February 4, 2015

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

Minutes of the 85th Meeting
8:30 a.m. to 3:00 p.m.


    The 85th meeting of the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council (NAMSAC) was held on February 4, 2015, 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
    Dr. Sherine E. Gabriel
    Ms. Michelle Hofhine
    Dr. V. Michael Holers
    Dr. Sundeep Khosla
    Dr. Gary Koretzky
    Dr. Katherine Mathews
    Dr. Martha M. Murray
    Dr. Amy Paller
    Dr. Grace Pavlath
    Dr. Gwendolyn L. Powell Todd
    Dr. Christy I. Sandborg
    Mr. Richard F. Seiden
    Mr. Alexander Silver
    Ms. Elizabeth Smith
    Dr. Xiao-Jing Wang

    Staff and Guests

    The following NIAMS staff and guests attended:


    Ms. Alexandra Adams
    Dr. Lee Alekel
    Mr. Steven Austin
    Dr. Carl Baker
    Ms. Pamela Beheler
    Dr. Amanda Boyce
    Mr. Gahan Breithaupt
    Dr. Stephanie Burrows
    Ms. La'Tanya Burton
    Ms. Justine Buschman
    Dr. Robert Carter
    Ms. Jennifer Chi
    Ms. Robin DiLiello
    Dr. Jonelle Drugan
    Mr. Erik Edgerton
    Ms. Elizabeth Elliott
    Ms. Barbara Footer
    Dr. Nancy Garrick
    Ms. Katie Joffee
    Ms. Gail Hamilton
    Mr. Andrew Jones
    Dr. Stephen I. Katz
    Ms. Mary Beth Kester
    Ms. Shahnaz Khan
    Ms. Stephanie Kreider
    Ms. Colleen Labbe
    Mr. Mark Langer
    Dr. Gayle Lester
    Dr. Helen Lin
    Ms. Anita Linde
    Ms. Leslie Littlejohn
    Dr. Kan Ma

    Dr. Su-Yau Mao
    Dr. Marie Mancini
    Dr. Kathryn Marron
    Dr. Joan McGowan
    Ms. Sherry Meltzer
    Dr. Laura K. Moen
    Ms. Regina Mong
    Ms. Melinda Nelson
    Ms. Anna Nicholson
    Ms. Christine Ortega
    Dr. James Panagis
    Ms. Vivian Pham
    Ms. Reaya Reuss
    Ms. Trish Reynolds
    Dr. Kathy Salaita
    Dr. Susana Serrate-Sztein
    Dr. William Sharrock
    Ms. Sheila Simmons
    Ms. Allisen Stewart
    Ms. Robyn Strachan
    Ms. Yen Thach
    Ms. Jamie Thompson
    Dr. Phil Tonkins
    Dr. Hung Tseng
    Dr. Bernadette Tyree
    Dr. Fei Wang
    Dr. Xibin Wang
    Dr. Chuck Washabaugh
    Ms. Sara Rosario Wilson
    Dr. James Witter
    Dr. Xincheng Zheng


    Mr. Randy Beranek, National Psoriasis Foundation
    Mr. Michael Bykowski, Consolidated Solutions and Innovations
    Ms. Kim Cantor, Lupus Foundation of America
    Mr. Dane Christiansen, Health and Medical Council of Washington
    Mr. Quardricos Driskell, National Psoriasis Foundation
    Ms. Anna Hyde, Arthritis Foundation
    Ms. Kim James, IQ Solutions
    Ms. Annie Kennedy, Parent Project Muscular Dystrophy
    Dr. Joseph Laakso, Endocrine Society
    Mr. Simit Pandya, American Association of Orthopaedic Surgeons
    Mr. Nate Robinson, IQ Solutions
    Ms. Kirstie Saltsman, IQ Solutions
    Dr. Monika Schneider, American Association of Immunologists
    Dr. Michael Siegel, National Psoriasis Foundation
    Dr. Kentner Singleton, National Institute of Allergy and Infectious Diseases, NIH
    Ms. Kristin Stephenson, Muscular Dystrophy Association
    Dr. Hannah Valantine, Office of the Director, NIH


    A motion was made, seconded, and passed to accept with no changes the minutes of the 84th NAMSAC meeting, held on September 8, 2014.


    Future Council meetings are currently planned for the following dates:

    June 16, 2015
    September 8, 2015
    February 2, 2016
    June 7, 2016
    September 13, 2016


    Dr. Katz welcomed Council members, NIAMS staff, and guests and opened his Director's Report by introducing five ad hoc Council members:

    • Dr. Joan E. Bechtold is the Gustilo Professor of Orthopaedic Research at the University of Minnesota. Dr. Bechtold's research focuses on improving the bone-implant interface when patients undergo revision joint replacements. An NIH grantee since 1995, she gives back to the research community through service on various NIH study sections and active involvement in professional organizations such as the Orthopaedic Research Society, where she currently holds the position of Immediate Past President.
    • Dr. V. Michael Holers is the Scoville Professor of Rheumatology at the University of Colorado School of Medicine, where he is also head of the Division of Rheumatology. His laboratory conducts basic and translational research on the roles of complement receptors and membrane regulatory proteins in the immune response, with a special emphasis on B lymphocytes and autoimmune diseases. Dr. Holers is an integral part and leader of the newly initiated Accelerating Medicines Partnership (AMP) program. He is also a Consulting Editor for the Journal of Clinical Investigation and has contributed his expertise to several NIH study sections.
    • Dr. Sundeep Khosla is the Dr. Francis Chucker and Nathan Landow Research Professor, a Mayo Foundation Distinguished Investigator, and the Dean for Clinical and Translational Science at the Mayo Clinic College of Medicine in Rochester, MN. Dr. Khosla is the Principal Investigator (PI) of the Mayo Clinic's Center for Clinical and Translational Science and leads a research team that is investigating the mechanisms of bone loss in women and men, sex steroid action on bone, and the biology of osteoprogenitor and stem cells. He is also a Past President of the American Society for Bone and Mineral Research and a former member of the National Institute on Aging's Advisory Council.
    • Dr. Amy Paller is the Walter J. Hamlin Professor and Chair of the Department of Dermatology at Northwestern University's Feinberg School of Medicine. She is a former President of the Society for Investigative Dermatology and an active member of numerous other professional societies. As a pediatric dermatologist, Dr. Paller specializes in clinical research related to genetic and immune-mediated inflammatory conditions in children. She has led more than 70 clinical trials and is currently studying eczema, psoriasis, ichthyoses, and epidermolysis bullosa.
    • Mr. Richard F. Seiden joins the Council as a public representative. A member of the California Bar since 1973, he is a partner with Foley and Lardner, LLP, in Los Angeles. Mr. Seiden's experience includes serving as outside general counsel to major nonprofit hospital systems. In this role, he advised and assisted his clients as they developed integrated healthcare delivery systems that allowed them to treat patients in a managed care environment. Mr. Seiden is a former Chair of the Board of Trustees of the National Psoriasis Foundation.

    Update on Budget and Congressional Outreach Activities

    Dr. Katz reported that in FY 2014, the NIAMS funded 288 new and competing continuation research project grant (RPG) applications for a success rate of 18.1 percent—a figure higher than the FY 2013 rate of 15.9 percent, and equal to the overall NIH success rate for the year, which also was 18.1 percent.

    On December 16, 2014, the President signed the Consolidated and Further Continuing Appropriations Act of 2015, which funds most of the Federal government for the remainder of FY 2015. The NIAMS 2015 budget will be $521.7 million—a $1.6 million increase over its budget for FY 2014, but still about 2 percent lower than the Institute's FY 2012 budget. Dr. Katz reminded Council members that the Institute has posted its funding plan on the NIAMS website.

    On February 2, 2015, President Obama released his FY 2016 budget request to Congress. The amount requested for the NIH is $31.3 billion, which is an increase of approximately $1 billion over the FY 2015 budget. The amount for NIAMS is $533.2 million, which represents an increase of approximately $12 million (or just over 2 percent) above FY 2015. Dr. Katz reminded Council members that the President's budget is only one element of the NIAMS final budget.

    During his recent State of the Union Address, President Obama introduced a $215 million Precision Medicine Initiative that is included in his fiscal year (FY) 2016 budget. The NIH is leading the design and implementation of this effort, which is intended to transform the way diseases are prevented and treated. The NIH will receive approximately $130 million, with the majority (roughly $70 million) allocated to the National Cancer Institute.

    Dr. Katz explained that in addition to supporting research for the benefit of the public, a critical part of the NIH mission is to inform key stakeholders about the scientific advances, opportunities, and challenges that exist in biomedical and behavioral research. As such, it is essential that policymakers, including members of Congress and their staff, are aware of the progress and promise that NIAMS investments hold for the Nation's health. On October 15, 2014, the NIAMS and the NIAMS Coalition (an independent consortium of almost 90 professional and voluntary organizations that raises awareness about NIAMS-funded research) hosted a Congressional staff tour of some of the laboratories in the Institute's Intramural Research Program (IRP). During the tour, staffers learned about NIAMS intramural and extramural research, training for the next generation of scientists, and NIAMS outreach programs. This was the last Coalition event organized by Co-Chair Ms. Sarah D'Orsie; Mr. Simit Pandya of the American Academy of Orthopaedic Surgeons will be rotating into the position and serving a 2-year term as the new Coalition Co-Chair. He joins current Co-Chair Ms. Leah Howard of the National Psoriasis Foundation.

    Another event was sponsored by the Lupus Foundation of America and the Rheumatology Research Foundation. As co-sponsors of the Accelerating Medicines Partnership Network in Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE), the groups hosted a Congressional briefing.

    As a member of the Muscular Dystrophy Coordinating Committee (MDCC), which Congress established in 2001 with the passage of the MD-CARE Act, the NIAMS has been involved in updating the Action Plan for the Muscular Dystrophies. The NIH will be requesting public comments on the draft plan, which is available for review through a link on the NIAMS website. In addition, nominations are being sought for potential public representatives to the MDCC.

    Highlights of Selected Recent Scientific Advances

    • As part of the Spine Patient Outcomes Research Trial (SPORT), researchers led by Dr. Jim Weinstein from Dartmouth have compared surgical and non-surgical treatment for the three most common causes of severe low back pain. Although SPORT's data revealed that the benefits of surgery for disc herniation remain at up to 8 years, a new paper by the research team reports that differences between outcomes for the surgical and non-surgical treatments for spinal stenosis decrease with time (Spine. 2015 Jan 15;40(2):63-76. PMID: 25569524).
    • The Multicenter Orthopaedic Outcomes Network (MOON) has been following a cohort of patients who underwent anterior cruciate ligament (ACL) reconstruction surgery more than 10 years ago. Approximately 20 percent of the I ,400 people in the study had tom their ACL, injured the meniscus that cushions the knee joint, and had both injuries repaired during the same surgery. MOON investigators were interested in how long the meniscal repairs and their associated benefits last. The group, under the leadership of Dr. Kurt Spindler at the Cleveland Clinic, had hypothesized that meniscal repairs would deteriorate with time. Instead, their data showed that patients continue to benefit from meniscal repair surgery for up to at least 6 years. Only 14 percent of the participants needed a second operation because their initial meniscal repair "failed." This finding supports the value of meniscal repair over partial or complete removal—a treatment option that has increasingly become associated with the development of osteoarthritis (OA) (Am J Sports Med. 2014 Sep;42(9):2184-92. Epub 2014 Jul 14. PMID: 25023440).

      Council member Dr. Martha Murray, Associate Professor or Orthopaedic Surgery and Harvard Medical School, explained that the MOON study is following a cohort of mostly young athletes. This multicenter study is the largest study of ACL injuries and includes a population of study subjects anticipated to have high rates of knee OA. The MOON has found that girls under 20 years of age who go back to playing soccer have a 20-30 percent chance of tearing an ACL in the ensuing years. This type of information is useful when counseling patients and discussing what activities they choose to participate in following surgery. MOON has an 85-90 percent follow-up rate at 6 years, and some 10-year data are coming in.
    • The Osteoarthritis Initiative (OAI) is a multicenter, observational study of individuals with risk factors for early osteoarthritis (OA) who were followed over an 8-year period for the development and/or progression of knee OA. The data, specimens, and images collected under this NIH- and industry-funded public-private partnership are publically-available to investigators worldwide. A group led by Dr. Tim McAlindon at Tufts University used the clinical and imaging data from the OAI to discover that age and recent knee injury were highly associated with rapid development and progression of knee OA. Specifically, the risk of disease progression was highest during the first year after the injury-a finding that is consistent with what is known about OA in younger adults. This suggests that the period shortly after an injury would be an opportune time for therapeutic interventions if an effective one was available (Arthritis Care Res. 2014 Nov;66(11):1673-9. PMID: 24782446).
    • Hyaluronic acid (HA) is one of the major lubricating molecules found in synovial fluid. One approach to reducing OA pain is to lubricate the joint with direct injections of HA. Some injection studies have shown benefit, but others have not-reports that injected HAs quickly leave the joints and do not all go to the regions where lubrication is needed partially explain why the treatments work less well than expected. To increase HA retention and targeted binding in joints, Dr. Jennifer Elisseeff and her team at the Johns Hopkins University developed a peptide that could bind collagen in joint tissues on one end and HA on another. Experiments using rat knees showed that the peptide captured HA and retained it in the complex joint environment (Nat Mater. 2014 Oct;l3(10):988-95. Epub 2014 Aug 3. PMID: 25087069).
    • Science Translational Medicine recently published two papers from NIAMS-funded laboratories describing cell-based therapies against the disease epidermolysis bullosa (EB), a family of rare, inherited skin disorders that causes severe, painful blisters at even the slightest touch. Not all skin cells in all patients have the disease-causing mutation, however. When some skin cells spontaneously correct the mutation, the patients are said to display "revertant mosaicism."
      • Dr. Angela Christiano and her team at Columbia University took advantage of this phenomenon to develop a "natural gene therapy" approach that they tested in mice. Her group: (1) made induced pluripotent stem cells (iPSCs) from keratinocytes from a normal-looking patch of skin in a patient who had a generalized form of EB, (2) differentiated these spontaneously corrected cells into keratinocytes that express the normal form of the collagen protein, and (3) tested the resulting cells for their ability to form 3-dimensional skin equivalents in culture and to reconstitute human skin on the backs of immunocompromised mice. The results were promising—the epidermis in both systems appeared normal, and the cells expressed the corrected collagen protein as expected (Sci Trans/ Med. 2014 Nov 26;6(264):264ra164. PMID: 25429057).
      • A study by Dr. Tony Oro's group at Stanford University used an approach to correct the genetic defect that causes recessive dystrophic EB (RDEB). They generated iPSCs from keratinocytes and fibroblasts gathered from skin biopsies from three adult patients with RDEB. After correcting the disease-causing mutation using a new adena-associated viral approach and screening the cells to confirm that they did not have any genes associated with squamous cell carcinoma (a fatal cancer common to RDEB), the investigators allowed the stem cells to differentiate into keratinocytes that expressed full-length wild-type collagen VII protein in mice (Sci Trans/Med. 2014 Nov 26;6(264):264ra163. PMID: 25429056.) The results were similar to those from the Christiano laboratory: both in vitro and when implanted into mice, the corrected keratinocytes were able to form sheets of skin with-—in this case—normal collagen VII. Together, these studies make important progress toward the development of patient-specific cell-based therapies for EB and for other rare heritable diseases of skin, and for personalized iPSC-derived medicine in general.
    • In complementary publications in Nature Medicine, Dr. Rudnicki from the University of Ottawa (and a NIAMS grantee) and Dr. Sacco from the Sanford-Burnham Medical Research Institute describe the role of JAK-STAT signaling during muscle regeneration. The papers suggest that in aging and in the dystrophies, chronic inflammation activates JAK-STAT signals in an unregulated manner. This leads to deficient regeneration of damaged tissue, and may ultimately lead to a complete depletion of the satellite cell pool. On the other hand, mouse and cell culture data suggest that therapeutic manipulation of the JAK-STAT pathway may be a way to treat muscle wasting and disease (Nat Med. 2014 Oct;20(10):1182-6. doi: 10.1038/nm.3656. Epub 2014 Sep 7. PMID: 25194572) (Nat Med. 2014 Oct;20(10):1174-81. Epub 2014 Sep 7. Erratum in: Nat Med. 2014 Oct;(10):1217. PMID: 25194569).
    • Autoinflammatory diseases such as chronic recurrent multifocal osteomyelitis (CRMO) differ from autoimmune diseases in that the immune system does not attack a defined target, but instead causes indiscriminate inflammation and tissue damage. Work by Dr. Thirumala­ Devi Kanneganti and colleagues from St. Jude Children's Research Hospital further supports the growing body of evidence that diet can affect the bacteria within the intestinal tract and intestinal flora can greatly influence disease. Replacing the normal low-fat diet of mice that spontaneously developed autoinflammatory osteomyelitis with a high-fat diet protected the animals from the inflammatory bone disease. The two diets had dramatic effects on which bacteria lived in the animals' guts, and treating low-fat-fed mice with broad-spectrum antibiotics significantly protected the mice from developing osteomyelitis. Additionally, giving the low-fat-diet mice doses of bacteria isolated from the guts of the high-fat-diet mice also protected the susceptible animals from developing the disease (Nature. 2014;516(7530):246-9. Epub Sept. 28. PMID: 25274309.)
    • Autoinflammatory diseases such as chronic recurrent multifocal osteomyelitis (CRMO) differ from autoimmune diseases in that the immune system does not attack a defined target, but instead causes indiscriminate inflammation and tissue damage. Work by Dr. Thirumala­ Devi Kanneganti and colleagues from St. Jude Children's Research Hospital further supports the growing body of evidence that diet can affect the bacteria within the intestinal tract and intestinal flora can greatly influence disease. Replacing the normal low-fat diet of mice that spontaneously developed autoinflammatory osteomyelitis with a high-fat diet protected the animals from the inflammatory bone disease. The two diets had dramatic effects on which bacteria lived in the animals' guts, and treating low-fat-fed mice with broad-spectrum antibiotics significantly protected the mice from developing osteomyelitis. Additionally, giving the low-fat-diet mice doses of bacteria isolated from the guts of the high-fat-diet mice also protected the susceptible animals from developing the disease (Nature. 2014;516(7530):246-9. Epub Sept. 28. PMID: 25274309.)

    Personnel Changes at the NIH/NIAMS

    At the NIH

    • After more than 30 years as Director of the National Library of Medicine, Dr. Donald A.B. Lindberg will be retiring from the NIH in March.

    At the NIAMS

    • Dr. William Sharrock is retiring from the Federal government after 23 years of service. Throughout his career, Dr. Sharrock's scientific attention has focused chiefly on the cellular and molecular mechanisms of bone development and metabolism-phenomena that are relevant both to osteoporosis as well as the rare skeletal diseases, many of which are genetic in origin. In recent years, he has taken a leadership role in several aspects of the adoption of genetic/genomic approaches by NIAMS-supported scientists. Dr. Katz expressed gratitude for his outstanding efforts in this area, as well as his mentorship to NIAMS staff and the research community. Dr. Sharrock has agreed to work with the NIAMS on a part-time basis as a consultant.
    • Dr. Lee Alekel has joined the NIAMS as a Program Director in the Division of Musculoskeletal Diseases. Dr. Alekel comes to the NIAMS from the newly renamed National Center for Complementary and Integrative Health (NCClli) where she served for almost 4 years as a Program Director managing a broad portfolio of grants including women's health and aging.
    • Ms. Jennifer Chi has joined the Division of Skin and Rheumatic Diseases as a contractor who will be the Clinical Operations Manager for the AMP Network in RA and Lupus.

    Update on Activities and Plans

    Dr. Katz noted that the National Center for Complementary and Alternative Medicine (NCCAM) has had its name changed to the National Center for Complementary and Integrative Health (NCCIH). The new name reflects the Center's research commitment to studying promising health approaches that are already being used by the American public.

    Dr. Katz then provided updates on two NIH-wide policy changes that are expected to further improve the ability of investigators to conduct clinical research and to apply their findings to future studies. As presented at the Council's September 2014 meeting by Dr. Kathy Hudson, NIH Deputy Director for Science, Outreach, and Policy, a new policy will increase the use of single Institutional Review Boards (IRB) for multi-site, NIH-funded studies. The goal is to enhance and streamline the process of IRB review and reduce inefficiencies so that research can proceed efficiently without compromising ethical principles and protections. The NIH is also moving forward on plans to promote the dissemination of clinical trials results. This process is occurring in parallel with a departmental effort to clarify clinical researchers' requirements under the Food and Drug Administration Amendments Act of 2007.

    During the September 2014 Council meeting, the Institute presented plans for a new program that will provide additional funding stability and flexibility for scientists who have recently received their first competitive renewal, or type 2, RPG. The goal of the program, Supplements to Advance Research (STAR), is to enable "early established" investigators to build a robust and innovative research program. The NIAMS is also reaching out to clinical and patient-oriented investigators who are still receiving formal mentoring as part of their career development.

    The NIH has decided to close the National Children's Study (NCS) following the recommendations of a working group of the Advisory Committee to the NIH Director (ACD). The ACD working group recommended that, while the overall goals of the NCS should remain a priority for future scientific support, the NCS was not feasible as currently outlined. Various proposals are being considered from across the NIH; one entails expanding the Patient Reported Outcomes Measurement Information System (PROMIS) by validating measures for children that include environmental components. If approved, the program will leverage existing pediatric banks for chronic conditions such as juvenile arthritis, asthma, and obesity.

    Another ACD activity focuses on the NIH IRP. During the June 2014 NAMSAC meeting, Dr. Koretzky provided an update on NIAMS activities related to the Long-Term Intramural Research Program Report. Since then, the ACD's working group has completed its analysis and presented its report at the December Advisory Committee meeting. The working group acknowledged that budget constraints hamper NIH's ability to fully implement the numerous recommendations in the report. As a next step, several members of NIH leadership (including Dr. Katz) are discussing an initial response to the report that will be shared with all IC Directors. Dr. Katz's ShortTakes Director's Column this month features the NIAMS IRP.

    In recognition of Hispanic Heritage Month in September, NIAMS hosted its first ever Twitter chat in English and Spanish. The chat focused on lupus, a disease that disproportionately affects Hispanic women. Tweets were posted in both languages, and questions were answered in the language in which they were received. During the chat, Drs. Mariana Kaplan (Chief of the NIAMS Systemic Autoimmunity Branch) and Susana Serrate-Sztein (Director of the NIAMS Division of Skin and Rheumatic Diseases) shared the latest advances in lupus research. Dr. Irene Blanco, Assistant Professor of Rheumatology at Albert Einstein College of Medicine of Yeshiva University also participated and assisted in responding to questions. Other ICs and HHS offices, including the HHS Office on Women's Health, also participated. The hour-long chat generated almost 600 tweets from more than 100 contributors. This bilingual Twitter chat was part of NlAMS's ongoing efforts to reach multicultural communities with health information and resources.

    A key component of NIAMS' National Multicultural Outreach Initiative is the development and distribution of annual health planners and an electronic toolkit of health information. The materials are designed to increase awareness among adults with conditions of the bones, joints, muscles, and skin about the availability of resources from the NIH and other Federal agencies. The National Multicultural Outreach Initiative's bilingual Spanish health planner recently received a Gold Award-the highest honor-from the National Health Information Awards Program. Dr. Katz congratulated the NIAMS team as well as NIAMS Coalition representatives and Council member Dr. Gwendolyn Powell Todd—a patient, health advocate, and educator who has strongly supported the Institute's efforts to ensure that NIAMS resources are available to all communities.

    Dr. Katz concluded his Director's Report by introducing a discussion on NIAMS' proposed Core Centers for Clinical Research program. Two years ago, the Institute undertook a formal evaluation of its Centers program-specifically, the NIAMS Research Core Centers, Centers of Research Translation (CORTs), and Multidisciplinary Clinical Research Centers (MCRCs). Dr. Katz thanked Council members Dr. Mike Holers and Dr. Christy Sandberg (Professor of Pediatrics at Stanford University) for serving on the NIAMS Centers Evaluation Working Group, as well as those who participated in the listening sessions held with the Institute's various communities. The NIAMS recently reissued its suite of funding announcements for the Research Core Centers, which it supports using the P30 mechanism. Webinars for prospective applicants will be held in late February or early March. As the Institute moves forward with its other programs, Dr. Katz expressed particular interest in hearing from Council members regarding the methodology cores that are currently part of the P60 MCRC program. These Centers have been in existence at the Institute for roughly 12 years.

    The NIAMS Centers Evaluation Working Group has observed that Methodology Cores continue to play an important role in fostering clinical research and collaboration, but noted that there may be some benefit to disconnecting them from the individual research project components of the awards. Working group members also strongly encouraged the NIAMS to preserve investigators' flexibility in the design of Centers, and, as a consequence, to focus particularly on the methodology cores rather than combining them with the clinical studies. Within this context, the NIAMS is re-examining how to support what it is now calling the Core Centers for Clinical Research (CCCRs). The Institute will be soliciting input from the community and is viewing the CCCRs from the perspective of meeting its communities' multidisciplinary clinical research needs. Dr. Katz noted that the methodology cores are embedded in many of the Clinical and Translational Science Awards (CTSAs) and that there is also a larger, trans-NIH effort to improve Cores' efficiencies and eliminate programmatic redundancies.


    Dr. Holers noted that as the NIAMS Centers Evaluation Working Group was reviewing the centers program, the group had a strong sense that the Institute would be well-served by moving away from a "one-size-fits-all" structure to one that would be more flexible. The Working Group felt it was necessary that different groups be able to come together in a team-based approach, and that flexibility is necessary to accomplish this. He commented that this appears to be the direction in which the NIAMS is moving. Dr. Carter noted that one of the clear tenets outlined in the Institute's Centers Evaluation Working Group Report is that centers are an opportunity to foster team-based research focused on understanding human disease. How the methodology cores will progress moving forward is less clear; they are valuable and should be preserved, but their future structure is uncertain.

    Dr. Khosla expressed support for NIAMS' work in this area, suggesting that it will address two currently existing gaps that have arisen as a result of dramatic shifts in the CTSA program: (1) supporting pilot and feasibility studies in clinical research (as there is a greater emphasis within the CTSA program of supporting pilot and feasibility studies in areas of translational science), and (2) providing infrastructure support (as this type of support is diminishing from other sources) for methodology development and other types of supporting activities.

    Council member Dr. Sherine Gabriel, Dean of the Mayo Medical School, commented that this is an important direction in which the Institute should move, and suggested that the NIAMS intersect with the methodology activities ongoing at the Patient-Centered Outcomes Research Institute (PCORI). Dr. Serrate-Sztein suggested that the CCCRs could establish partnerships with patient advocacy organizations and other groups that advise PCORI and/or participate in PCORI-sponsored studies. She also noted that in seeki ng feedback on its centers program from the community, the NIAMS will receive feedback on how to take advantage of existing resources approaches for integrating with the CTSAs, and whether it would be advisable to help focus the CCCRs. Dr. Khosla commented that one of the most obvious intersections with PCORI is through the National Patient-Centered Clinical Research Network (PCORnet). He explained that PCORnet may be particularly usefu l for late-stage translation, comparative effectiveness, and other types of work.

    Dr. Katz concluded this discussion session by asking Council members to consider providing comments to any Requests for Information (RFis) that the Institute may issue regarding its centers program.


    Dr. Hannah Valantine, NIH 's first Chief Officer for Scientific Workforce Diversity, opened her remarks by emphasizing that diversity is essential for good science. An ACD working group tasked with examining the state of NIH's scientific workforce made 13 recommendations and highlighted the importance of diversity relative to: (1) excellence, creativity, and innovation; (2) broadening the scope of inquiry and finding solutions to complex problems of health and disease; (3) narrowing the health gap; and (4) ensuring fairness. She explained that at present, 33 percent of college-aged students are from underrepresented groups; however, that percentage drops significantly along the scientific pathway such that only 6 to 7 percent of faculty at most leading academic institutions are from underrepresented groups. Efforts are needed to continue bolstering the pipeline to ensure that students from diverse backgrounds have the ability to advance through career paths that will ultimately allow them to reach the independent investigator or similar biomedical research scientist career level. Dr. Valantine reminded the group that when people do not see others like themselves along the career path, they are more likely to give up.

    The 13 ACD working group recommendations were used as a foundation in developing the NIH Transformative Di versity Initiative, which has: (1) created Dr. Valantine's position, Chief Officer for Scientific Workforce Diversity, (COSWD); (2) established three integrated programs (Building Infrastructure Leading to Diversity [BUILD], the National Research Mentoring Network [NRMN], and a Coordination and Evaluation Center [CEC]); and (3) promoted activities to ensure fairness in the peer-review process.

    In creating the COSWD position, the ACD working group sought to recruit an active biomedical researcher with a commitment to diversity and strong credibility in the academic community. The position's primary responsibility is to coordinate diversity programs across the NIH that are subject to rigorous evaluation. The overall mission of the COSWD is to build a diverse, trans­ NIH scientific workforce that is a model for recruiting the most talented scientists into biomedical research. The COSWD is using the IRP to pilot interventions to diversify the workforce. Dr. Valantine's strategy for expanding diversity in the IRP is focused on tenure, tenure track, staff clinicians, staff scientists, and postdoctoral students. Her office is concentrating on cluster hires and targeted recruitments, identifying resources for hiring the most talented candidates, and establishing a program to create a climate of belonging (e.g., through professional development, mentoring/sponsorship, etc.).

    Her office's flagship program for the extramural community, Enhancing the Diversity of the NIH-Funded Workforce, made its first series of awards in October 2014. The program aims to transform the way all biomedical researchers are trained, using social science research to enhance biomedical research training. The program's goal is to develop and test new approaches to training and mentoring on a large scale. Students from underrepresented backgrounds will be the primary beneficiaries, but all students will ultimately benefit, resulting in a stronger biomedical research enterprise. The program is based on eligibility criteria for applicants; in order for an institution to apply for one of these awards, they had to be receiving no more than $7.5 million in NIH funding and had to have at least 25 percent of their students receiving Pell Grants. Applicant institutions also had to partner with a research-intensive institution so that they could provide the critical research experience necessary for developing students in biomedical research. The Enhancing the Diversity of the NIH-Funded Workforce program features three major integrated initiatives:

    • BUILD — This initiative is a set of experimental training awards focused on attracting and retaining students from diverse backgrounds into the biomedical research workforce.
    • NRMN — The NMRN represents a nationwide network of mentors from a variety of disciplines that defines best practices for mentoring at all career stages, provides training for mentors, and establishes a network and professional development for mentees.
    • CEC — The CEC rigorously evaluates the BUILD and NRMN initiatives to determine what works and for whom. It is responsible for the dissemination of successful training and mentoring strategies.

    Dr. Valantine emphasized that these initiatives differ from other, previous NIH-funded diversity programs in three key ways. First, these initiatives are organized around a consortium concept (i.e., awardees work together as a consortium in partnership with the NIH), and each award has a project officer who is a representative from the NIH. Second, there is a heavy emphasis on evaluation, with evaluation carried out in real time and with multiple metrics to assess impact. The CEC will work with sites to develop tailored assessment plans. Third, there is a strong dissemination component, such that lessons learned will be broadly shared. To date, ten BUILD sites have been awarded. Total funding for the Enhancing Diversity in the NIH-Funded Workforce program is $31.3 million per year over the next 5 years.

    Dr. Valantine then discussed the national strategy to enhancing scientific workforce diversity, with a focus on a coordinated approach to intervening on barriers to transition across the biomedical career path. In concert with NIH leadership, Dr. Valantine's office is working to develop a national comprehensive plan that promotes innovation in scientific workforce diversity (she noted that innovation is an essential part of the research culture). As the NIH leads and catalyzes scientific workforce diversity through data-driven innovations to recruit and retain the most talented scientists, it is seeking to achieve sustainable transformation in scientific workforce diversity by creating seamless transitions across biomedical research career paths. In establishing "Hubs of Innovation," the NIH plans to create networks and strong infrastructure that support career development pathways enabling scientists, including those from underrepresented groups, to transition seamlessly across research career paths. Essential components of this national strategy include: (1) strategic partnerships (with research-intensive institutions and organizations focused on education/training), (2) implementation and scaling (using a systems approach), (3) tracking and evaluation, and (4) organizational commitment.

    Dr. Valantine concluded her remarks by summarizi ng the three primary strategic directions in which the COSWD is moving:

    • The Enhancing the Diversity of the NIH-Funded Workforce program (including BUILD, NRMN, and CEC).
    • Using the NIH IRP as a "laboratory" for testing i nterventions to diversify the biomed ical workforce.
    • Establishing national "Hubs of Innovation" as part of the national strategy to enhance scientific workforce diversity.


    Dr. Koretzky commented that the vision and efforts of the COSWD are extraordinary and critical. He noted that most academic medical centers have established diversity programs in place that may or not be well known to the NIH (primarily because they are funded with local resources). He suggested that bringing together NIH Program Directors with leadership of these programs (e.g., to develop common metrics and tracki ng methods) could help advance and expand the cause of the COSWD and the NIH overall. Dr. Valantine agreed, noting that one of the first steps in developing the concept of national "Hubs of Innovation" to enhance scientific workforce diversity involved a webinar for Deans of academic medical centers to solicit their input. The next stage of this work will involve meeting with leaders f rom these institutions to avoid duplicati ve efforts and leverage existing resources. Dr. Gabriel expressed support for this type of activity.

    Council member Mr. Alexander Silver, Chairman of the Jackson Gabriel Silver Foundation, noted that the long-term changes envisioned by Dr. Valantine and her office must reach back to early ed ucation to address biases that become entrenched at a young age. He asked abou t NIH's plans in this regard. Dr. Valantine pointed out that some of the interventions for certai n social and psychological issues work rapidly, are very inexpensi ve, and can have dramatic results. However, these interventions are not well studied to date and require further work. She also noted that rapid change may best be seen in faculty hiring, which has a direct impact on the persistence of trainees. Dr. Valantine is currently working as a Co-Chair of a committee that i s bringing Federal agencies together to address broadening participation in science, technology, engineering, and math (STEM) programs among underrepresented populations.

    Dr. Sandborg expressed support for COSWD efforts to balance the issues around stereotypes and what underrepresented minorities and women can do to improve their sense of belonging through creating role models and rapid interventions that have far-reaching effects. She also pointed to the need to address (and recognize) unconscious bias. Dr. Valantine agreed, noting that even in the private sector, companies such as Intel are investing in ways to expand workforce diversity and address the problems related to unconscious bias.

    Dr. Khosla asked how Dr. Valantine's office defines success, noting that there are currently more individuals who have Ph.D. degrees than there are jobs available to them. Dr. Valantine noted that work on scientific workforce diversity issues falls in the context of these types of broader workforce questions. An ACD committee is considering these challenges and is identifying areas that require additional work.


    Ms. Shahnaz Khan, Clinical Coordinator in the Division of Extramural Research Activities, provided an overview on the NIH Policy on Inclusion of Women and Minorities in Clinical Research, noting that Council members were provided with NIH's FY 2013-2014 report. In 1993, the NIH was mandated by Congress (through the NIH Revitalization Act) to establish guidelines for the inclusion of women and minorities in clinical research. The NIH revised its inclusion policy in 1994, and in 2000, the General Accounting Office issued a report with recommendations to the NIH Director. As a result of this report, the NIH amended its policy in 2001 with major updates in four areas: (1) definition of clinical research, (2) racial and ethnic categories, (3) clarification of NIH-defined Phase III clinical trials, and (4) roles and responsibilities of NIH staff and the extramural community. Since that time, the NIH has not changed its policy, but it has enhanced its business processes for the collection and reporting of data.

    Every 2 years, Council members review aggregate IC data and may ask questions. The written report, which is shared with Council members, includes a description of the Institute's efforts to comply with the law and NIH policies, as well as the number of women and minorities that were enrolled in clinical research during the past 2 years. Ms. Khan indicated that overall, the total number of enrolled participants has remained consistent since the last 2-year reporting period. There have been some slight decreases in Asian and African American participation, largely due to the fact that some studies have completed enrollment and are no longer reporting during the defined period. She emphasized that the goal of the inclusion policy is to monitor the trends in recruitment of women and minorities rather than to focus on changes in the actual numbers. This year's report is consistent with previous reports in showing that overall, the NIAMS is funding clinical research that includes women and all minority groups in an appropriate manner based on the diseases and populations that fall within its mission.

    Dr. Katz asked about reporting data on the inclusion of children, other minority groups, the gay/lesbianlbisexual/transgender community, those living in urban/rural areas, etc. Ms. Khan indicated that the collection of data on these groups is a significant challenge. In general, the reporting systems are slow to catch up and are significantly constrained by the funds available to do this work. Although the NIH does not yet have the electronic means to collect much of this data and incorporate it into its existing systems, there is significant interest on the part of many IC Directors in doing so.

    Dr. Powell Todd asked about the steps taken to ensure the inclusion of women and minorities during the peer review process. Ms. Khan explained that although there are no set criteria for reviewers, if a minority group or gender is being excluded from a proposed study, a scientific justification must be proposed in the application. Dr. Katz added that efforts to ensure the inclusion of women and minorities do not end at the peer review stage. NIAMS Program Directors pay careful attention to this issue and play a critical role in assessing the inclusion of women and minorities in Institute-funded projects.

    Dr. Holers asked if the shift to using more electronic health records and de-identified samples in clinical settings will necessitate a change in NIH's policy. Ms. Khan explained that if an applicant plans to use de-identified samples that have no associated gender or ethnicity data, the policy does not apply.


    Ms. Anita Linde, Director of the Office of Science Policy, Planning and Communications, NIAMS, provided an overview of "The Future Directions of Lupus Research" plan, which is being led by the Institute on behalf of the NIH. In 2007, a House Appropriations Committee report requested that the NIH develop a lupus plan that articulates opportunities and challenges. The plan was prepared with extensive input from scientific experts from the lupus research community. The broad goals and priorities included in the 2007 plan included:

    • Laying the foundation for lupus prevention
    • Identifying triggers of disease
    • Defining target organ damage mechanisms
    • Understanding autoantibodies
    • Expanding biopsychosocial research
    • Discovering and validating biomarkers
    • Moving forward treatment and therapy
    • Resources and infrastructure

    Last summer, the NIH received a formal request from the Congressional Lupus Caucus to review the 2007 plan, evaluate progress against the broad research goals and priorities, and develop a coordinated action plan for lupus research going forward. This request indicated that those on Capitol Hill were interested in learning more about the pace of lupus research as well as its scope. As the convener of the Lupus Federal Working Group, the NIAMS is responding in two ways: (1) an evaluation report highlighting the progress towards achieving the broad goals and priorities included in the 2007 plan, and (2) an action plan that updates the goals and priorities described in the 2007 plan to reflect new scientific opportunities and challenges.

    Ms. Linde explained that an RFI has been issued to obtain external input and many NIH ICs have been asked to provide input as well. The current RFI asks for input on the following: (1) the most significant advances/publications since 2007, (2) the most important scientific opportunities in lupus research, (3) areas that are ready for progress in the short term, (4) gaps to be addressed to advance lupus research, and (5) topics to add or remove from the broad goals and priorities highlighted in the 2007 plan so that the current state of the science is reflected. The closing date for this RFI is February 13, 2015. In the spring of 2015, these comments will be reviewed and the evaluation report and action plan will be developed. A webinar will be held with the scientific community to obtain input on the draft action plan (scheduled for May 27, 2015). An update will be given to Council members at the June 16, 2015 NAMSAC meeting. In the summer of 2015, the action plan will be revised and a second RFI will be issued to obtain comments on the draft action plan. The final plan will be presented to the Congressional Lupus Caucus in the fall of 2015 (regular updates are being given to the Congressional Lupus Caucus, the NAMSAC, and the Lupus Federal Working Group).


    Dr. Powell Todd asked if the new plan would include information on the economic impacts associated with lupus. Ms. Linde noted that the report will include information on health disparities related to lupus. Dr. Powell Todd explained that some lupus patients often have to make the choice of not getting treatment because of economic difficulties or other reasons. Ms. Linde indicated that these issues likely fall outside the scope of the NIH plan and added that there is an ongoing, parallel effort at the Centers for Disease Control and Prevention focused on public health issues related to lupus that may be a more appropriate place for a discussion of these issues.

    Dr. Koretzky asked about the RFI process and whether those who submit comments and questions can see all of the comments and questions that were submitted (as well as NIH's responses). Ms. Linde explained that the RFI is not intended to serve as a virtual conversation, and the full scope of all input received is not being widely disseminated. However, the input is being carefully reviewed and integrated within the context of the broad areas and priorities. When the new plan is made available for comment, there will be an opportunity for interested parties to collectively review the common themes that arose. Dr. Koretzky suggested that for future RFis, it would be useful to see a summary of the comments that were submitted. Ms. Linde noted that the May webinar will include a discussion on input received in response to the RFI.


    Dr. Carter provided Council members with an update on activities related to the AMP in RA and Lupus, reminding the group that it was briefed on this topic during the last NAMSAC meeting. Each center contributes resources and expertise that complements the others. The AMP RA/Lupus Network is led by a Leadership Center (under a distributed leadership model with experts from Stanford University and the University of Colorado) and includes lupus sites, RA sites, an analytics site that bridges both lupus and RA, a tissue research group, and a systems biology group. The Leadership Center is overseeing three primary activities thus far:

    • Tissue Research Group — The AMP Coalition Tissue Acquisition Research Network is providing the infrastructure and quality control for optimal sample tracking and interim storage.
    • Systems Biology and Data Management — Experts in this area are defining roles in the update of data, choosing appropriate analyses, and sample and data quality control for a standardized and harmonized approach across investigators and sites. This group is also responsible for the data-driven selection of SOPs.
    • Leadership Center Research, Coordination, Management, and Statistics Program — This program is supporting processes and procedures of the research sites to ensure collaboration, optimization, and establishment of a sustainable research network.

    The AMP RA/Lupus Network is currently in Research Phase 0, which involves developing standardized methods and standard operating procedures to identify which processes lead to the best data. While the Network waits for consent forms to be approved by IRBs so that data and tissue can be shared across sites, they are now: (1) utilizing existing protocols for tissue acquisition, processing, and biobanking; (2) comparing methods and ex periences between groups; and (3) developing clinical phenotyping and definitions for patient classification. The sites have all agreed to incorporate common language for data/tissue sharing into site protocols and consent forms. A draft plan for Phase 0 has been developed by the Network Leadership Committee, and a Joint Investigator/Steering Committee face-to-face meeting is planned for early June. Additional activities include identifying ways to preserve the data beyond the 5-year lifespan of this project and considering ways that the data from this project can be integrated or at least accessed through a common portal with data from the other two AMP projects (in Alzheimer's disease and type 2 diabetes). Once this step is complete, Research Phase I will focus on the disease-specific expression profile of tissue cells. Research Phase II will then address patient stratification. Funds for these activities were released late September 2014, and the first AMP RA/Lupus Network face-to-face meeting was held in October.

    Dr. Holers, who is a co-leader of the AMP RA/Lupus Network Leadership Center, commented that investigators view this initiative as both a challenge and an opportunity. Challenges lie in the complex nature of the work and difficulties associated with securing funding. However, these challenges have helped change the culture from an ROl-driven, individual laboratory-based approach to one that is integrative, sharing, and enables the synergistic work of the best scientists in clinical research, translational research, technology, as well as international collaborators.


    Dr. Serrate-Sztein commented that it may be interesting at some point in the future to try to extract some of the lessons learned from this endeavor, particularly in light of the increased emphasis on supporting team-based science and team-based approaches to solving critical questions relevant to the NIAMS mission. It may be that lessons learned from this initiative could be used to help develop future approaches and funding mechanisms. Dr. Katz emphasized that the AMP is a different approach to science and to moving the fields of RA and lupus forward, and it is hoped to result in significant contributions to knowledge regarding target tissues.

    Dr. Paller asked if skin is being included as a target tissue in the RA/Lupus AMP. Dr. Carter noted that one site is being included in the Network because it is examining uninvolved skin and had data indicating abnormalities and endothelial differences in uninvolved skin in lupus. Skin has long-been considered the second tissue to be analyzed in lupus, but there has been a concern that the skin tissue disease is very heterogeneous. Examining uninvolved skin may address this concern. Dr. Paller pointed to the need to ensure that experts in dermatology are involved in these types of efforts.


    Dr. Joan McGowan, Director of the Division of Musculoskeletal Diseases, updated Council members on two recent NIAMS roundtable discussions, one on developing 3-dimensional human tissue models to study musculoskeletal and skin physiology and pathophysiology, and one on the role of disc degeneration in neck and back pain. She reminded the group that the roundtable meetings are an integral part of the NIAMS planning process; a roundtable discussion on scleroderma is planned for the end of this month.

    Developing 3-Dimensional Human Tissue Models to Study Musculoskeletal and Skin Physiology and Pathophysiology

    Currently, most tissue culture research is done using 2-dimensional cultures, which carries with it significant limitations. A great value to the state of the science would be to incorporate human cells, organs, and/or tissues in a model that replicates more closely the in vivo situation. This roundtable featured discussions on how the NIAMS can move forward to take advantage of advances in the use of 3-dimensional tissue culture. Dr. McGowan presented a slide to demonstrate the complexity associated with 3-dimensional tissue models.

    Dr. McGowan identified the following short-term activities that were discussed during the roundtable: (1) encourage the development of functional musculoskeletal tissue models with multiple cell types, and add complexity to the existing skin models; (2) develop disease-specific models in NIAMS mission areas; (3) develop models to study the role of inflammation in NIAMS mission areas; and (4) explore tools and methodology to make iPSC-derived cells mature faster in in vitro cultures for the creation of musculoskeletal and skin 3-dimensional tissues. Dr. Paller noted that at her institution's skin disease research center, there is a strong focus on developing skin tissue engineering and 3-dimensional models. She stressed the importance of moving beyond just the keratinocytes and incorporating other cells. Having a common medium, the ability to develop multi-cell models that simulate skin, and the ability to utilize iPSC cells from patients that can be put into culture will advance the field significantly.

    The Role of Disc Degeneration in Neck and Back Pain

    Dr. McGowan reminded the group that neck and back pain is a significant public health problem in the United States. Low back pain and neck pain are the first and fourth leading causes, respectively, of years lived with disability. In 2005, costs associated with spinal pain in the United States totaled $86 billion. Many of the common causes of neck and back pain involve instability or degeneration of the intervertebral disc. Prevention or early identification could potentially halt the progression to chronic pain. Despite the large burden of disease, there are very few projects devoted to intervertebral disc research.

    Key questions guiding this roundtable discussion included: (1) What are the greatest scientific challenges related to understanding pathological changes leading to disc degeneration? (2) How will overcoming these challenges contribute to the identification of potential thera peutic targets? (3) What new knowledge is needed to develop in vivo and in vitro models for studies of the links between disc degeneration and OA of the spine and their connection to the development of pain? The scientific needs and opportunities that were identified during this roundtable discussion included the following:

    • Better understand normal disc development on a molecular level.
    • Identify the gene and/or protein signatures for earl y disc degeneration.
    • Better understand disc metabolism (i.e., how the disc thrives in an hypoxic environment) and the implications for strategies to prevent/treat disc degeneration.
    • Identify biomarkers at different stages, with a focus on molecular and cellular markers.
    • Better understand the role of inflammation in disc degeneration.
    • Develop/validate predictive markers of chronic spinal pain.
    • Better understand the mechanical components of neck and back pain, possibly using dynamic imaging tools.
    • Develop well-phenotyped human tissue samples to serve as "virtual biopsies."
    • Collect longitudinal data on neck and back patients and combine these data with biomarkers to identify those at high risk of developing neck and back pain.
    • Use "adjacent segment disease" (disc degeneration on both ends of a spinal fusion) as a model to study early disc degeneration.


    Dr. Khosla commented that with regard to the use of immune cells in 3-dimensional systems, the hematopoietic system is broader and that the definition of skeletal stem cells includes the ability to form bone and support hematopoiesis. He also noted that the roundtable discussion on 3- dimensional human tissue models included hematopoietic stem cell experts and asked if there are opportunities to partner with the National Heart, Lung, and Blood Institute (NHLBI) because the bone cells appear to be pathogenic in terms of leukemias and there appear to be significant opportunities for collaboration between bone and hematopoietic experts. Dr. McGowan agreed, noting that the tissue engineering/regenerative medicine/rnicrophysiologic systems represent a very trans-NIH area. Dr. Fei Wang, Program Director in the NIAMS Division of Musculoskeletal Diseases, noted that the NIAMS is consistently engaging the NHLBI on this topic.


    Dr. Mancini provided an update on the NIAMS 3rd Annual Forum for Clinical Mentored K Awardees. The purpose of NIH K08 (Mentored Clinical Scientist Development Research) and K23 (Mentored Patient-Oriented Research) Career Development Awards is to provide support for a sustained period of "protected time"" (3-5 years) for intensive research career development under the guidance of an experienced mentor or sponsor in the biomedical, behavioral, or clinical sciences leading to research independence. The Forum is held on an annual basis to discuss the challenges junior clinician-scientist investigators face in pursuing research independence, provide a forum for them to network with one another and interact with NIAMS extramural staff and leadership, and enhance the Institute's support of early stage clinician-scientists.

    The 3rd Annual Forum for Clinical Mentored K Awardees was held December 4-5, 2014. Participants included third-year K08 and K23 awardees, recent clinical mentored K award recipients who now have independent research careers, established investigators/mentors, and representatives from professional/voluntary organizations. Prior to attending the Forum, participants were asked to provide feedback regarding:

    • Obstacles facing clinician-scientists
    • Challenges associated with accessing NIH or university research resources
    • What the NIAMS, as well as the broader medical/scientific community, might do to help to support progression to independent clinician-scientists
    • What the NIAMS, as well as the broader scientific community, can do to encourage leveraging opportunities with industry and other Federal partners

    Key themes and messages that arose during discussions included:

    • K awardees would benefit from informational session(s) early in their award to discuss policy, other award options, etc. Dr. Mancini noted that last February, the NIAMS held its first webinar for newly awarded K08 and K23 awardees; the next webinar is scheduled for March 10, 2015.
    • The Forum highlighted the importance and roles of mentors as well as the value of a mentoring team approach/multi-disciplinary mentoring team.
    • Funding/salary support is a challenge (e.g., the gap between K award "capped" salary and actual salary). Tapping into additional resources and access to support staff is critical.
    • Organizations committed to supporting research career development should consider a type of K award supplement and/or bridge funding (some foundations are instituting these).
    • Increased interactions among the NIAMS, K awardees, and mentors may provide needed encouragement and impetus.


    Dr. Bechtold commented on the importance of these types of meetings and, more broadly, of helping to keep clinician-scientists moving forward. With regard to study sections, she suggested trying to get the clinicians on these study sections to serve in an advisory role. She also suggested that the team approach focus on proactively trying to pair basic scientists with clinicians. Dr. McGowan indicated that the interactions between all of the different fields, advocacy groups, and scientific organizations represented at the Forum spurred some of them to consider providing supplements or other types of funding to this target group of individuals. Dr. Katz commented that the Institute needs to give careful consideration to salary support for its K awardees, which are at the lowest end across the NIH.

    Before moving forward with the agenda, Dr. Katz noted that the STAR Program Funding Opportunity Announcement has been published and congratulated those Council members and NIAMS staff who contributed to its development.


    NIAMS Clinical Director Dr. Richard Siegel provided Council members with an update on the NIAMS IRP. The IRP represents roughly 10 percent of the NIAMS budget and includes approximately 250 staff, 23 faculty members, 20 clinical faculty members, the NIAMS Clinical Program (which features Rheumatology Fellowship training, advanced training, a disease­ focused Clinical Research Program, and community outreach), and the NIAMS Office of Science and Technology. All NIAMS IRP programs and Pis are reviewed every 4 years by the Board of Scientific Counselors.

    He began a discussion on scientific highlights of the IRP by noting that much of the IRP science has come about as a result of the Institute's 2007-2008 investment in next-generation sequencing. This investment has spawned new approaches for looking genome-wide at RNA, transcription factor binding, mutations, and chromatin modifications and translocations.

    Noteworthy aspects of 2014 mentioned by Dr. Siegel included:

    • The newest IRP faculty member is Dr. Markus Hafner in the RNA Molecular Biology Group. Dr. Hafner is an RNA biologist who has developed a deep-sequencing technique that examines RNA-protein interactions on a genome-wide basis.
    • Two new faculty have joined the Clinical Program: Drs. Andy Mammen (a new tenure track investigator in the Muscle Disease Unit) and Peter Grayson (an Assistant Clinical Investigator in the Vasculitis Translational Research Program).
    • Work from the NIAMS IRP has led to a greater understanding of super enhancers in immune regulation. Dr. Siegel explained that super enhancers are regions of DNA that are clusters of binding for "master transcription factors" and are active sites of transcription. Super enhancers are linked to cell identity and enriched for disease susceptibility loci.
    • IRP researchers have also discovered that metabolism signals epigenetic reprogramming through SIRTl. SIRTl senses metabolic signals and regulates muscle cell differentiation through altering chromatin acetylation.
    • Highlights from the Clinical Program in 2014 include the discovery of three new Mendelian inflammatory diseases stemming from mutations in genes not previously linked to human disease (ADA2, STING, and NLRC4) as well as the expansion of investigational clinical trials.

    Dr. Siegel then described the NIAMS Clinical Program, which has six focused translational research programs in the areas of autoinflammatory diseases, lupus, spondyloarthropathy, outcomes research, vasculitis, and myositis. Its focus is on the rapid translation of discoveries into clinical advances, harvesting the maximum research value from patient cohorts and clinical protocols, taking advantage of IRP resources, and training the next generation of clinical investigators. Because IRP fellows are not eligible for the career development and training programs available to the extramural community, the IRP has developed a program to allow Clinical Rheumatology Fellows to train along a pathway that leads from the Rheumatology Fellowship to the Scholars in Translational Research Program, the Assistant Clinical Investigator position, and eventually, intramural or extramural tenure-track faculty. There is a new initiative within the Clinical Program, the NIH-Children's National Medical Center Joint Pediatric Rheumatology Fellowship.

    Dr. Siegel mentioned that there are several NIAMS IRP investigators who have been recognized with a number of prizes and awards in 2014:

    • Dr. Raphaela Goldbach-Mansky (Acting Chief of the Translational Autoinflammatory Disease Section) was elected to the American Society for Clinical Investigation.
    • NIAMS Scientific Director Dr. John O'Shea was awarded the Ross Prize in Molecular Medicine and was elected to the Institute of Medicine.
    • Dr. Alasdair Steven, Senior Investigator in the Laboratory of Structural Biology Research, was awarded the Eduard Kellenberger Medal from the International Federation of Societies for Microscopy.

    In his concluding remarks, Dr. Siegel noted that the IRP is actively seeking to participate in trans-NIH activities, strengthen intramural-extramural collaborations, and collaborate with industry and the NIH Clinical Center.


    NAMSAC Executive Secretary Dr. Laura K. Moen, Director of the Division of Extramural Research Activities, explained that each year at the winter Council meeting, the Institute renews its understanding with Council members regarding how the Council operates. She presented the Statement of Understanding that describes the Council's operating procedures. No Council members expressed any concerns or had any questions regarding the Statement of Understanding, and the operating procedures were accepted for the next calendar year.


    In closed session, the Council reviewed a total of 850 applications in closed session requesting $1,149,514,897 in total costs and recommended 850 for $1,149,514,897 in total costs.


    This portion of the meeting occurred during closed session.


    This portion of the meeting occurred during closed session.


    The 85th National Arthritis and Musculoskeletal and Skin Diseases Advisory Council Meeting was adjourned at 3:00p.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

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