PROJECT ABSTRACT This is an application for the NIAMS K01 Mentored Research Scientist Development award for Dr. Stephan Bodkin, an Assistant Professor in the Department of Physical Therapy and Athletic Training in the College of Health at the University of Utah. Dr. Bodkin is establishing himself as an emerging leader in sports medicine research, specifically in advancing clinical decision making in returning patients to activity following traumatic joint injuries. This K01 award will provide Dr. Bodkin the support necessary to accomplish the following career development goals: 1) Obtain training in molecular techniques of skeletal muscle cellular remodeling, especially relating to the quantification of intramyocellular lipids and fibrosis, 2) Expand my knowledge in age-related changes to skeletal muscle and cartilage degradation within the lifespan of osteoarthritis diagnosis, 3) Develop expertise needed for clinical interpretation of MRI as it relates to skeletal muscle and cartilage, and 4) Strengthen leadership and research skills required to conduct clinical trials successfully. To achieve these goals, Dr. Bodkin has assembled a mentoring team comprised of a Scientific Mentor, Dr. Micah Drummond, a translational researcher experienced in biological mechanisms of aging skeletal muscle atrophy and regrowth, a Career Mentor, Dr. Jennifer Majersik, a clinical neurologist with a proven track record of mentoring junior faculty members, and 5 advisors with expertise in aging medicine (Dr. Mark Supiano), biostatistical design and analysis (Mr. Greg Stoddard), clinical imaging (Dr. Glenn Morrell), orthopedic surgery (Dr. Travis Maak), and skeletal muscle function following joint injury (Dr. Lindsey Lepley). Dr. Bodkin’s work has well documented skeletal muscle weakness following anterior cruciate ligament reconstruction (ACLR) and the inability to restore strength despite undergoing traditional post-operative rehabilitation. This work and others suggest potential physiological contributors to skeletal muscle weakness following ACLR. Based on recent evidence, Dr. Bodkin’s central hypothesis is that ACL injury and reconstruction promotes the infiltration and development of muscle adiposity which thus impairs muscle strength. He will test this hypothesis by serially quantifying intramuscular adipose tissue (IMAT) and intramyocellular lipids (IMCL) in patients undergoing ACLR and relating measures of muscle adiposity to strength. These outcomes will be collected in young and middle-aged adults, exploring potential interactions of age and traumatic injury on skeletal muscle remodeling. By pursuing the following specific aims, the applicant will test his hypothesis and gather data for a subsequent R01 application to investigate rehabilitation interventions on skeletal muscle biology following traumatic joint injuries. Specific Aim 1 will determine the influence of ACLR on quadriceps adiposity by quantifying IMAT and IMCL pre-ACLR, 2 weeks post-ACLR, and 3 ...