PROJECT SUMMARY/ABSTRACT Muscular dystrophies (MDs) occur world-wide affecting all races with an estimated combined prevalence of ~20- 25 per 100,000. Muscle mass is ~65-85% of our body and there are many genetically distinct MDs that affect different body muscles. While mechanistic studies led to some promising therapeutic strategies to slow disease progression, these options are still limited and there is essentially no cure for MDs. Thus, it remains critical to understand the disease mechanisms and utilize the knowledge to develop innovative therapeutic strategies. At University of California, Irvine (UCI), we have strengths in 4 areas of muscle and MD research: (1) muscle immune response/inflammation, (2) muscle regeneration/stem cell biology, (3) epigenetics and gene regulation, and (4) robust clinical and translational research (with strengths in development of biomarkers, natural history studies, validating outcome measurements for interventional studies, and therapeutic development). Together, we believe we can build a robust training program to move the field forward. The major objective of this T32 grant is to cultivate future muscle biology and MD researchers through multidisciplinary training. Mentees will be three predoctoral students and one postdoctoral fellow per year. The T32 program will be affiliated with a newly formed Muscle Biology and Disease Research Center at UCI. UCI is a site for one of the highest number of clinical trials in the US for muscle-related therapy (immune myopathies, muscular dystrophies and rare and ultrarare genetic non-dystrophic muscle disorders). Eighteen mentors have complementary expertise in genomics, epigenetics, immunology, stem cell biology, tissue engineering and clinical research. Each trainee will be co-mentored by a clinician and a basic scientist. The trainees’ development will be supported through didactic teaching, journal club, seminar series, and research in progress meetings on campus as well as opportunities for research presentations at national and international conferences. The T32 program also provides rigorous training for responsible conduct of research and data reproducibility as well as support for career development. Trainees also have opportunities/exposure to the multidisciplinary muscle clinics at UCI (UCI hosts thematic half day clinics in muscular dystrophy, myositis, Pompe Disease and GNE myopathy). There will be opportunities to engage in activities with patient advocacy groups and industry, which would be important to help mentees to understand the impact and the process of possible application of their research in the MD community. Our goal is to train the next generation scientists who can perform rigorous translational research to help MD patients.

PROJECT NARRATIVE Our goal is to build a rigorous training program that enables PhD graduate students and postdoctoral fellows to become translational researchers who seek to understand muscle biology and decipher the mechanisms of its dysfunction in order to develop innovative strategies for effective diagnosis and treatment of muscular dystrophies (MDs). We emphasize highly collaborative multidisciplinary team science with exposure to both rigorous basic and clinical MD research.