Center of Biomedical Research Excellence in the Molecular Basis of Human Disease--Project 4

The overall objectives of the COBRE in the Molecular Basis of Human Disease at the University of Kentucky continue to be: (I) enhancing multidisciplinary research on the study of human disease, (ii) enhancing research competitiveness of the junior faculty who serve as principal investigators on research projects and pilot projects, and (iiG building and strengthening new core facilities to enhance the research capabilities of the principal investigators. their co-investigators, and researchers throughout the University. Significant progress has been made to achieve these objectives. This past year three of the current COBRE Pis submitted new research grants. with two new grants received. Only the two new COBRE Pis (201012011) did not submit grants. COBRE faculty published or have in press over 33 papers this past year and made 16 presentations at conferences and meetings. . The core facilities supported by this COBRE grant continue to be broadly used by the COBRE faculty. The external advisory board met at the University in October of 201 0 and heard presentations from each of the principal investigators and core directors. Fallowing these meetings the external advisory board met with the PI Dr. Hersh and reviewed the progress of the projects and cores. This information was subsequently passed on to the junior faculty Pis, pilot grant Pis, and core directors. All projects were deemed to be progressing, however It was recommended to decrease the funding of one project. In addition, two new faculty Pis, Dr. Emilia Galperin and Dr. Yvonne Fondufe-Mittendorf, were recruited to UK and. based on the recommendation of the extemal advisory board, made Pis on COBRE projects. Dr. Galperin's project is entitled ·Understanding the role of Shoc2 protein in spatio-temporal regulation of extracellular signal-related kinase (ERK) kinase cascade: and Dr. Fondufe-MiUendorfs project is entitled "A study into understanding the molecular basis of epigenetic transcriptional silencing." The COBRE mentors and Pis continued to meet on a biweekly basis throughout the year. During this time the COBRE principal investigators and pilot project investigators made informal presentations, and discussed their projects, grant writing, publications, etc. These mentoring sessions prove to be very effective and useful for facilitaUng the research projects and for stimulating the junior faculty. The COBRE mentors began meeting on a monthly basis as an advisory group to review progress of the Pis and to evaluate cores. We contlnued our training program on ethical and responsible conduct in research. All of the trainees involved in the grant participated and will continue to participate in this training program. This year one new pilot award was made to facilitate program project applications. The title of the project funded is "The roles of integrin-daudin protein complexes in metastatic and chemoresistant human breast cancer". In addition through a supplemental NCRR ARRA grant a new core for the production of viruses for research was contInued. In addition to our regular research project, we have one Plannint Grant committee, supported by funds awarded in the Administrative Core, with faculty who are working to generate preliminary data for a multi-PI or program project grant application. Planning grant to determine the role of the RNA processing protein FUSrrLS in ALS (Zhu) This planning grant group consists of Drs. Halning Zhu, Jianhang Jia. and Stefan Stamm. The central hypotheSis of the application is that the ALS-related mutations in FUS impair the protein's RNA processing function and ultimately cause motor neuron degeneration. This application is to use a combination of techniques including biochemistry, cell biology. RNA biology and Drosophila genetics, to determine what RNA processing capabilities of FUS are impaired by the ALS-related mutations, and how such dysfunction can cause motor neuron death.