Centers of Research Translation (CORT) Grant (P50)
The P50 Center of Research Translation CORT Program was initiated in 2006 and has had a transformative impact on the musculoskeletal research program at the University of Rochester. The Program has focused the collective efforts of an experienced, talented, and multi-disciplinary research team. The objective of the CORT Program is to translate understanding of the molecular, cellular, and tissue responses involved in musculoskeletal disease. The current Center of Research Translation on the Osteoimmunology of Bone Infection (CoRTOBI) builds on the remarkable successes of previous programs that lead to numerous high impact publications, R01 NIH grants, patents, clinical trials, and faculty promotions, including four academic Chairs in prestigious institutions.
CORTBI is focused on musculoskeletal infections, which remains the bane of elective total joint replacement (TJR) surgery, of which the vast majority is caused by Staphylococcal species. Staphylococcus aureus causes most orthopaedic infections, and methicillin-resistant S. aureus (MRSA) acquired in both hospital and community settings are responsible for the most severe phenotype. The current CORTBI program aims to advance and translate the major discoveries from investigators within the CMSR. These include: 1) S. aureus colonization of the osteocytic-canalicular network of live bone, 2) novel antibiotics that specifically target these mechanisms, which can be 3D-printed into custom spacers; and 3) development of a custom multiplex Luminex assay to elucidate the immune proteome of S. aureus during orthopaedic infections. The significance of the proposed CoRTOBI spans: the great unmet clinical needs in PJI; our limited understanding of the microbial pathogenesis and host response during S. aureus infection of bone; the crippling health care costs of PJI; and the political and ethical dilemmas that resulted from PJI healthcare reform.
Osteoimmunology Core: This Research Core comprises a multidisciplinary team of investigators with extensive experience in bone pathology, microbial pathogenesis, immunology, TEM and Confocal imaging, material science & engineering, infectious disease and orthopaedic surgery, to develop the equipment and protocols. The core is responsible for:
- Comprehensive EM Core services including SEM and TEM imaging
- Fabricate nanoporous membranes for in vitro characterization of S. aureus migration
- Fabricate antibiotic 3D-printed composite calcium phosphate and collagen scaffolds
- Perform custom multiplex Luminex assays to assess S. aureus humoral immunity during infection
Project 1: Understanding the mechanisms of S. aureus invasion of osteocytic-canalicular network of live bone (haptotaxis and durotaxis), identifying novel drug targets, and exploring the potential of localized delivery using 3D-printed antibiotic-impregnated spacers for 1-stage revision surgery.
Project 2: Deciphering the protective versus susceptible nature of an individual’s immune response against S. aureus during osteomyelitis and understanding why patients with the same MRSA PJI have dramatically different outcomes including septic death?
Administrative Core: These projects are supported by an experienced team of CMSR investigators and administrators lead by the Center Director, Dr. Edward M. Schwarz, the Richard and Margaret Burton Distinguished Professor of Orthopaedics.
The Program has the entire constellation of factors necessary for success, including:
- A collaborative research team
- An exceptional research infrastructure that permits comprehensive experimental approaches
- A history of scientific innovation and commitment to translational research
- Excellent integration of and access to institutional research resources and facilities by a talented research team