INBRE: MUSC: ENHANCEMENT OF BIOENGINEERING PROGRAM AT MUSC

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. MUSC is committed to the success of the INBRE network and will provide institutional support through the Department of Regenerative Medicine & Cell Biology, when needed, to supplement INBRE funding of core facilities (detailed in Section G of this competitive renewal application) and mentored, target faculty pilot (seed) projects. This program has been instrumental in developing multiple grant submissions to both federal and private agencies. The Department of Regenerative Medicine will allocate sufficient institutional support to assure that target faculty have protected time as required by the NCRR guidelines, a full time technician and supplies sufficient to cover animal and other costs. As in the current SC INBRE grant, target faculty will have full access without cost to all INBRE and COBRE cores. Each pilot project faculty person will have a target mentor and also will be expected to participate in monthly mentoring sessions organized on behalf of COBRE and INBRE target faculty. Pilot projects are solicited annually and reviewed by a mentoring team of global COBRE mentors (Drs. Tom Borg, Richard Swaja, Dr. Martin Morad) and both Drs. Markwald and Argraves. To compete for a pilot project, a specific 4 page proposal is required, in the format shown in Dr. Ghatak's project, target project for year one of the new SC INBRE. All projects have been based on a regenerative medicine theme that directly can be related to a "Cycle of Discovery" format. By the latter, we mean a cycle that starts with the identification of genes in a patient population with either a cardiac developmental (birth) defects or an adult cardiovascular disease (e.g. mitral valve prolapse). Once the gene is identified, animal or culture models are established to understand mechanisms and potential therapeutic targets. Pharmacological or molecular approaches are used to determine if inhibiting or stimulating potential targets modifies progression or outcome of the disease. Translational trials are then set up to test the pharmacological agent in human patient populations, thus completing the cycle. A paradigm for the cycle of discovery would be losartan treatment for Marfan's syndrome, which was determined by identifying the genetic mutation (fibrillin), its mechanism and a therapeutic target (TGF beta signaling). The pilot project described in this competitive renewal application for SC INBRE is based on the finding that a matricellular protein, CCN1, when mutated, causes human atrioventricular septal defect or valve lesions to varying degrees in children.