressed his hope that it will eventually be a more efficient and time-saving process but acknowledged that it is currently a work in progress.


Dr. Lester presented the FY 2021 NIAMS extramural funding initiatives to the Council for their consideration.

New Funding Opportunity Announcement:

  • Translation of Biomedical and Behavioral Research Results from Academic/Non-profit Lab to Marketplace (R43/R44) (Lead: Drs. Xibin Wang, Ricardo Cibotti, Fei Wang). This initiative will solicit Small Business Innovation Research grant applications from small business concerns that propose research and development studies to facilitate translation of lab discoveries from academic or non-profit institutions to marketplace to advance the diagnosis, treatment, and prevention of musculoskeletal, rheumatic or skin diseases.

New Activities: 

  • Accelerating Discovery in NIAMS Studies with Computational Models, Tools, and Workflows (Lead: Drs. Anthony Kirilusha, Ted Zheng, and Ricardo Cibotti). This initiative will explore opportunities to accelerate research in rheumatic, musculoskeletal, and skin diseases through the development, validation, and adoption of computational models, tools, and workflows. A variety of mechanisms will be used to seek community input, integrate responses with feedback from the strategic plan listening sessions, and to inform next steps.
  • Roundtable on Neurogenic Inflammation Research: Gaps and Opportunities (Lead: Drs. Ricardo Cibotti, Faye Chen, Ted Zheng, Heiyoung Park, Marie Mancini). Experimental evidence indicates that the functions of the immune and peripheral nervous systems are connected, yet the cellular and molecular mechanisms by which these systems communicate, are not fully elucidated. It is critical to fully understand the mechanisms by which sensory and autonomic signals regulate different types of immune cells at baseline and during inflammation and autoimmunity. As a result, NIAMS proposes to conduct a roundtable to identify important scientific opportunities, barriers, knowledge gaps and research needs in neurogenic inflammation research as related to NIAMS mission relevant research.
  • Advancing Research on Drug Therapies for Fracture Prevention (Lead: Drs. Faye Chen and Kristy Nicks). This initiative is a placeholder for implementing recommendations from the NIH Pathways to Prevention workshop on Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention. NIAMS intends to implement these activities in collaboration with other NIH Institutes, Centers, and Offices and federal agencies.
  • NIAMS Clinical Trial Roundtable: Who to Treat When with What (Lead: Drs. Robert Carter, Tom Cheever, Chuck Washabaugh, and James Witter). The goal of this proposed roundtable is to gather information from the NIAMS research communities to inform the NIAMS on the best trial designs to conduct research that informs clinical care. The discussions from this meeting will focus on understanding the fit between different trial designs, the intervention, and outcomes and how the evidence generated from trials influence various stakeholders in their decision-making.

Re-Issued Funding Opportunity Announcements: 

  • Resource-based Centers for Rheumatic Diseases Research and Resource-based Centers for Musculoskeletal Biology and Medicine (Lead: Drs. Marie Mancini and Faye Chen). Centers supported under these funding opportunity announcements will focus on developing and providing access to research resources.
  • Centers of Research Translation (CORT) (Lead: Drs. Yan Wang and Chuck Washabaugh). The goal of this continuation of the CORT Program is to foster translational research, directed at elucidating the relevance of basic research to human disease in an area within the NIAMS mission. A CORT must have a minimum of three highly meritorious research components consisting of one or more translational Research Projects and one or more Research Cores. Using an investigative team science approach, the projects and cores will enable the generation of new knowledge that will improve our understanding of human pathophysiology, and lead to identification of new targets, other tangible products or deliverables and development of more effective treatment, diagnostic or prevention strategies for human disease.
  • NIAMS Clinical Trial Implementation Cooperative Agreement (Lead: Dr. Tom Cheever). Awards funded under this initiative would support implementation of investigator-initiated clinical trials where applicants would be required to have completed necessary planning activities. NIAMS expects supported trials will address highly significant clinical questions with the potential for impact, and be hypothesis driven, milestone defined, and within the research mission of the NIAMS.
  • Exploratory Clinical Trial Grants in Arthritis and Musculoskeletal and Skin Diseases (Lead: Dr. Ricardo Cibotti). The purpose of the Exploratory Clinical Trials Grants Program is to foster clinical trials that can be completed within a limited timeframe and budget, and that will lead to clinically meaningful improvements in prevention, diagnosis, or treatment of NIAMS core mission diseases. Awards funded under this initiative support and facilitate clinical trials that can be completed within a limited timeframe and budget.
  • Clinical Observational Studies (COS) in Musculoskeletal, Rheumatic, and Skin Diseases (Lead: Drs. Ricardo Cibotti, Heiyoung Park, and Ted Zheng). Awards funded under this initiative would support clinical observational studies to obtain information that is necessary for designing clinical trials for musculoskeletal, rheumatic, or skin diseases or conditions. Applicants will be required to justify the need for the observational study in preparing for a future trial or trials. Applications may include characterization of cohorts similar to potential future trial participants and collection of data to justify the use of a biomarker or a patient outcome measure in a future trial. Applications for early stage development of new biomarkers or outcome measures, studies of disease mechanisms or pathophysiology, and therapeutic target identification will not be responsive to this initiative unless the resulting data is necessary for designing a clinical trial in the near term. This initiative will only support observational studies and will not support intervention studies. 


Dr. Buyon asked if NIAMS had ever given thought to partnering with other Institutes on clinical trials. Dr. Lester said she knew of a previous collaboration with the National Institute on Aging on a bone study. Dr. Carter acknowledged that these partnerships are rare and often difficult to organize, but he expressed hope that the BACPAC program will increase opportunities to work with other Institutes.


This portion of the meeting occurred during closed session.


This portion of the meeting occurred during closed session.


In closed session, the Council reviewed and recommended a total of 687 primary and 214 secondary applications. The total cost requested in year -01 for all applications was $356,185,779.



The 98th National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:00 p.m. Proceedings of the public portion of this meeting are recorded in this summary.


I hereby certify that, to the best of my knowledge, the foregoing summary and attachments are accurate and complete.

Melinda Nelson
Executive Secretary, National Arthritis and
Musculoskeletal and Skin Diseases Advisory Council
Acting Director, Division of Extramural Research
Activities, National Institute of Arthritis and
Musculoskeletal and Skin Diseases

Robert H. Carter, M.D
Acting Chairman, National Arthritis
and Musculoskeletal and Skin Diseases
Advisory Council
Acting Director,
National Institute of Arthritis and
Musculoskeletal and Skin Diseases

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