June 7, 2016

Department of Health and Human Services
Public Health Service
National Arthritis and Musculoskeletal and Skin Diseases Advisory Council

Minutes of the 89th Meeting
8:30 a.m. to 3:55 p.m.

June 7, 2016 Council Minutes Webcast


    The 89th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on June 7, 2016, at the National Institutes of Health (NIH) Campus, Building 31, Conference Room 6. 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
    Ms. Magdalena Castro-Lewis
    Dr. V. Michael Holers
    Dr. Sundeep Khosla
    Dr. Gary A. Koretzky
    Dr. Ethan Lerner
    Dr. William Mulvihill
    Dr. Martha M. Murray
    Dr. Amy Paller
    Dr. Grace Pavlath (via teleconference)
    Dr. Anthony E. Rankin
    Dr. Christy I. Sandborg
    Mr. Richard F. Seiden
    Dr. Elizabeth Shane
    Mr. Alexander Silver
    Dr. Stephen J. Tapscott
    Dr. Gwendolyn L. Powell Todd

    Staff and Guests

    The following NIAMS staff and guests attended:


    Dr. Lee Alekel
    Mr. Steve Austin
    Dr. Carl Baker
    Ms. Pamela Beheler
    Mr. Paul Berry
    Ms. Elizabeth Bouras
    Dr. Amanda Boyce
    Mr. Gahan Breithaupt
    Dr. Stephanie Burrows
    Ms. La’Tanya Burton
    Ms. Justine Buschman
    Dr. Robert Carter
    Dr. Faye Chen
    Ms. Jennifer Chi
    Dr. Thomas Cheever
    Dr. Ricardo Cibotti
    Ms. Theresa Do
    Dr. Jonelle Drugan
    Ms. Barbara Footer
    Dr. Nancy Garrick
    Ms. Gail Hamilton
    Ms. Sarah Hwang
    Dr. Chao Jiang
    Ms. Katie Joffee
    Mr. Andrew Jones
    Dr. Stephen I. Katz
    Ms. Shahnaz Khan
    Ms. Stephanie Kreider
    Mr. Mark Langer
    Dr. Gayle Lester
    Dr. Helen Lin
    Ms. Anita Linde

    Ms. Leslie Littlejohn
    Dr. Yin Liu
    Ms. Mimi Lising
    Dr. Kan Ma
    Dr. Marie Mancini
    Dr. Su-Yau Mao
    Dr. Kathryn Marron
    Dr. Joan McGowan
    Ms. Leslie McIntire
    Dr. Laura K. Moen
    Ms. Melinda Nelson
    Dr. Kristy Nicks
    Dr. John O’Shea
    Ms. Reaya Reuss
    Ms. Trish Reynolds
    Dr. Kathy Salaita
    Dr. Susana Serrate-Sztein
    Dr. William Sharrock
    Ms. Sheila Simmons
    Ms. Robyn Strachan
    Dr. Dena Sumaida
    Ms. Yen Thach
    Ms. Jamie Thompson
    Dr. Hung Tseng
    Ms. Christine Tsui
    Dr. Bernadette Tyree
    Dr. Fei Wang
    Dr. Xibin Wang
    Dr. Yan Wang
    Dr. Chuck Washabaugh
    Dr. James Witter
    Dr. Xincheng Zheng


    Mr. John Burklow, Associate Director for Communications and Public Liaison, NIH
    Mr. Mike Bykowski, Consolidated Solutions and Innovations
    Ms. Sara Chang, Lupus Foundation of America
    Dr. Guy Eakin, Arthritis Foundation
    Ms. Ann Elderkin, American Society for Bone and Mineral Research
    Ms. Patti Brandt Hansberger, Office of Legislative Policy and Analysis, Office of the Director, NIH
    Ms. Anna Hyde, Arthritis Foundation
    Ms. Kim James, IQ Solutions
    Dr. Lynne Jones, Orthopaedic Research Society
    Dr. Roger Kaspar, TransDerm, Inc.
    Dr. Petra Kaufmann, Office of Rare Diseases Research, NIH
    Dr. Rajiv Kumar, Center for Scientific Review, NIH
    Dr. Michael Lauer, Deputy Director for Extramural Research, NIH
    Dr. Kayla Lindsay, Arthritis Foundation
    Dr. Sarah Martin, Sjogren’s Syndrome Foundation
    Mr. Blake McDonald, American Acadamy of Dermatology Association
    Dr. Sherry Mills, Office of Extramural Programs, NIH
    Dr. Lynn Mirigian, American Society for Bone and Mineral Research
    Mr. Nate Robinson, IQ Solutions
    Mr. Robert Riggs, Scleroderma Foundation
    Ms. Kirstie Saltsman, IQ Solutions
    Mr. Taylor Scott, Nevus Outreach, Inc.
    Mr. Joseph Stewart, Marfan Foundation
    Ms. Susan Thornton, Cutaneous Lymphoma Foundation
    Ms. Jennifer Tripp, Muscular Dystrophy Association
    Ms. Mary Wheatley, American College of Rheumatology
    Ms. Randi Williams, KAI Research, Inc.


    A motion was made, seconded, and passed to approve the minutes of the 88th NAMSAC meeting, held on February 2, 2016.


    Future Council meetings are currently planned for the following dates:

    September 13, 2016
    January 25, 2017
    June 21, 2017
    September 6, 2017
    February 7, 2018
    June 12, 2018
    September 5, 2018


    Dr. Katz began his Director’s Report by reminding Council members that the public portion of this NAMSAC meeting was being videocast. More than 110 people viewed the February 2016 NAMSAC meeting live or afterward.

    Personnel Changes at the NIH

    • Dr. Patricia Brennan has been appointed Director of the National Library of Medicine. Dr. Brennan will be leaving the University of Wisconsin-Madison to assume her new position this summer.
    • Dr. Eric Dishman has been named as Director of the Precision Medicine Initiative. Most recently, Dr. Dishman served as Vice President and Intel Fellow of Intel Corporation’s Health and Life Sciences Group.
    • Dr. Matthew Gillman has been selected as the Environmental Influences on Child Health Outcomes Program Director, which is a follow-up to the National Children’s Study. Dr. Gillman comes to the NIH from Harvard Medical School.
    • The NIH currently has searches underway for the Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development as well as for the Director of the National Institute of Mental Health.

    Congressional Interactions

    NIAMS participated in two congressional events. The first, organized by the Alliance for Lupus Research and the Lupus Research Institute, focused on the new NIH Action Plan for Lupus Research (developed by NIAMS on behalf of the NIH), was well attended. The second event was sponsored by the American Academy of Orthopaedic Surgeons (AAOS). As it does on an annual basis, the AAOS brought patients, physicians, and researchers to Washington to educate Congress about the impact of orthopaedic conditions on individuals and society and about the value of medical research.

    NIH and NIAMS Activities

    Dr. Katz reminded Council members of last year’s report of serious deficiencies in the NIH Clinical Center’s Pharmaceutical Development Section and the swift action taken by Dr. Collins to address the issues. Last month, in response to recommendations from a working group of the Advisory Committee to the Director, Dr. Collins established a new hospital board for the NIH Clinical Center. As part of its responsibilities, the board will advise the NIH on policies and organizational approaches that promote quality and patient safety.

    Dr. Katz also noted that discussions during a past NAMSAC meeting were helpful when the Institute deliberated about how best to restructure its R03 grant program. He thanked Council for their input, and pointed out that the restructured funding opportunity was published in May. It can be viewed here.

    As part of the NIAMS scientific planning process, the Institute held its annual extramural scientific training session on April 29, 2016. Under the guidance of Drs. Joan McGowan (Division of Musculoskeletal Diseases Director), Susana Serrate-Sztein (Division of Skin and Rheumatic Diseases Director), and Laura K. Moen (Division of Extramural Research Activities Director), NIAMS Program Directors, Scientific Review Officers, and other NIH staff discussed:

    • Data that staff could consider when proposing topics that might benefit from targeted FOAs
    • Strategies to facilitate the transition of mentored K01 awardees into successful, independent investigators
    • How the NIAMS rehabilitation medicine portfolio complements and can leverage the NIH Rehabilitation Research Plan

    These topics will be discussed at a future NAMSAC meeting.

    Dr. Katz also noted that on June 6th, the NIAMS held roundtable discussion on ichthyosis organized by Drs. Carl Baker and Ricardo Cibotti (Program Officers in the NIAMS Division of Skin and Rheumatic Diseases). Fifteen scientists from around the country—including some from the NIH Intramural Research Program, the U.S. Food and Drug Administration, and other Institutes—discussed scientific opportunities, knowledge gaps, barriers, and unmet needs related to: (1) ichthyosis pathogenesis; (2) therapeutics, including the development of drug targets; and (3) clinical research.

    Highlights of Selected Recent Scientific Advances

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

    • Separate studies by Dr. Earl Carsten’s group at the University of California, Davis and Dr. Wolfgang Liedtke’s team at Duke University showed that mice lacking TRPV4 could still sense itch that was provoked by certain chemicals, but not others. (J Invest Dermatol. 2016 Jan;136(1):154-60. doi: 10.1038/JID.2015.388. PMID: 26763435) and (J Biol Chem. 2016 May 6;291(19):10252-62. doi: 10.1074/jbc.M116.716464. Epub 2016 Mar 9. PMID: 26961876).
    • Dr. Katz noted that hair stem cells provide an effective model for how cell proliferation can be turned on and turned off, and described recent work by two NIAMS grantees, Dr. Rui Yi at the University of Colorado, Boulder, and Dr. Elaine Fuchs at Rockefeller University. Their work identified a key regulatory protein that helps activated hair follicle stem cells return to quiescence during the growth phase of the hair cycle and may also lead to new drug targets to treat hair loss and slow hair changing associated with aging (Science. 2016 Feb 5;351(6273):613-7. doi: 10.1126/science.aad5440. PMID: 26912704) and (Proc Natl Acad Sci USA. 2016 Mar 15;113(11):E1506-15. doi: 10.1073/pnas.1601569113. Epub 2016 Feb 24. PMID: 26912458).
    • A recent paper by groups led by Drs. Melissa Spencer and April Pyle of the University of California, Los Angeles describes a strategy using CRISPR technology to advance muscular dystrophy research. (Cell Stem Cell. 2016 Apr 7;18(4):533-40. doi: 10.10/1016/j.stem.2016.01.021. Epub 2016 Feb 11. PMID: 26877224).
    • Another publication, by Dr. Peter Jones at the University of Massachusetts Medical School, introduces a proof-of-concept for use of the CRISPR/Cas9 system in facioscapulohumeral muscular dystrophy (FSHD). The research team used the approach to target epigenetic modifiers and repress the aberrantly expressed gene sequence in cultured FSHD myocytes (Mol Ther. 2016 Mar;24(3):527-35. doi: 10.1038/mt.2015.200. Epub 2015 Nov 3. PMID: 26527377).
    • Dr. Ivo Kalajzic and his team at the University of Connecticut Health Center have identified a muscle stem cell population responsible for abnormal bone function. (Bone 2016 Mar;84:69-77. doi: 10.1016/j.bone.2015.12.010. Epub 2015 Dec 22. PMID: 26721734).
    • Two recent mouse studies involving NIAMS grantee Dr. Frederick Kaplan and others at the University of Pennsylvania identified several drug candidates targeting two different aspects of heterotropic ossification in FOP:
      • The cellular response to low oxygen levels brought about by inflammation (J Bone Miner Res 2016 Mar 30. doi: 10.1002/jbmr.2848. [Epub ahead of print] PMID: 27027798)
      • The cartilage formation that occurs during ossification (J Bone Miner Res. 2016 Feb 20. doi: 10.1002/jbmr.2820. [Epub ahead of print] PMID: 26896819).
    • A research group studying ankylosing spondylitis led by Dr. Michael Ward in the NIAMS Intramural Research Program’s Clinical Trials and Outreach Branch found that fusion most often begins in the back part of the vertebrae. This area of the spine bears the most weight, which suggests that physical loading may contribute to the fusion process. If mechanical stress is a factor in disease progression, it may be possible to find interventions that delay fusion (Ann Rheum Dis. 2016 Jan 21. doi: 10.1136/annrheumdis-2015-208802 [Epub ahead of print] PMID: 26797721).
    • Drs. Jeff Katz and Elena Losina’s team at Brigham and Women’s Hospital has found that the use of opioids provided less benefits than the use of the nonsteroidal anti-inflammatory drug (NSAID) naproxen in older people who have heart disease and diabetes. No advantage was seen in the use of the prescription NSAID Celebrex. This finding challenges physicians’ reluctance to use NSAIDs in patients who have multiple comorbidities and has implications for research, policy, and practice (Osteoarthritis Cartilage. 2016 Mar;24(3):409-18. doi: 10.1016/j.joca.2015.10.006. Epub 2015 Oct 23. PMID: 26525846).
    • NIAMS grantees Drs. Jennifer Anolik and Lianping Xing at the University of Rochester discovered the link between B cells and bone destruction when they demonstrated that B cells promote the development of osteoclasts (the cells that destroy bone mineral during bone turnover) by producing a signaling molecule called RANKL. (Arthritis Rheumatol. 2016 Apr;68(4):805-16. doi: 10.1002/art.39489. PMID: 26554541).
    • Work by a team of researchers that includes Dr. Marcus Clark at the University of Chicago and Dr. Michelle Petri at Johns Hopkins University demonstrated that IgE antibodies, which until recently were thought to be limited to allergic responses, can activate triggers leading to lupus. (Nat Immunol. 2016 Feb;17(2):196-203. doi: 10.1038/ni.3326. Epub 2015 Dec 21. PMID: 26692173).
    • Dr. Virginia Pascual and colleagues at the Baylor Institute for Immunology Research are also studying the molecular mechanisms that cause plasmacytoid dendritic cells to produce interferon. In lupus, neutrophils are not able to remove the reactive oxygen species before the molecules exit the cells. Dr. Pascual’s group showed that release of the oxidized molecules activates the plasmacytoid dendritic cells and triggers interferon release (J Exp Med. 2016 May 2;213(5):697-713. doi: 10.1084/jem.20151876. Epub 2016 Apr 18. PMID: 27091841).

    Communication and Outreach Highlights

    Dr. Katz reminded Council members that the dissemination of information on research progress is a key component of the NIAMS mission. He mentioned several recent activities including:

    • A bilingual Facebook Chat that NIAMS hosted, featuring Dr. McGowan and Dr. Lee Alekel (Program Director in the Division of Musculoskeletal Diseases), in recognition of Osteoporosis Awareness month.
    • A webinar on the Patient-Reported Outcomes Measurement Information System (PROMIS®) that Dr. Carter and Dr. James Witter (of the NIAMS Division of Skin and Rheumatic Diseases) presented to members of the NIAMS Coalition.

    Dr. Katz reminded Council members that they can access announcements that the Institute shares through its monthly NIAMS Update newsletter.


    Council members commented on the science advances, noting that some provide clear evidence that the Institute’s investment in basic science is resulting in approaches that impact disease.

    Dr. Katz asked Council members for feedback on the STAR Program, including whether eligibility should continue to include investigators with other R01s, or those who do not meet the NIH criteria for early stage investigators (i.e., those within 10 years of their post-doctoral training). Points raised by Council members covered the original intent of the STAR program, concerns regarding the scope of the STAR award, and a suggestion for further analysis with a suitable comparator group.

    Dr. Katz then turned the discussion to a New York Times article on osteoporosis that focused on the reluctance of patients to use bisphosphonates. The article pointed out that the ASBMR, the National Osteoporosis Foundation, and the National Bone Health Alliance issued an urgent call for doctors to be more aggressive in treating patients at high risk and for patients to be more aware of the need for treatment.

    Council member Dr. Sundeep Khosla (Dr. Francis Chucker and Nathan Landow Research Professor, Director of the Mayo Clinic Center for Clinical and Translational Science, and Dean for Clinical and Translational Science at Mayo Clinic College of Medicine) and Council member Dr. Elizabeth Shane (Professor of Medicine and Vice-Chair for Clinical and Epidemiological Research at Columbia University College of Physicians and Surgeons) led the discussion that followed. The research findings in the article were discussed as were suggestions for an NIH/NIAMS role in challenging misperceptions about bisphosphonate use.


    Dr. Petra Kaufmann, Director of the Office of Rare Diseases Research and Director of the Division of Clinical Innovation at the National Center for Advancing Translational Sciences (NCATS), provided Council members with an update on the Clinical and Translational Science Award (CTSA) program. She noted that now is an exciting time for academic research and academic medical centers, but also a challenging time, because there are a number of changes underway with regard to the healthcare system, digitalization of medicine, and expectations on the part of patients and communities, who are no longer satisfied to be passive consumers of research. Patients now want and expect to play a more active role in determining research directions. Advances in basic research present numerous opportunities to help address these challenges, but the current system generally does not allow for the rapid translation of discoveries into health benefits.

    Dr. Kaufmann described the ways in which the CTSA Program is shifting its vision and priorities for creating an efficient collaborative national network for translational medicine. The intent is to:

    • Create a platform of excellence for multisite studies
    • Promote innovation for smarter data systems, operations, and participant recruitment
    • Free resources and time to generate medical evidence at a faster pace
    • Create a national, harmonized network to support NIH studies through shared data models, quality and training standards, streamlined processes, harmonized ethics frameworks, and results-based accountability
    • Train the next generation of translational researchers

    Dr. Kaufmann summarized her remarks with the following points:

    • A coordinated learning health system that integrates care and research is needed.
    • The CTSA Program is a vital player in leading this change.
    • The CTSA Program’s strength as a national network can help translate discoveries into health benefit through efficiency, quality, training, and aligning academic and societal needs.
    • Coordination and collaboration are critical.
    • The CTSA Program will play a critical role in transforming the current system to meet 21st century needs.


    Dr. Katz noted that during the discussions leading to the formation of the CTSA Program, it was felt that measuring how the Program accelerates and enhances activities at the Institute level may be an appropriate evaluation measure. He added that a number of CTSA PIs are or have been rheumatologists, bone biologists, and dermatologists.

    Council members expressed interest in what they perceived as improvements moving forward for the CTSA Program. They mentioned that integration of non-profit organizations can play a role in patient recruitment. Council also noted that emphasizing the role of advocacy groups could be useful since these groups are now playing a significantly larger role in funding research and driving research progress. The CTSA Program can collaborate with and build upon the work of these organizations.


    Dr. Mills explained that the NIH receives more meritorious applications for research funding than it is able to support. Select pay can be used to fund a few of the meritorious projects not selected for funding during peer review that align with an IC’s mission, or applicants can be asked to revise and resubmit their applications. OnPAR, which will reach the end of its pilot this fall, represents an alternative approach for supporting applications that NIH cannot fund through a global public-private partnership with the Leidos Corporation.

    She explained that OnPAR’s goal is to match high-quality biomedical research project applications with the priority areas of interest of funding agencies, private foundations, and pharmaceutical and biotechnology companies. Dr. Mills noted that OnPAR hopes to engage with non-profit entities as well.

    Dr. Mills described the application process and identified the current members. OnPAR will provide access to a pipeline of research project applications that can either supplement members’ internal projects or provide innovative new ideas for future medical research. OnPAR generally considers unfunded grant applications that scored within the 30th percentile in the NIH peer review process and have been reviewed in the last 12 months.

    Dr. Mills encouraged those interested in additional information to contact OnPAR@leidos.com and directed those with NIH-specific questions to OEPmailbox@od.nih.gov.


    Council members were enthusiastic about the OnPAR approach, and several had specific suggestions for new members in this effort. Dr. Katz indicated that the NIAMS will consider adding language to its funding plan to indicate that OnPAR is available as an option.


    Dr. Michael Lauer drew Council members’ attention to a recent article in which the authors lamented the fact that a number of universities and/or departments advertise their research in terms of the number of NIH grants or amount of NIH funding that they received (Proc Natl Acad Sci USA. 2015 Aug 4;112(31):9496-7. doi: 10.1073/pnas.1509005112. PMID: 26243873). The authors pointed out that a university claiming to be a "$200 million per year operation" is similar to an airline stating that "we spend more money transporting passengers than anybody else," or "we burn more gasoline than anybody else." Dr. Lauer noted that one airline’s mission and purpose has remained unchanged since 1971—"to deliver people where they want to go, safely, on time, with their bag, and with a smile…With low fares and no hidden fees." He commented that this is a profound statement in that each element is meaningful, objective, quantifiable, and verifiable.

    Dr. Lauer presented data on the number of unique PIs supported by the NIH. He pointed out that measuring scientific output and the impact of scientific output remains a significant challenge, and there is no gold standard metric for doing so. He then described possible predictors of scientific output, noting that by far, the most important predictor of having highly cited papers from an NIH research project grant is project duration. Other major predictors include grant mechanism, first fiscal year of funding, and total award amount. He added that while a 10% increase in funding does not generally lead to a 10% increase in output, a 10% increase in project duration leads to more than a 10% increase in output. This lends credence to the argument that the NIH should identify ways to make funding more sustainable over time—even if it means PIs receive less funding per year.

    Dr. Lauer concluded his remarks with an explanation that the more scientists and programs that are funded, the more likely it is that there will be great discoveries. The NIH is now creating narratives that trace the development of transformative discoveries that were made possible through NIH funding. This activity will provide answers to questions such as: What kinds of grants and what kinds of researchers had the most influence on important discoveries? Were they supported through large grants or small grants? Were they Institute-initiated or investigator-initiated? From a higher-level perspective, this activity may help inform the NIH on how best to spend its research dollars.


    Council members had questions about the approach for developing narratives and asked how many paradigm-shifting studies had been identified. There were also questions about the impact of one’s mentor and how that could be tracked. Dr. Lauer emphasized that to maximize the chances of making transformative discoveries, the research portfolio should be as diverse and as large as possible. He noted that the number of laboratories the NIH currently funds has not changed for many years and commented that finding ways to enable more laboratories to be supported will increase the likelihood that cures will be found.


    Mr. John Burklow, NIH Associate Director for Communications and Public Liaison, opened his remarks by describing the mission of NIH’s Office of Communications and Public Liaison (OCPL). The Office supports the communications efforts of the NIH Director and other NIH leaders and coordinates across the 27 NIH Institutes and Centers as well as the NIH Office of the Director. It also coordinates across federal agencies and departments as well as with constituency organizations. The OCPL engages with reporters, editors, and producers. Additionally, it responds to public inquiries, oversees NIH-wide communications, responds to Freedom of Information Act requests, and manages special events. The strategic communication goals for OCPL are to: (1) create a consistent, clear, strong NIH identity; (2) maximize opportunities in traditional, web-based, and social media; (3) collaborate with grantee institutions to tell the NIH story; and (4) partner with outside organizations to communicate the value of biomedical research.

    Mr. Burklow explained that Dr. Collins is eager to heighten awareness of the NIH and make the best case possible for investing in biomedical research, and presented some examples. He noted that the recent media coverage of the Ebola and Zika viruses have provided the OCPL with opportunities to address research issues and explain the relevance of medical research and how it impacts people’s lives.


    Dr. Katz commented that the government shutdown in 2013 led to national exposure of the role the NIH, and particularly the Intramural Research Program. Council members acknowledged the efforts of the OCPL and NIAMS in communicating with underserved and multicultural groups, agencies, and communities. They suggested that the NIH give strong consideration to identifying how best to use the power of patients to promote the NIH and its work.


    In closed session, the Council reviewed a total of 714 applications requesting $1,046,274,771 in total costs and recommended 714 for $1, 1,046,274,771 in total costs. 38 applications were considered by early concurrence. For the record, it is noted that secondary applications were also considered en bloc.


    This portion of the meeting occurred during closed session.


    This portion of the meeting occurred during closed session.


    The 89th National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:55 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.

Laura K. Moen, Ph.D.
Executive Secretary, National Arthritis
and Musculoskeletal and Skin Diseases
Advisory Council

Director, Division 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: 06/07/2016