Program Director/Principal Investigator (Liu, Wei): Abstract The overall goal of this mentored career development award (K23) is to support Wei Liu, PhD to become an independent investigator in the field of complementary and alternative medicine (CAM) and chronic pain, with a focus on biofeedback Tai Chi intervention development and testing. Disabilities that arise from typical impairments of knee osteoarthritis (OA) include decreased muscle strength, reduced range of motion, and decreased aerobic cardiovascular function. A large number of individuals with knee OA experience disability and require rehabilitation. Traditional Tai Chi intervention (TC) has been promising therapeutic intervention for pain reduction in knee OA, but the efficacy of TC as a knee OA intervention have proven inconclusive because individual with knee OA performed TC with widely varying mechanical knee joint loads, this variation could be a confounding factor in any study of TC. Therefore, Dr. Liu proposes a feasibility study in Aim 1 to quantify external knee adduction moment (EKAM), a strong predictor of OA disease severity and progression during TC practice, and in Aim 2, he will introduce real time biofeedback Tai Chi training (BTC) and see if it is feasible to use biofeedback of torque acting on the knee to modify some TC forms by reducing EKAM. In Aim 3, he will conduct a pilot study to determine the feasibility of using optimized BTC training for OA knee pain reduction. The proposed research represents the first study to identify the biomechanical mechanisms of TC exercise (Aim 1 and 2) and target EKAM by using real-time biofeedback approach and manipulate EKAM independently for TC intervention (Aim 3). We can alter medial knee joint loading response of TC. EKAM would be a biomechanical marker for TC intervention associated with clinical outcomes in knee OA. At the completion of the pilot trial in Aim 3, the optimized BTC intervention will be ready to be tested in an R33 to evaluate its efficacy. This proposal represents a 5-year comprehensive mentoring, training and research plan to transition the candidate, Dr. Liu, to a career as a successful independent investigator. By end of the award period, Dr. Liu will have contributed substantially to the field of CAM research. Already an expert on biomechanical approaches to Tai Chi, he will be positioned to become a leader in developing and testing novel CAM interventions in this area, including conducting behavioural clinical trials. OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page Continuation Format Page

Program Director/Principal Investigator (Liu, Wei): Project Narrative/ Public health relevance This project is designed to identify the biomechanical mechanisms of Tai Chi (TC) exercise and test a novel TC intervention by modifying newly identified mechanisms for those with knee osteoarthritis (OA) and to assess the changes in pain associated with the intervention. It combines unique real time torque biofeedback approach, and uses external knee adduction moment (EKAM) as modulation target tailored to TC intervention in this population. The potential benefit from this project is to provide biomechanical insights of TC and this novel TC approach may produce meaningful pain reduction in these patients who can learn and practice safely during this intervention. OMB No. 0925-0001/0002 (Rev. 03/16 Approved Through 10/31/2018) Page Continuation Format Page