Abstract
The Achilles Tendinopathy Center of Research Translation (AT-CORT) at the University of Pennsylvania will
foster fundamental discoveries to guide clinical translation, as well as develop and employ novel translational
resources, models and technologies, to address the highly significant research and clinical challenge of Achilles
tendinopathy. Despite the high frequency and increasing prevalence of tendinopathy in young and old patients,
and the significant pain and disability that arises from this condition, as well as the associated high cost to society,
effective treatment modalities have stagnated over the last two decades. This is due to the lack of fundamental
understanding of tendon disease etiology and pathogenesis, which limits development of novel treatment
modalities. At present, beyond surgical intervention for late-stage disease, the only approved clinical therapy
involves physical interventions via controlled rehabilitation mechanical loading of the tendon. While efficacious
in some patients, outcomes of this intervention do not stem disease progression in most patients. Given the
central mechanical role of the Achilles tendon, and the critical role of mechanical loading and mechanobiology
on tendon cell homeostasis, it is critical that we develop and expand our understanding of the role of mechanical
forces in disease onset and progression to optimize existing and inform new treatment strategies. Our proposed
AT-CORT is uniquely positioned with a critical mass of multidisciplinary scientists and clinicians with strong
interest and expertise in these and related areas. The Overall goal of the AT-CORT is to develop new insight
and technologies that uncover the mechanobiologic basis of Achilles tendinopathy across length scales, from
the nucleus, to the cell, to the tissue microenvironment to patients. We will assess these critical elements during
disease onset and progression, informed by both vivo animal models that replicate disease processes and
source material and real-world loading data from living human subjects. The AT-CORT is comprised of four
independent and yet interactive elements, including an Administrative Core to oversee and guide interactions
and primary Research Projects focused on the transfer of information from the external tendon cell
microenvironment through the cytoskeleton (Project 1) and on chromatin remodeling and mechano-epigenetic
regulation of tendon cell phenotype (Project 2). Using cells, tissue, and loading information derived from both
human and animal tendinopathic models (Tissue Core), these research projects will advance our knowledge of
the origins of tendinopathic disease and define new avenues for therapeutic intervention. Together, our highly
interdisciplinary team, innovative tools, and outstanding and interactive Research Projects and Cores will
dramatically advance knowledge, develop innovative tools and insight, and provide new directions for translation
of novel therapies to treat Achilles tendinopathy.