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1 OMB No and (Rev. 10/15 Approved Through 10/31/2018) NAME: Crofford, Leslie J. POSITION TITLE: Professor BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. era COMMONS USER NAME (credential, e.g., agency login): CROFFORD EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) INSTITUTION AND LOCATION DEGREE (if applicable) Completion Date MM/YYYY FIELD OF STUDY Vanderbilt University, Nashville, TN B.A 05/1980 Chemistry University of Tennessee, Memphis, TN MD 06/2984 Medicine Barnes Hospital, Washington Univ, St. Louis, MO 06/1987 Internal Medicine NICHD/NIH, Bethesda, MD 10/1989 Molecular Biology NIAMS/NIH, Bethesda, MD 07/1993 Rheumatology A. Personal Statement As Division Director for Rheumatolgy & Immunology, I have responsibility for administration, research support, educational activities, and clinical programs with the assistance of many our our outstanding faculty, all of whom have significant roles in the operations of our Division. I have a a long-standing interest in training fellows and junior faculty in clinical, translational, and basic science methodology. I was PI of a T-32 for training of arthritis investigators at the University of Michigan and am delighted that Dr. James W. Thomas has successfully renewed our T-32 at Vanderbilt. I have served as President of the Rheumatology Research Foundation, which has as its highest goal to facilitate development of physician scientists in arthritis research. During that time, I served on the executive committee of the board of directors of the American College of Rheumatology. I also served on the Advisory Council of the National Institute of Arthritis and Musculoskeletal and Skin diseases which a special interest in working with institute staff on developing a pathway to success for physician scientists. Currently, I serve on the Arthritis and Musculoskeletal and Skin Study Section of NIAMS that reviews training and career development awards. Additionally, I am deputy editor of Arthritis Care & Research, one of the two journals of the American College of Rheumatology. It is my over-arching goal to continue the growth and development of the Division of Rheumatology & Immunology at Vanderbilt. B. Positions and Honors Positions and Employment: Medical Staff Fellow. Human Genetics Branch and Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD Medical Staff Fellow. Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD Assistant Professor of Internal Medicine, Division of Rheumatology, University of Michigan Associate Professor of Internal Medicine, Division of Rheumatology, University of Michigan 2004 Professor of Internal Medicine, Division of Rheumatology, University of Michigan 2004-present Professor of Internal Medicine, Division of Rheumatology, University of Kentucky 2004-present Chief, Division of Rheumatology, University of Kentucky 2004-present Gloria W. Singletary Chair and Director, Center for the Advancement of Women s Health, University of Kentucky Program Director, General Clinical Research Center, University of Kentucky Professor, Department of Microbiology, Immunology and Genetics, University of Kentucky

2 Director, Clinical Services Core, Center for Clinical and Translational Science, University of Kentucky 2013-present Professor, Department of Medicine, Division of Rheumatology & Immunology, Vanderbilt University Associate Director, Division of Rheumatology & Immunology, Vanderbilt University 2014-present Director, Division of Rheumatology & Immunology, Vanderbilt University 2014-present Professor, Department of Pathology, Microbiology & Immunology, Vanderbilt University 2016-present Wilson Family Chair in Medicine Honors 1980 Magna Cum Laude, Vanderbilt University 1984 Alpha Omega Alpha, University of Tennessee Health Sciences Center 1992 American College of Rheumatology Senior Rheumatology Scholar Award 1994 RV Satterfield Arthritis Investigator Award, Arthritis Foundation 1996 Central Society for Clinical Research 1999 Jerome W. Conn Award for Distinguished Research by a Junior Faculty Member, Department of Internal Medicine, University of Michigan 2004 Gloria W. Singletary Chair in Women s Health Research, University of Kentucky 2007 President, American College of Rheumatology Research and Education Foundation 2009 NIAMS Advisory Council 2011 Physician-in-Chief Pro Tempore, Hospital for Special Surgery 2011 Woman in Inflammation Science Award, International Association of Inflammation Societies 2013 American Clinical & Climatological Society 2014 Association of American Physicians C. Contribution to Science 1. In 1989 when I began my post-doctoral work at NIAMS, I was interested in the role of neuroendocrine immune control of autoimmune inflammatory arthritis. In addition to examining the role of neuropeptides in peripheral tissues, we began to study the role of dynamic changes to hypothalamic pituitary adrenal axes in murine models and patients with rheumatoid arthritis. We were the first to report corticotropin releasing hormone expression in peripheral tissues. We were also the first to report the role of circadian variation in HPA axis hormones and their effects on pro-inflammatory cytokines such as interleuking-6. a. Cash JM, Crofford LJ, Gallucci WT, Sternberg EM, Gold PW, Chrousos GP, Wilder RL. Pituitaryadrenal axis responsiveness to ovine corticotropin releasing hormone in patients with rheumatoid arthritis treated with low dose prednisone. J Rheumatol 1992; 19: b. Crofford LJ, Sano H, Karalis K, Webster EL, Goldmuntz EA, Chrousos GP, Wilder RL. Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis. J Clin Invest 1992; 90: c. Crofford LJ, Karalis K, Sano H, Friedman T, Epps H, Remmers EF, Mathern P, Chrousos GP and Wilder RL. Corticotropin-releasing hormone in synovial fluids and tissues of patients with rheumatoid arthritis and osteoarthritis. J Immunol 1993; 151: d. Crofford LJ, Kalogeras KT, Mastorakos G, Magiokou M-A, Wells J, Kanik KS, Chrousos GP and Wilder RL. Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: Paradoxical failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab 1997; 82: In studying the peripheral effects of glucocorticoids during our HPA axis studies, we decided to focus on regulation of prostaglandins. At the time (1989), it was thought that GC exerted their effects by regulating lipocortin-1. We discovered, however, that cyclooxygenase (COX) protein, but not mrna were regulated by GC in arthritis. It turned out that we had identified the properties of COX-2 and when it was cloned, we confirmed our findings at a molecular level. Subsequently, my group was also the first to study regulation of the terminal PGE 2 biosynthetic enzyme microsomal PGE synthase-1 which is also strongly GC regulated. We continue to refine our understanding of the regulation and role of PG in inflammatory arthritis, demonstrating an important effect. a. Crofford LJ, Wilder RL, Remmers EF, Epps, HR and Hla T. Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues: Effects of interleukin-1β, phorbol ester, and corticosteroids. J Clin Invest 1994; 93:

3 b. Stichtenoth DO, Thoren S, Bian H, Peters-Golden M, Jakobsson P-J, Crofford LJ. Microsomal prostaglandin E synthase is regulated by pro-inflammatory cytokines and glucocorticoids in primary rheumatoid synovial cells. J Immunol 2001; 167: c. Kojima F, Kapoor M, Yang L, Fleishaker EL, Ward MR, Monrad SU, Kottangada PC, Pace C, Clark J, Woodward JG, Crofford LJ. Defective generation of a humoral immune response is associated with a reduced incidence and severity of collagen-induced arthritis in microsomal prostaglandin E synthase-1 null mice. J Immunol. 2008; 180: d. Kojima F, Frolov A, Matnani R, Woodward JG, Crofford LJ. Reduced T-dell-dependent humoral immune response in microsomal prostaglandin E synthase -1 null mice is mediated by nonhematopoietic cells. J Immunol. 2013; 191: Also building off our original studies of HPA axis function in rheumatic diseases. We made the observation that patients with fibromyalgia have alterations of the HPA axis. This observation set in motion a series of studies on the physiology of patients with FM. In addition to our studies of the HPA axis, we have identified alterations in the autonomic nervous system, cognition, and sleep physiology. A number of other studies have demonstrated the relationship between the chronic pain of FM and psychological and behavioral changes such as failure of self-regulation. I have also been involved in developing treatments for FM including pharmacologic and non-pharmacologic approaches. a. Crofford LJ, Pillemar SR, Kalogeros K, Cash JM, Michelson D, Kling MA, Sternberg EM, Gold PW, Chrousos GP and Wilder RL. Hypothalamic-pituitary adrenal axis perturbations in patients with fibromyalgia. Arthritis Rheum 1994; 37: b. Crofford LJ, Young EA, Engleberg NC, Korszun A, Brucksch CB, Brown MB, Demitrack MA. Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromylagia and/or chronic fatigue syndrome. Brain, Behavior, and Immunity 2004; 18: c. Chervin RD, Teodorescu M, Kushwaha R, Deline AM, Brucksch CBB, Ribbens-Grimm C, Ruzicha DL, Stein PK, Clauw DJ, Crofford LJ. Objective measures of disordered sleep in fibromyalgia. J Rheumatol. 2009; 36: d. Eisenlohr-Moul TA, Crofford LJ, Howard T, Yepes JF, Carlson CR, de Leeuw R. Parasympathetic reactivity in fibromyalgia and temporomandibular disorder: Associations with sleep problems, symptom severity, and functional impairment. J Pain Dec 23. pii: S (14) doi: /j.jpain [Epub ahead of print]. 4. Studies in patients with FM, who describe important symptoms of myalgia, focused our attention on skeletal muscle physiology in patients with non-inflammatory and inflammatory rheumatic diseases. We developed and performed studies testing a role of autonomic dysregulation of dynamic blood flow in patients with FM. With the knowledge of muscle physiology we gained during those studies, we have turned our attention to changes in myositis and to skeletal muscle in animal models and patients with inflammatory arthritis, studies of which are ongoing. a. Srikuea R, Symons TB, Long DE, Lee JD, Yu S, Chomentowski PJ, Yu G, Crofford LJ, Peterson CA. Fibromyalgia is associated with altered skeletal muscle characteristics which may contribute to post-exertional fatigue in post-menopausal women. Arthritis Rheum. 2012; 65: b. Yu S, Gurley K, Symons B, Long D, Srikuea R, Crofford LJ, Peterson CA, Yu G. Noninvasive optical characterization of muscle blood flow, oxygenation, and metabolism in women with fibromyalgia. Arthritis Res Ther. 14:R236, c. Hanaoka BY, Cleary LC, Long DE, Srinivas A, Jenkins KA, Bush HM, Starnes CP, Rutledge M, Duan, J Fan Q, Fraser N, Crofford LJ. Physical impairment in patients with idiopathic inflammatory myopathies is associated with the American College of Rheumatology functional status measure. Clin Rheumatol Nov 12 [Epub ahead of print] d. Cleary LC, Crofford L, Long D, Charnigo R, Clasey J, Beaman, F, Jenkins KA, Fraser N, Srinivas A, Chaon N, Hanaoka BY. CT based muscle density predicts muscle function and health-related quality of life in patients with idiopathic inflammatory myopathies. Arthritis Care Res Jan 26. doi: /acr [Epub ahead of print]. A link to my full citation list can be found at =ascending

4 D. Research Support Current Projects: Rheumatology Research Foundation (Crofford, PI) 07/01/14-06/30/17 (no cost ext) Peripheral mechanisms of fatigue in inflammatory arthritis The goal of this study is to determine the effect of inflammation on skeletal muscle physiology and how this relates to the symptom of fatigue in patients with rheumatoid arthritis and ankylosing spondylitis. Role: PI 2R01AG (Segerstrom, PI) 07/15/06-07/31/17 Self-Regulation, Immunological Aging, and Health in Older Adults The purpose of this project is to measure individual differences and changes in self-regulation over time in older adults and to link self-regulation to subjective health, health risks, and clinically relevant markers of immunological aging, including inflammation and markers of lymphocyte terminal differentiation and replicative senescence. ROLE: Co-I 1UM1AR (Sluka/Crofford, Co-PI) 05/01/13-01/31/18 Effectiveness of TENS on fibromyalgia pain The goal of this clinical trial planning grant is to complete logistical and feasibility procedures to apply successfully for funding of a two-site clinical trial. R01 AG A1 (Crofford/Segerstrom, Co-PI) 07/01/13-6/30/18 Pain and well-being in older women: The role of activity and motivation This is a longitudinal study of the roles played by activity and motivation as moderators of pain and eudemonic well-being in older women. Vanderbilt Diabetes Research and Training Center Pilot (Crofford, PI) 04/01/15-03/31/17 Microsomal PGE synthease-1 deficiency in obesity and metabolic syndrome The goals of this project are to understand the mechanisms by which mice with mpges-1 deficiency are resistant to diet-induced obesity. Role: PI Completed Projects: 1R01AR (Reid/Crofford/Westerblad, Co-PI) 09/17/12-08/31/15 Skeletal muscle biology in rheumatoid arthritis The goal of this study is to determine the impact of inflammatory arthritis on skeletal muscle physiology. R01 AR49010 (Crofford) 07/01/02-12/31/14 Microsomal prostaglandin E synthase in Rheumatoid Arthritis The major goal of this project is to use animal models to determine to role of mpges-1 in inflammation and immunity. ROLE: PI R01 HL (King, PI) 11/01/07-01/31/13

5 NIH/NHLBI The role of prostaglandin E2 in angiotensin II-induced vascular disease The goals of these studies are to determine in influence of PGE2 on the development and progression of cardiovascular disease after exposure to ang II. ROLE: Co-I R21 AG (Crofford/Peterson, Co-PI) 09/01/09-08/30/11 Contribution of altered muscle hemodynamics to fatiguability of older persons with and without fibromyalgia The goals of this project are to compare microvascular, macrovascular, and mitochondrial changes in patients with FM compared to fatigued or normal older persons after controlled exercise R34 AR (Sluka/Crofford, Co-PI) 02/02/11-01/31/13 Effectiveness of TENS on fibromyalgia pain The goal of this clinical trial planning grant is to complete logistical and feasibility procedures to apply successfully for funding of a two-site clinical trial. UL1 RR033173/TR (Kern) 06/01/11-02/29/16 NIH/NCRR Kentucky Center for Clinical and Translational Science The major goal of this project is to support clinical and translational science, and develop new investigators in clinical and translational science at the niversity of Kentucky. ROLE: Co-I, Director PCIR, Executive Committee