June 12, 2018


June 12th, 2018
9:00 a.m. to 3:00 p.m.

June 12, 2018 Council Webcast


The 95th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on June 12, 2018, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 10.  The meeting was chaired by Dr. Stephen I. Katz, Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). 


Council members present:

Dr. Joan E. Bechtold, Professor, Orthopaedic Surgery, University of Minnesota
Dr. Jill P. Buyon,* Director, Division of Rheumatology, Department of Medicine, New York University School of Medicine and Director, NYU Lupus Center
Ms. Magdalena Castro-Lewis, former Vice President for Programs, National Alliance for Hispanic Health
Mr. Vincent Del Gaizo,* Patient advocate and founding member and past Chair, Friends of the Childhood Arthritis and Rheumatology Research Alliance
Dr. Michael Econs, Glenn W. Irwin, Jr., Professor of Endocrinology and Metabolism; Director, Division of Endocrinology and Metabolism; Professor of Medicine and Medical and Molecular Genetics;
Indiana University School of Medicine
Dr. James Elbaor,* Director, American Institute of Orthopaedics and Sports Medicine
Dr. Michael V. Holers, Professor, Department of Medicine, University of Colorado Denver School of Medicine
Dr. Sundeep Khosla, Dr. Francis Chucker and Nathan Landow Research Professor; Director, Mayo Clinic CTSA/Center for Clinical and Translational Science; Dean for Clinical and Translational Science, Mayo Clinic College of Medicine
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,* Professor of Dermatology and Associate Director, Center for Definitive and Curative Medicine, Stanford University
Mr. Richard F. Seiden, Foley & Lardner LLP
Dr. Stephen J. Tapscott, Professor, Fred Hutchinson Cancer Research Center
Dr. Michael J. Yaszemski, Professor, Orthopaedic Surgery and Biomedical Engineering, Mayo Clinic

*Ad hoc for this meeting.

Staff and Guests

The following NIAMS staff and guests attended:


Ms. Gema Souto Adeva
Dr. D. Lee Alekel
Mr. Steve Austin
Ms. Pamela Beheler
Ms. Elizabeth Bouras
Dr. Amanda Boyce
Mr. Gahan Breithaupt
Dr. Nakia Brown
Dr. Stephanie Burrows
Ms. Justine Buschman
Dr. Robert Carter
Ms. Cindy Caughman
Dr. Faye Chen
Dr. Thomas Cheever
Ms. Jennifer Chi
Dr. Ricardo Cibotti
Dr. Jonelle Drugan
Ms. Colleen Dundas
Ms. Elizabeth Elliott
Ms. Barbara Footer
Dr. Nancy Garrick
Ms. Aleisha James
Ms. Katie Joffee
Mr. Andrew Jones
Dr. Stephen I. Katz
Ms. Shahnaz Khan
Mr. Mark Langer
Mr. Greg Lavine
Dr. Gayle Lester

Dr. Helen Lin
Ms. Leslie Littlejohn
Dr. Yin Liu
Dr. Kan Ma
Dr. Marie Mancini
Dr. Su-Yau Mao
Dr. Kathryn Marron
Ms. Leslie McIntire
Ms. Melinda Nelson
Dr. Van Nguyen
Dr. Kristy Nicks
Dr. Heiyoung Park
Ms. Amita Patel
Mr. Rick Phillips
Ms. Andree Reuss
Mr. Neil Roberts
Dr. Kathy Salaita
Dr. Vittorio Sartorelli
Dr. Susana Serrate-Sztein
Ms. Robyn Strachan
Ms. Jamie Thompson
Ms. Susan Toy
Dr. Hung Tseng
Dr. Fei Wang
Dr. Yan Wang
Dr. Chuck Washabaugh
Ms. Robin Wolz
Dr. Xincheng Zheng


Dr. Diana Bianchi, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH
Dr. Rachel Caspi, National Eye Institute, NIH
Mr. Douglas Fesler, American Society for Bone and Mineral Research
Dr. Anthony Kirilusha, National Human Genome Research Institute, NIH
Ms. Linda Markham, Dermatology Nurses’ Association
Mr. Blake McDonald, American Academy of Dermatology
Ms. Jessica Nagro, National Psoriasis Foundation
Mr. Vincent Pacileo, Arthritis Foundation
Dr. Amy Patterson, National Heart, Lung, and Blood Institute, NIH


A motion was made, seconded, and passed to approve the minutes of the 94th NAMSAC meeting, held on February 7, 2018.


Future Council meetings are currently planned for the following dates:

September 5, 2018
February 5, 2019
June 12, 2019
September 10, 2019
February 4, 2020
June 9, 2020
September 1, 2020


Dr. Katz reminded Council members that the open session of this NAMSAC meeting was being videocast and will be archived on the NIH website.  The February Council meeting has logged more than 260 views, either in real time or after the meeting.  Dr. Katz invited Council members to encourage their colleagues to view the proceedings of this meeting online at the NIH Center for Information Technology’s VideoCasting and Podcasting website.  


Dr. Katz welcomed and introduced the following individuals serving as ad hoc Council members for this meeting:


  • Dr. Jill P. Buyon, Director of the Division of Rheumatology in the Department of Medicine at New York University (NYU) School of Medicine and the Director of the NYU Lupus Center.  Dr. Buyon’s laboratory work centers on defining the mechanisms by which autoantibodies result in congenital heart block in the developing fetus and organ injury in adults with systemic lupus erythematosus.
  • Mr. Vincent Del Gaizo, father of a patient with systemic onset juvenile idiopathic arthritis.  For the past 16 years, he has been involved in pediatric rheumatology research, directly contributing the patient voice and perspective to research initiatives.  He is a founding member and past Chair of the Friends of the Childhood Arthritis and Rheumatology Research Alliance, a nonprofit organization established to promote research on pediatric rheumatic conditions.
  • Dr. James Elbaor, Director of the American Institute of Orthopaedics and Sports Medicine in Dallas/Ft. Worth, TX.  Dr. Elbaor is a clinician specializing in surgical and nonoperative treatments for patients suffering from spinal issues and a longstanding member of the North American Spine Society.
  • Dr. Anthony Oro, Professor of Dermatology and the Associate Director of the Center for Definitive and Curative Medicine at Stanford University.  Dr. Oro’s research interests encompass cancer genomics and tumor evolution, stem cell biology, and hair and skin development and regeneration, while his clinical interests include non-melanoma skin cancer and therapies for genetic skin diseases.


Dr. Katz thanked Dr. Bechtold for leading the Council Agenda Working Group, noting that this NAMSAC meeting’s agenda was influenced by direct input from that group. 

  • Dr. Diana Bianchi, Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) discussed pediatric research and opportunities for enhanced partnerships between the NIAMS and NICHD.
  • Dr. Amy Patterson, Chief Science Advisor at the National Heart, Lung, and Blood Institute (NHLBI), provided an update on regenerative medicine activities that NIH is developing to implement provisions of the 21st Century Cures Act.

Budget and Congressional Activities

Dr. Katz reported that the NIH is grateful for Congress’ bipartisan, bicameral support that resulted in a considerable budget increase for the NIH (and the NIAMS) for the remainder of fiscal year (FY) 2018.  Some of the NIH increase is going to address the growing prevalence of Alzheimer’s disease, and some will address the epidemic of opioid addiction and overdose.  The NIH will be doubling its research funding for pain and addiction, including the newly introduced Helping to End Addiction Long-term (HEAL) initiative.  Dr. Katz noted that opioids are prescribed for many of the conditions covered by the NIAMS portfolio; it is hoped that the Institute’s investigator communities and the patients being served will benefit from this additional research support.

The NIAMS has published its payline for investigator-initiated R01 applications and other funding mechanisms online for years.  The Institute’s FY 2018 funding plan is available here.  As was the case last year, the NIAMS payline this year is at the 13th percentile.  The payline for early stage investigators (ESIs) is at the 22nd percentile this year.  Dr. Katz explained that the Institute reserves a small portion of each year’s budget for projects that address subjects of particular relevance to its scientific and health priorities, even if their assigned scores and percentile rankings would not qualify for funding under the current payline.  There is no application process for this type of select pay funding.  Suggestions come from NIAMS staff, and Council input is welcomed in this area.  This select pay process is described on the NIAMS website, as are graphs depicting the number of R01 applications that NIAMS received and funded as a function of the scores these applications received during the peer review process.  Dr. Katz presented a graph showing the number of R01 applications and awards for experienced and new and early stage investigators in 2017.  The NIAMS website also includes separate figures depicting the funding distribution for applications and awards from each category (experienced and new and early stage investigators).

On April 11, 2018, the House Labor, Health and Human Services (HHS), and Education Appropriations Subcommittee held a hearing on the NIH FY 2019 Budget.  Members from the House of Representatives asked NIH Director Dr. Francis Collins about several topics related to NIAMS, including the Accelerating Medicines Partnership (AMP), lupus, chronic pain, and the importance of investigator-initiated research.  Senate Appropriations Subcommittee members asked about opioids, big data, clustered regularly interspaced short palindromic repeats associated genes (CRISPR-Cas) in the context of muscular dystrophy, and other topics when Dr. Collins testified on May 17, 2018.

Since the last NAMSAC meeting, NIAMS Deputy Director Dr. Robert Carter participated in a series of Congressional courtesy visits organized by the American Academy of Dermatology Association (AADA).  AADA President Dr. Suzanne Olbricht, staff members, and Dr. Carter spent a full day on Capitol Hill, meeting with Senator Susan Collins (R-ME); Representatives Rosa DeLauro (D-CT), John Moolenaar (R-MI), and Martha Roby (R-AL); and staff to Senator Joe Manchin (D-WV), Senator Patty Murray (D-WA), and Representative Chellie Pingree (D-ME).  Members and their staff were interested in a range of dermatological conditions that affect their constituents.

On April 4, 2018, the NIAMS Coalition hosted its biennial tour day for Congressional offices.  Staffers visited the NIH Clinical Center to learn more about the NIH and the NIAMS, and toured clinics and labs within the NIAMS Intramural Research Program.  On behalf of the Institute, Dr. Katz expressed appreciation for the efforts of Coalition Co-Chairs Stephanie Hazlett (of the American Academy of Orthopaedic Surgeons) and Anna Hyde (of the Arthritis Foundation), as well as the other members of the Coalition Steering Committee, for organizing this event.  The Coalition includes roughly 90 voluntary and professional organizations.

NIH and NIAMS Activities, Including Personnel Changes and Organization

Dr. Katz explained that large projects like All of Us, which generate a considerable amount of data that must be findable, accessible, interoperable, and reusable to provide taxpayers with the expected return on their investment.  He reminded Council members that during the February NAMSAC meeting, National Institute of General Medical Sciences Director Dr. Jon Lorsch provided an update on the NIH Strategic Plan for Data Science, which articulates the overarching goals, strategic objectives, and implementation tactics for modernizing the NIH-funded biomedical data science ecosystem.  Since then, the final plan has been published on the NIH website (available here).  The NIH is starting to implement the plan under the guidance of the NIH Scientific Data Council (co-chaired by Drs. Katz and Lorsch) while the NIH conducts a search for a Chief Data Strategist to lead this NIH effort.

The NIAMS, National Institute on Aging, and the NIH Office of Disease Prevention are planning a Pathways to Prevention workshop on the Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention.  The idea for this workshop originated from previous Council discussions and will be held on October 30-31, 2018, in the Natcher Conference Center on the NIH Campus.  Dr. Faye Chen, Program Director in the NIAMS Rare Diseases and Integrated Physiology of Bone Program, is leading this effort on behalf of the Institute.

Dr. Katz reported that since the last NAMSAC meeting, the AMP for Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) released its phase 1 datasets characterizing individual cells in RA and SLE disease tissue.  Scientists from across the biomedical research community are invited to access the datasets to explore important research questions about these autoimmune conditions. Additional information is available on the NIAMS AMP website.

The development, support, and retention of the next generation of investigators is a high priority at the NIH.  Dr. Katz noted that during the September NAMSAC meeting, Council members will be provided with an update on the Next Generation Researchers Initiative, which will prioritize funding for R01-equivalent applications from ESIs and investigators who are at risk of losing all NIH funding or who have only one active award.  An Advisory Committee to the NIH Director (ACD) working group presented preliminary recommendations regarding the initiative later this week (this event was videocast and subsequently made available on the NIH Center for Information Technology’s VideoCasting and Podcasting website).  Final recommendations will be issued this December, and the changes will be implemented in FY 2019.  This is reflected in the President’s FY 2019 Budget proposal, which includes a dedicated fund of $100 million in the Office of the Director to incentivize additional Institute and Center (IC) support for these scientists. 

Council discussions often focus on the importance of supporting innovative, high risk research that has the potential to make major contributions to the fields of arthritis and musculoskeletal and skin diseases research.  In 2016, NIAMS released a series of funding opportunity announcements called the Research Innovations for Scientific Knowledge (RISK) to encourage such projects.  Dr. Katz reported that those funding opportunity announcements have now closed and the awards have been made, making this an appropriate opportunity to discuss the community’s response and the program’s future.  Later during this NAMSAC meeting, NIAMS Program Officers Drs. Hung Tseng and Amanda Boyce provided additional information on RISK.

With regard to personnel changes at the NIH, Dr. Richard Nakamura retired from his position as Director of the NIH Center for Scientific Review (CSR) after 39 years of Federal service.  Dr. James Battey, who served as Director of the National Institute on Deafness and other Communication Disorders for the past 20 years, retired this month following 35 years of Federal service

HHS and NIH Activities

Within the NIAMS:


  • Dr. Richard Siegel has accepted an opportunity to serve as Global Head, Translational Medicine Discovery and Profiling for the Autoimmunity, Transplantation, and Inflammatory Disease area at Novartis Institutes for Biomedical Research in Basel, Switzerland.  Dr. Siegel will be leaving the NIH and his position as Clinical Director at the NIAMS this month, and a nationwide search will be conducted to fill the Clinical Director position.  During the search process, NIAMS Deputy Clinical Director and Chief, Pediatric Translational Research Branch Dr. Robert Colbert, has agreed to serve as the Acting NIAMS Clinical Director, effective June 15, 2018. 
  • The NIAMS Extramural Program has been reorganized.  It used to include two scientific Divisions comprised of 17 Research Programs that have now been reorganized into five topical scientific teams under a single Division of Extramural Research (DER).  The DER also manages a Special Programs Team to oversee small business awards and training programs.  Within the Division of Extramural Research, the Office of Extramural Operations (OEO) coordinates essential NIAMS activities, such as those of the Council, as well as clinical trials oversight, grants management, and the review of grant applications.  Dr. Gayle Lester is serving as DER Acting Director and NAMSAC Executive Secretary Ms. Melinda Nelson is overseeing the OEO while the Institute seeks to permanently fill these positions.  The Institute is also looking for four or five new Program Directors to help manage its portfolios.
  • Also within the NIAMS Extramural Program, Mr. Andrew Jones has been named as the new Chief Grants Management Officer after serving as the Deputy Grants Management Officer for 10 years.  Ms. Barbara Footer, a Health Science Specialist in the OEO, is retiring after 11 years of Federal service.
  • Dr. Susana Serrate-Sztein has been named as the Institute’s first Associate Director for Strategic Initiatives.  This new role entails leading and coordinating several trans-NIH initiatives and overseeing the evaluation of high-profile strategic activities.  Dr. Katz commented that Dr. Serrate-Sztein’s scientific leadership of large projects such as the Patient-Reported Outcomes Measurement Information System (PROMIS)® and the AMP RA/SLE, as well as her experience as Director of the former Division of Skin and Rheumatic Diseases, have positioned her perfectly for this role.
  • The Institute is planning to restructure its Office of Science Policy, Planning and Communications.  Dr. Nancy Garrick, Chief of the Communications and Public Liaison Branch, will remain responsible for all communications and public liaison activities, including interactions with the NIAMS Coalition.  Ms. Cindy Caughman, Chief of the Science Policy and Planning Branch, will continue to be responsible for the Institute’s planning and legislative activities.  Both Branches will be reporting to Mr. Gahan Breithaupt, NIAMS Associate Director for Management and Operations.  Ms. Anita Linde, Director of the Office of Science Policy, Planning and Communications, is on detail with the National Cancer Institute’s Office of Management.

Highlights of Selected Recent Scientific Advances

Dr. Katz described several scientific advances of interest to the Council.


  • Dr. Katz presented a slide showing a Federation of American Societies for Experimental Biology BioArt winning image from the laboratory of Dr. Charlotte Peterson at the University of Kentucky depicting the fusion of satellite cells to form myotubes with their multiple nuclei.  Dr. Peterson is on an Intergovernmental Personal Act assignment to NIAMS to help with the Molecular Transducers of Physical Activity (MoTrPAC) initiative.  The image from Dr. Peterson’s laboratory was featured in a March 29, 2018, NIH Director’s Blog post (available here).
  • Related to satellite cells—which play an important role in the growth, maintenance, and repair of skeletal muscle—Dr. Hang Yin and colleagues at the University of Georgia determined that intracellular oxygen levels regulate satellite cell behavior, identified one of the proteins involved, and demonstrated that controlling this protein’s behavior can affect muscle recovery after injury and engraftment of donor satellite cells into a new niche.  Understanding the regulation of quiescence in satellite cells may eventually lead to therapeutic manipulation of the stem cell pool in muscle diseases and disorders where repair and regeneration of muscle are inadequate.  In addition, manipulating “stemness” may make satellite cell transplantation a potential treatment option (J Clin Invest. 2018 Mar 13. pii: 96208. doi: 10.1172/JCI96208. [Epub ahead of print] PMID: 29533927).
  • Building on their previous success of generating skeletal muscle from cells taken directly from humans, Dr. Nenad Bursac and his group at Duke University reported successful production of enough stem cells to generate 3-dimensional functional human skeletal muscles.  The researchers demonstrated the ability to differentiate immature stem cells into satellite-like cells that make muscle, identified conditions that allowed these cells to form 3-dimentional muscle bundles, and showed that these muscle bundles can generate force and are responsive to electrical and chemical stimulations.  Furthermore, they implanted these muscle bundles into a mouse model, where the bundles incorporated into the host mouse tissues.  This approach has the advantage of providing an unlimited cell source.  In addition to ultimately being useful for producing muscle tissue that can replace diseased or destroyed muscle, 3-dimensional human skeletal muscle models can also be used to study diseases and to evaluate potential drugs (Nat Commun. 2018 Jan 9;9(1):126. doi: 10.1038/s41467-017-0263604. PMID: 29317646).
  • Dr. David Goldhammer at the University of Connecticut and colleagues discovered that the heterotopic ossification that characterizes the rare bone disease fibrodysplasia ossificans progressiva (FOP) originates from a type of progenitor cell called the fibro/adipogenic progenitors.  They arrived at this conclusion using a mouse model of FOP in which they showed that fibro/adipogenic progenitor cells bearing the FOP mutation are a major contributor to both injury-induced and spontaneous bone formation and cause excess bone to accumulate in essentially all major anatomical sites where lesions form in FOP patients.  In addition, the investigators showed that the protein activin A is involved in heterotopic ossification formation and that an antibody directed against activin A can suppress this process. Dr. Katz noted that is important because identifying the cells and molecules responsible for excessive bone formation may facilitate development of therapeutic approaches for FOP patients and also heterotopic ossification in wounded warriors (Nat Commun. 2018 Feb 2; 9:471. PMID: 29396429).
  • Dr. Timothy Bhattacharyya (Head, Orthopedics Research, NIAMS Clinical Trials and Outcomes Branch), is studying the rare bone disease melorheostosis, which affects the growth and development of bone and soft tissue and displays a “dripping wax” pattern that is observed in x-rays of the affected bones of patients.  Some of his group’s latest findings come from sequencing analyses on unaffected and diseased bone from 15 patients to identify a genetic cause of this extremely rare bone disease.  They uncovered an important role of the signal transduction protein MAP2K1 in bone formation and identified a somatic mutation in MAP2K1 as the genetic cause of the disease.  The research also implicates that inhibition of MEK1, a protein that operates upstream of MAP2K1, as a potential treatment strategy (Nat Commun. 2018 Apr 11;9(1):1390. doi: 10.1038/s41467-018-03720-z. PMID: 29643386).
  • Dr. Marianna Kaplan, Senior Investigator and Chief of the NIAMS Systemic Autoimmunity Branch as well as Acting Director of the Lupus Clinical Trials Unit, led a team comparing 64 lupus patients who had mild disease with healthy controls.  They found that the lupus patients had increased inflammation, stiffness, and dysfunction of blood vessels.  The patients also had increased coronary plaque burden, much of which was due to noncalcified plaque, which enhances a person’s risk of coronary heart disease.  Building on earlier work, the investigators examined low density granulocytes, a subset of neutrophils that are abundant in the blood of lupus patients, and were able to link these cells to vascular damage and cardiovascular risk in lupus patients (JCI Insight. 2018 Apr 19;3(8). pii: 99276. doi: 10.1172/jci.insight.99276. [Epub ahead of print] PMID: 29669944).
  • A collaboration between Dr. Kaplan’s laboratory and Dr. Holer’s group is examining the earliest steps in the RA disease process, which could yield strategies to preempt or prevent RA.  Previous work indicated that the molecular mechanisms responsible for RA may begin in the lungs years before the onset of clinical symptoms, with the formation of autoantibodies called antibodies to citrullinated protein antigens (ACPAs) serving as a critical early step in the process.  In this study, the researchers sought to identify the proteins targeted by ACPAs, and understand what triggers ACPAs to form.  They identified several proteins that are recognized by ACPAs and are present in the lung sputum of individuals with, or at risk for, RA.  They also found that some ACPAs were associated with very high sputum levels of structures called neutrophil extracellular traps (NETs), providing support for the hypothesis that immunogenic proteins within the NETs may cause ACPA formation.  This study has narrowed down the potential self-proteins or peptides that may trigger the production of autoantibodies in RA and provides evidence for a potential mechanism for generating those autoantibodies (Arthritis Rheumatol. 2018 April 70 (4): 516-527. DOI: 10.1002/art.40401. Epub 2018 Mar 2. PMID: 29266801).
  • Dr. Holers noted that NIAMS K23 awardee Dr. Mary Kristen Demoruelle played a critical role in this research and is also exploring other mucosal sites.
  • In RA, cells called fibroblast-like synoviocytes (FLS) secrete pro-inflammatory factors, invade and degrade cartilage, and mediate the progressive destruction of the joints.  Although anti-FLS therapies are viewed as a potentially useful approach for modifying disease course when used in combination with traditional or biologic immunomodulators, all of the currently available treatments for RA target the immune cells involved in the disease and none are specific for FLS.  A team of researchers led by Drs. Soumya Raychaudhuri and Michael Brenner at Brigham and Women’s Hospital discovered that FLS can be divided into subsets with distinct molecular functions and biological roles.  Moreover, one subset was expanded in active RA, and associated with increased immune cells and greater disease activity.  Although further studies are needed to understand precisely how changes in FLS subsets are involved in a variety of clinical aspects in RA, the knowledge provided by this and future studies could be used to develop precise therapies for RA (Nat Commun. 2018 Feb 23;9(1):789. doi: 10.1038/s41467-018-02892-y. PMID: 29476097).
  • The drug dimethyl fumarate, or DMF, is approved by the U.S. Food and Drug Administration for multiple sclerosis and is approved for psoriasis by the European Commission.  Dr. Maria Trojanowska and her colleagues at Boston University School of Medicine investigated whether DMF can modulate skin fibrosis associated with scleroderma.  They isolated skin fibroblasts from either healthy donors or scleroderma patients, treated the cells to induce expression of profibrotic genes, and found that follow-up treatment with DMF efficiently blocked the fibrosis.  Gene expression studies identified a set of pro-fibrotic genes that were suppressed by DMF.  This and other findings from the same study support the potential use of DMF as a therapeutic treatment for scleroderma-associated fibrosis (J Invest Dermatol. 2018 Jan;138(1):78-88. doi: 10.1016/j.jid.2017.08.024. PMID: 28870693). 
  • Results from the laboratory of Dr. Lloyd Miller at Johns Hopkins University School of Medicine point to IL-36 as the cytokine regulating inflammation and bacterial clearance in the context of Staphylococcus aureus epicutaneous exposure.  Using mouse and cell-culture studies, they demonstrated that epicutaneous S. aureus exposure drives IL-36R dependent skin inflammation.  This signaling by T cells mediates skin inflammation, and IL-36alpha directly induces T cell production of IL-17, which is required for inflammation (Cell Host Microbe. 2017 Nov 8;22(5):653-666.e5. PMID: 29120743).
  • Increasingly, data suggest that osteoporosis risk, fracture rates, and the cost of treatment are increasing in the Hispanic population.  These studies have focused mainly on Mexican Americans despite evidence that Hispanic subgroups have different rates of bone loss.  Now, data from the Boston Puerto Rican Osteoporosis Study suggests that Puerto Rican and non-Hispanic white women have similar rates of osteoporosis, and the middle-aged Puerto Rican men in this study are more likely to have osteoporosis than older Puerto Rican men.  This finding is important because understanding osteoporosis and low bone mass in different populations will allow for better screening, diagnosis, and treatment that can lead to decreased overall costs and improved quality of life for those at risk or with disease (J Bone Miner Res. 2018 Mar;33(3):396-403. doi: 10.1002/jbmr.3315. Epub 2017 Dec 7. PMID: 29044768).

Concluding Remarks

Dr. Katz concluded his Director’s Report by noting that recruitment for the All of Us research program—a historic effort to gather data from more than 1 million people—is underway for participants who will share their electronic medical records.  A subset of these individuals will provide blood and urine samples and will wear a device that gathers their health data in real time.  In March, Dr. Carter and Council member Dr. Judith James participated in a workshop on research priorities that will help to shape the protocol for the program.  To introduce the discussion session, Dr. Katz invited Dr. Carter to provide a brief update on the March workshop.


Dr. Carter reminded Council members that Dr. Eric Dishman, Director of the All of Us Research Program, presented an update on All of Us during a recent NAMSAC meeting.  The goals of the workshop were to develop use cases for a protocol to attract 1 million individuals and collect demographic, genomic, environmental exposure, and other data; identify research questions; establish the requirements for data collection to answer these questions; and explore ways to share the data across different questions.  The public was invited to submit questions that could be answered through All of Us; roughly 500 such questions were received in advance of the workshop.  An additional 700 use cases were generated during the workshop.  Also during the workshop, attendees examined the requirements (e.g., the types of data that could be collected) and considered potential protocol elements.  A starter protocol was developed for capturing data, storing data, obtaining samples, etc.  The next version of the protocol will be developed through an iterative process and will introduce high-priority items that address public health questions and questions that cut across many diseases.  It will emphasize genetics, recruiting under-represented populations, environmental exposure, and lifestyle.  A group of IC Directors will work with a science committee comprised of investigators and participants to prioritize the data set of uses cases and list of potential protocol elements.

In response to questions from Dr. Oro about how the medical data accumulate, what questions are asked, and whether there is still an opportunity to submit tissue-based questions, Dr. Carter explained that in terms of electronic health record data, there are two sources.  Federally Qualified Health Center data will be moved directly.  For others who are at participating large centers and foundations, a system has been put in place to extract data from electronic health records.  Dr. Carter explained the All of Us enrollment process and how certain data are collected through regular surveys that are expected to be updated to ask new questions (e.g., screening for autoimmune diseases, changes in skin, etc.).

Ms. Castro-Lewis asked about the target number for Hispanic enrollees and what strategies have been put in place to meet this goal.  Dr. Carter explained that although he did not have the target number for Hispanic enrollment available, the overall target is for more than 50% of All of Us participants to be from under-represented minority groups.  This goal will be met through the Federally Qualified Health Centers and through targeted enrollment efforts by other partners.  Dr. Katz added that minority groups will be over-represented in the initial solicitation.

Dr. Holers asked about what type of blood tests will be administered to All of Us enrollees.  Dr. Carter indicated that he did not have the exact specifics on the type of blood tests, but noted that roughly 30 samples from every enrollee who agrees to participate will be shipped to the Mayo Clinic and stored there for future testing (blood tests will be paid for through All of Us).  Dr. Carter added that there is a large patient participation component to All of Us and that patients will be provided with access to the data as it is released.  Dr. Holers also noted that there is a large opportunity to focus on autoimmune diseases that span the NIH ICs, and asked if there are opportunities for cross-disciplinary work through All of Us.  Dr. Carter explained that NIH ICs are being encouraged to explore high priority, high impact topics such as autoimmune diseases and solicit protocols in these areas.

Dr. Khosla asked about how the NIAMS will monitor the impact of the payline on early career investigators.  Dr. Katz explained that the Next Generation Research Initiative is working to ensure these early career investigators remain engaged in the research enterprise.  The Institute will be looking at the success rate of subsequent grant applications (either a renewal of the first grant or a second grant) for early career investigators as one way to determine success.

Mr. Mulvihill asked about lessons learned with regard to the collaborative aspect of the AMP.  Dr. Carter explained that these types of partnerships that bring the NIH, industry, and foundations together have been found to be extremely useful.  The NIAMS remains open to these types of partnerships, and collaborations like the AMP have changed the way research is conducted.  Mr. Mulvihill also emphasized the importance of accelerating discovery to benefit patients.  Dr. Buyon noted that from a lupus perspective, the AMP represents the first time that there has been a multi-institutional commitment in which tissues are obtained from across the country, across all ethnicities and races, in a way to normalize the way protocols are done.

Ms. Castro-Lewis asked if All of Us was engaging with community-based organizations as a way to reach out to the Hispanic community and increase Hispanic enrollment.  Dr. Carter indicated that this was the case. 


Dr. Patterson reminded Council members that the 21st Century Cures Act was passed at the end of 2016 through a bipartisan effort aimed at accelerating the development of new therapies.  Key provisions of the 21st Century Cures Act that affect HHS and NIH address: reduction of administrative burden to the NIH and researchers; privacy and data access; inclusion and workforce; ClinicalTrials.gov; programs, authorities, and trans-agency activities; and innovation projects.  The 21st Century Cures Act established the NIH Innovation Account, which specifically lends financial support (roughly $4.8 billion has been authorized over 10 years, beginning in FY 2017, outside of normal NIH appropriations) to four major projects:

  • Precision Medicine Initiative (PMI, $1.45 billion)
  • Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative ($1.5 billion)
  • Cancer Moonshot ($1.8 billion)
  • Regenerative medicine ($30 million).

The regenerative medicine provisions in the 21st Century Cures Act are applicable to the NIH, FDA, and National Institute of Standards and Technology (NIST).  Dr. Patterson commented that the regenerative medicine portion of the NIH Innovation Account is a testament to Congress’ recognition of the growing promise of this field and its associated emerging technologies.  The regenerative medicine provisions applicable to the NIH, FDA, and NIST reflect the themes of accelerating progress, scientific rigor, appropriate regulatory oversight and standards, and stimulating innovation and partnership.  The Act specifies that the NIH, in coordination with the FDA, will “award grants and contracts for clinical research to further the field of regenerative medicine using adult stem cells, including autologous stem cells…not to exceed a total of $30 million, as follows: FY 2017: $2 million, FY 2018: $10 million, FY 2019: $10 million, and FY 2020: $8 million.”

Dr. Patterson explained that the Regenerative Medicine Innovation Project (RMIP) provides an opportunity to catalyze a focused and collaborative, systematic trans-NIH approach to advancing the field.  The NIH is working with the FDA, NIST, and the research community to address patient safety, public trust, and the integrity of clinical research in regenerative medicine.  This approach will be consultative and inclusive, stimulate new partnerships, and focus on critical issues and challenges in the field.  This enterprise-level project represents a collaboration among 12 ICs and will be a coordinated, systematic, and comprehensive approach in determining the path forward.  Governance and oversight will feature an NIH Subject Matter Expert Working Group, a Senior Oversight Committee established by the NIH Director (of which Dr. Katz is a member), ACD consultation and review, the NIH Director as the ultimate decision maker, and regular reports to Congress on progress.

In terms of engagement with FDA, NIH has been working to prepare an RMIP workplan as requested by Congress, developing Funding Opportunity Announcements (FOAs) for FY 2017 and FY 2018, determining whether applicants will need Investigational New Drugs/Investigational Device Exemptions (IND/IDEs), developing plans for FY 2018 and beyond, and workshop planning on RM innovation with a focus on adult stem cells.

Dr. Patterson noted that the Act has a matching requirement.  The awards made are contingent on the awardee bringing at least one non-Federal dollar to the table for every Federal dollar in the award.  This effectively takes the $30 million budget for regenerative medicine in the NIH Innovation Account and amplifies it to at least $60 million.  She described the clinical features of eight funded FY 2017 RMIP applications (funded as competitive supplements or revisions to existing projects), including one on wound healing and epidermolysis bullosa therapy using induced pluripotent stem cell (iPSC) targeting.

To confer with the research community regarding key challenges and barriers associated with moving some of the discoveries into late-stage translational and clinical work in FY 2018 and beyond, the NIH and FDA co-hosted the Regenerative Medicine Innovation Workshop on December 6-7, 2017.  Both Dr. Collins and FDA Commissioner Dr. Scott Gottlieb provided remarks during the event, which focused on six areas of particular clinical promise (including musculoskeletal tissues and integument) as well as two regulatory science sessions and a multidisciplinary discussion of critical gaps and solutions.  Despite the disparate clinical fields represented at the workshop, the critical challenges and “pain points” strongly resonated across disciplines.  These included:

  • The intrinsic nature of cell-based products presents challenges to achieving current good manufacturing practice (cGMP) compliance
  • Difficulties in obtaining assistance with preparation of cGMP-compliant stem cell products
  • A call for regulatory “coaching” support to enable submission of well-supported IND/IDE applications
  • Limited understanding of the identity and nature of stem cell products used in the clinic.

A proposed approach for advancing the regenerative medicine field from FY 2018 and beyond was developed.  This approach includes funding rigorous regenerative medicine clinical research with optimal stewardship through: (1) soliciting investigator-initiated proposals that address widely recognized regenerative medicine challenges, (2) a strategic focus on clinical trials and late-stage IND/IDE-enabling pre-clinical studies, (3) implementing a phased, performance milestone-driven approach to funding regenerative medicine clinical trials, and (4) promoting data sharing.  The proposed approach also proactively addresses critical challenges by identifying core resources, technology platforms, and infrastructure that could be leveraged to catalyze innovation; and forging key partnerships and collaborations.

Dr. Patterson concluded her remarks by inviting Council members to visit www.nih.gov/rmi for more information and explaining that the provisions in the 21st Century Cures Act for the RMIP serve as a timely stimulus for NIH and FDA to work together to galvanize the field; foster major scientific advances; address key regulatory and technical issues in product development and clinical investigation; and ensure that regenerative medicine clinical studies are standardized, reproducible, and generalizable.  Feedback on the RMIP can be submitted to RMIP@nih.gov.


Dr. Katz asked Dr. Patterson to comment on how the NIH will approach the issues of reproducibility and rigor.  Dr. Patterson indicated that many of the details in this regard will be released in the coming months.  The issue of stem cell authentication is fundamental; the RMIP will be working with awardees to have their stem cells (both the source product and the final clinical product) fully characterized.  The RMIP will also work with investigators to identify what types of assays and characterization would be most helpful to the field while making that data available to the community at large.

Dr. Oro thanked Dr. Patterson for her leadership and suggested that the NIAMS has a unique opportunity to make a significant difference in this space.  He asked how best to increase the visibility and raise awareness of the RMIP.  Dr. Katz noted that intramurally, the Institute has made a large investment in a Center for Cellular Engineering.  He acknowledged the challenges associated with publicizing the RMIP and its associated opportunities.  Dr. Patterson added that highlighting progress made by RMIP-funded projects is one way to highlight the program; professional societies and patient groups can also play an important role.

Dr. Patterson discussed the matching funds concept, explaining that these matching funds can take the form of in-kind contributions such as personnel time, resources, and other forms of institutional support (e.g., support from foundations, industry, etc.).

Dr. Elbaor asked about cell replication, noting that stimulating cell replication at the cartilage level in the joints would be a significant breakthrough.  He asked how individuals such as Council members can engage with this effort and help organize a program to stimulate private funding.  Dr. Patterson noted that there is no currently organized way to leverage patient and other groups as part of this effort.  Individual investigators could reach out to these entities, and additional thought is needed in this area.  In addition to needing the research community to be aware of the RMIP, patient engagement will be critical for understanding the sustainability of some of these interventions.  Patient communities will have an important role to play in terms of understanding the long-term effects of some of these interventions.  Dr. Katz noted that the Epidermolysis Bullosa Foundation and others have been active in promoting this type of work.  Dr. Oro added that partnerships between patient foundations, investigators, and industry are critical—these are the three stakeholders involved in developing therapies.

Dr. Katz commented that Dr. Patterson’s leadership has demonstrated NIH’s serious commitment to reproducibility and rigor—any group funded by the RMIP will need to include validation from a separate group.  Dr. Patterson noted that this summer, the RMIP will be reaching out to the community to solicit input on how this validation will be carried out and will be developing a proposed approach.  She also discussed the importance of sharing data in this space.

Dr. Khosla discussed using iPS cells as disease models and developing small molecules, suggesting that this may be the future of regenerative medicine.  He asked if this type of approach has been considered.  Dr. Patterson noted that this type of approach has been discussed within the RMIP.  She also explained that the RMIP will also be supporting projects that capitalize on innate or endogenous stem cells and recruiting, reprogramming, and attracting them into sites while coupling this with a matrix that has small molecules that can act on them. 


Dr. Boyce explained that the goals of RISK Program are to support: (1) highly innovative and significant ideas in their infancy, (2) ideas that are beyond the regular R21 mechanism, (3) applications of high potential value that may not fare well otherwise in peer review, and (4) disease-focused translational studies.  The NIAMS is seeking applications that are risky, premature, controversial, and/or unconventional.  Applicants do not need to have preliminary data or extensive background material.  Dr. Boyce explained that, in 2016, the NIH Office of Extramural Research published a paper on NIH peer review scoring behavior.  The Approach, and to a lesser extent the Significance criterion scores, were the main predictors of an R01 application’s likelihood of being funded.  The Institute reviewed NIAMS R01 and R21 (exploratory and experimental) applications, and came to the same conclusion. 

Dr. Boyce explained that the RISK Program’s challenge is to help the Institute select truly innovative and significant ideas for funding through a focused peer review approach.  The two primary peer review was focused in this regard was to:

  • Review concepts separately from feasibility, in two separate stages.  For X02 applications, only innovation and significance are reviewed with no overall impact score.  Select applicants from the X02 pool were invited to submit a full R61/R33 application; these were reviewed for feasibility.
  • Utilize applicant anonymity (a first at the NIH) for the X02 applications.

In late 2016, the NIAMS released two sets of FOAs, one on skin and rheumatic diseases and one on musculoskeletal diseases.  Dr. Boyce explained that the X02 application is strictly the presentation of an idea, and as such, the general concept is reviewed.  This 3-page application includes the project title and a research essay that includes Concept Summary, Innovation, and Significance sections.  Applications must conceal personal and institutional identities.  Dr. Boyce described the X02 peer review process, noting that applications are reviewed by mail, with no discussion among the reviewers.  As noted previously, only Significance and Innovation are reviewed, with special review criteria.  Applicants receive a summary statement with Significance and Innovation scores and comments (again, no overall impact score is given).  Applicants with pre-applications rated most highly innovative and relevant to the RISK program (based on reviewers’ individual evaluations and program officers’ recommendations) are notified of the opportunity to submit an R61/R33 application.

Dr. Boyce then described the R61/R33 application, noting that this award is the idea testing and exploration step.  This mechanism is a two-phase process.  In the R61 phase, the applicant must propose critical experiments for unambiguously testing the innovative idea and must explicitly set milestones for gauging the success of the R61 phase.  Funding for this phase is up to $250,000 per /year for 2 years.  In the R33 phase, awards are contingent on the milestone results of the R61 phase.  The R33 is for further exploration if the innovation is promising (it is expected that not all applicants will be awarded the R33 phase), with funding at up to $250,000 per year for 1 year.  The R61/R33 peer review meeting is a traditional face-to-face meeting with reviewer discussion.  In addition to the standard review criteria, there are special review criteria for Significance, Innovation, and Approach.  There is also an additional review criterion for transition milestones to the R33 Phase.  Applicants receive a summary statement with scores for all review criteria, as well as an overall impact score.

ESI status is eliminated for those ESIs receiving the R61 award (with or without the R33 extension).  An X02 pre-application that is “successful” (i.e., invited to apply for the R61/R33) will not affect ESI status.  Multi Principal Investigator (PI) applications are allowed, but discouraged for ESIs.

Dr. Boyce presented some early data from the RISK Program.  The response was similar between the skin and rheumatic and musculoskeletal FOAs.  Roughly 47% of X02 applications reviewed were invited to submit the full R61/R33 application.  Of the R61/R33 applications reviewed, about 18% were awarded.  While around half of X02 applicants had never had a substantial NIH grant, those invited to submit the R61/R33 and ultimately awarded the R61/R33 were predominantly established NIH investigators; of the 14 R61/R33 awardees, only one of these PIs had not received previous NIH funding.  Dr. Boyce suggested that this may reflect skill and experience in grant writing.  In terms of applicant faculty position and success, the distribution of assistant, associate, and full professor were nearly unchanged from X02 applicants to R61/R33 invitees.  This may be because of anonymous review.  The large majority (almost 80%) of R61/R33 awardees were full professors.  With regard to overall score-driving criteria, Dr. Boyce highlighted a few trends.  Approach scores still drove the overall R61/R33 score.  However, Innovation correlated slightly more with overall score higher for RISK applications, and Investigator and Environment correlated less.  She characterized these trends as a successful demonstration of the focused peer review approach.

Dr. Boyce then shared reviewer feedback, noting that most reviewers felt that anonymity was achieved in the X02 applications, felt that anonymous review was helpful in objectively evaluating an application’s significance and innovation, and supported the X02 mechanism and anonymous review.  Reviewers also commented that a lack of information on research strategy makes evaluating the innovation and significance of the project a challenge.  The variability regarding details provided made comparing applications a challenge, and it was suggested that a standardized template will help facilitate future reviews.

After summarizing the skin and rheumatic and musculoskeletal R61/R33 awards, Dr. Boyce outlined next steps with regard to re-issuing the RISK Program.  Plans to potentially re-issue RISK for FY 2019 have been posted to the NIAMS website.  Dr. Boyce summarized that:

  • X02 applicants were evenly distributed across career stage, but R61/R33 awards favored established NIH investigators/full professors.
  • Preliminary data suggest that the NIAMS was able to redirect reviewer focus to Innovation and away from Investigator and Environment.
  • Reviewers were supportive of the X02 anonymous review.
  • The NIAMS plans to re-issue this opportunity, with changes informed by the RISK pilot.


Dr. Katz clarified that the X02 review was a mailed review, and so the discussions that would have taken place during a first review may not have carried over to the second review.  Dr. Tseng added that the Institute tried to invite most reviewers from the X02 phase back to review the R61/R33 phase.

Dr. Holers expressed enthusiasm for the RISK Program and voiced support for the re-issue.  He asked if the reviewers felt that the applications would not have fared well in the R21 setting.  Dr. Holers also noted that mid-stage investigators and ESIs appeared to score well during the scoring of anonymous applications.  Dr. Boyce explained that there was a much greater emphasis on innovation due to more aggressive reviewer training for the musculoskeletal reviews as compared with the skin and rheumatic reviews.  Dr. Katz commented that roughly 6 years ago, the Institute made a concerted effort to get its R21s to focus on innovative research projects.  Investigators were asked to contact NIAMS Program Directors for guidance.  This effort was not successful, leading the Institute to establish the RISK Program. 

Dr. Lester noted that the reviewers were able to identify applications that were too similar to an R01 application (e.g., there was too much data, there was too much confidence in the data, etc.), and her impression is that reviewers understood the Institute’s intent to identify risky projects that would not fare well in a standard Center for Scientific Review study section.

Dr. Econs indicated that equal cohorts are not being compared when ESIs are compared with established investigators.  He suggested that it may not be possible to achieve equality in terms of success rates between the two groups.  Grantsmanship may play a role, but it also relates to having the experience and ability to develop a well thought-out plan. 

Dr. Tapscott asked about whether the Institute looked at whether funded RISK projects came from previously rejected R01 applications.  Dr. Boyce explained that this analysis was carried out; some of the applications appeared to come from recycled R01 and R21 applications, but none of these were funded as RISK awards.

Dr. Tseng explained that one of the challenges associated with risk-taking projects is gauging success.  The goal of the RISK Program is to increase the funding of innovation, but identifying an adequate, standardized measure of innovation represents a significant challenge.  Dr. Tseng referenced the book Conceptual Revolutions by Paul Thagard, a philosopher of science whose interests focus on how concepts are formed and evolve during scientific investigation.  In his book, he provides nine grades for the degree of change in concept, starting with one (adding a new instance) and progressing through nine (changing the organizing principle of a hierarchical tree).  Dr. Tseng and colleagues applied this framework to 100 community-defined discoveries from 1948-2015 and found that the discoveries that scored higher tended to include more Lasker Award and Nobel Prize-winning PIs (J. Infometrics. Feb 2017:11;46-62).  After some preliminary analyses based on applying the Thagard Scale to RISK applications, Dr. Tseng reported that most of these applications would be scored either 4 (adding a new part-relation) or 5 (adding a new kind-relation) largely because these applications are focused on combating disease, not on foundational discoveries.  Dr. Khosla suggested that these scores may be appropriate for funded RISK applications.  Dr. Tseng explained that to fully apply the Thagard Scale to RISK and other applications, several issues need to be resolved, such as resolving the proposal versus the published conclusion, discovery versus method (intervention), and characterization/screening versus hypothesis testing.  He also noted that a future NAMSAC meeting could include a presentation on the full application of the Thagard Scale to RISK applications.


Dr. Bianchi explained that NICHD’s name is somewhat of a misnomer in that many people assume this Institute funds almost all of the NIH research related to child health; however, the NICHD only funds about 18% of that research.  Overall, roughly 55% of NICHD’s $1.4 billion budget is allocated to child health, 40% is dedicated to reproductive health, and approximately 5% of the NICHD budget goes to the National Center for Medical Rehabilitation Research (NCMRR), which supports adult and pediatric research.  

Dr. Bianchi noted that majority of open NIH funded phase 3 and phase 4 clinical studies specifically exclude pregnant and lactating women as well as children.  Some explicitly exclude people with intellectual disabilities; many do not reference this population at all.  This current approach effectively excludes 58% of the U.S. population.  The NICHD is working on changing the culture and moving towards inclusion.  NIH rules and regulations will change in January 2019 to require investigators to explain how they are including children in their research or explain why they are not explaining children in their research. 

The NICHD is about to embark on a strategic planning process to determine the Institute’s scientific priorities moving forward and align resources with these priorities.  Dr. Bianchi described the workplan for the strategic planning process, which will include experts from within and external to the NIH.  Updates will be posted on NICHD’s website.

With regard to enhancing collaboration between the NIAMS and NICHD, Dr. Bianchi provided examples in the following areas:


  • Pediatrics.  The Trans-NIH Pediatric Research Consortium was scheduled to meet for the first time later this day and has been tasked with: (1) harmonizing efforts in child health research across the 27 NIH ICs; (2) identifying gaps and opportunities for collaboration; (3) enhancing communication between NIH, advocacy groups and Capitol Hill; (4) conducting an outreach effort to encourage senior pediatric researchers to serve on review panels; and (5) providing trans-NIH supported training to grow pediatric work force.  Pediatric research is funded by virtually every NIH Institute (the NIAMS spent roughly $70 million, or 12.5% of its budget, on pediatric research in FY 2017).  Dr. Bianchi noted that $4.2 billion in NIH funds are being put towards pediatric research, yet there is no mechanism to strategically review this portfolio and identify overlaps between ICs.
  • Pregnancy and Lactation.  The 21st Century Cures Act mandated the creation of the Task Force on Research Specific to Pregnant Women and Lactating Women to address: (1) existing Federal efforts and programs to understand the health effects on pregnant and lactating women, and related birth and pediatric outcomes; (2) research collaboration potential; (3) ethical issues surrounding inclusion of pregnant and lactating women in clinical research; and (4) effective communication strategies with health care providers and the public.  The Task Force has met four times, and is developing a report due to HHS in September 2018.  A total of 15 recommendations have been generated.  The central focus of these recommendations is aimed at changing the culture that has significantly limited scientific knowledge of therapeutic product safety, effectiveness, and dosing for pregnant and lactating women.  Additionally, Dr. Bianchi noted that pregnant women have been historically excluded from Clinical Center studies.  A working group has been formed to examine the benefits and risks of having healthy pregnant women participate in research protocols at the NIH Clinical Center.
  • Rehabilitation.  Dr. Bianchi noted that the NICHD works closely with a number of NIAMS-funded investigators through the NCMMR.  NIAMS Orthopaedic Research Program Director Dr. Chuck Washabaugh co-chairs the Trans-NIH Medical Rehabilitation Coordinating Committee.  The NIAMS is co-funding a study examining the mechanisms underlying contractures and potential targets for treatment and rehabilitation in Duchenne muscular dystrophy (DMD) and other neuromuscular conditions.  Additionally, there is a publication in press developed by a number of federal collaborators (including the NIAMS) highlighting NIH interests in rehabilitation to augment use of regenerative medicine, particularly in volumetric muscle loss following traumatic injury (Dr. Fei Wang, Musculoskeletal Tissue Engineering and Regenerative Medicine Program Director, is leading this work for the NIAMS).
  • Muscular Dystrophies.  Dr. Bianchi noted that the NIAMS and NICHD are both charter members of the Muscular Dystrophy Coordinating Committee.  The NICHD supports two Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Centers (at the University of Massachusetts Medical School and the University of Texas Southwestern).  The NICHD also supports investigator-initiated grants on genetic screening and therapies for nemaline myopathies at Harvard University and a small business award for newborn screening of Duchenne and congenital muscular dystrophies.
  • Bone Health.  Currently, the main collaborations in this area appear to intramural in nature.  Dr. Bianchi described a joint project between the NIAMS, NICHD, and Institute of Osteology that found that somatic activating mutations in MAP2K1 cause melorheostosis.  Drs. Bhattacharyya and Siegel have been leading this effort on behalf of the NIAMS.  Of 15 patients who underwent paired biopsies of affected and contralateral unaffected tissue, 8 were found to have somatic mutations in the negative regulatory domain of MAP2K1.    

Dr. Bianchi also suggested a number of opportunities for future collaboration, including:

  • Strategic analysis of opportunities through the Trans-NIH Pediatric Research Consortium.
  • Research on the use of topical medications by pregnant and lactating women, especially for dermatologic conditions.
  • Taking a lifespan approach to bone health (e.g., the effects of childhood obesity on musculoskeletal health).
  • In the area of rehabilitation: (1) non-pharmacologic or combination approaches to pain that include rehabilitation strategies; (2) re-competition of rehabilitation infrastructure network, which currently includes kinematics and regenerative rehabilitation centers; and (3) training and career development focus on rehabilitation professionals, particularly physical therapy and physical rehabilitation medicine.
  • Newborn screening, particularly newborn screening for DMD (the NICHD is working with the muscular dystrophy community to build the evidence base for adding DMD to the recommended national newborn screening panel).
  • Spinal muscular atrophy.


Dr. Katz asked about what age range the NICHD considers in terms of pediatrics.  Dr. Bianchi explained that the NICHD does not have an age cut-off because it funds both pediatric and adult research.  The NIH definition recently changed to include those aged 18 and younger. 

Dr. Buyon suggested that the NIAMS could work with the NICHD to make contributions in the area of maternal screening, not just neonate screening.  She further suggested that the NIH consider autoantibodies and autoimmunity as a maternal environmental factor.  Screening for many autoantibodies could have a significant impact on pregnancy and the cost of many of these tests is significantly lower than the costs associated with genetic screening.  Dr. Bianchi agreed and noted that this area has not yet been capitalized upon and that the NICHD would be open to exploring opportunities in this area. 


This portion of the meeting occurred during closed session.


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 934 primary and secondary applications. The total cost requested in year -01 for all applications was $363,759,500.



The 95th 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

Stephen I. Katz, M.D., Ph.D.
Chairman, National Arthritis
and Musculoskeletal and Skin
Diseases Advisory Council

Director, National Institute of
Arthritis and Musculoskeletal and
Skin Diseases

Last Reviewed: