Project Grant P20DK140417

VALIDATING MOUSE MODELS OF PROSTATIC HYPERPLASIA - OVERALL: SUMMARY THIS P20 FORWARD CENTER WILL SUPPORT A PROJECT CONCEIVED AND EXECUTED BY THREE EARLY STAGE INVESTIGATORS (ESIS) TO ADDRESS A PROBLEM THAT IS IMPORTANT TO THE FIELD OF BENIGN PROSTATE RESEARCH AND TO OTHER FIELDS MORE BROADLY: THE RELEVANCE OF SPECIFIC GENETICALLY ENGINEERED MOUSE MODELS TO HUMAN DISEASE. THE NEED FOR ANIMAL MODELS IN BIOMEDICAL RESEARCH AND THE UTILITY OF MICE, SPECIFICALLY, IS WELL RECOGNIZED AND ACCEPTED. A NUMBER OF MOUSE MODELS THAT PURPORT TO REPRESENT THIS DISEASE HAVE BEEN GENERATED. IT IS WELL RECOGNIZED IN THE FIELD THAT NONE OF THESE IS A GOOD OVERALL REPRESENTATION OF THE HUMAN CONDITION. AS SUCH, CRITICISM OF MODELS IS A COMMON ISSUE IN GRANT AND PAPER REVIEW. THIS IS A PROBLEM FOR ALL INVESTIGATORS IN THE FIELD AND CAN BE PARTICULARLY DAMAGING TO ESIS WHO DO NOT HAVE RESOURCES TO GENERATE DATA FROM MULTIPLE LINES. THE CENTER WILL BRING TOGETHER TWO BIOLOGISTS (DRS. POPOVICS AND VICKMAN) WITH COMPLEMENTART SKILL SETS AND AN INTEREST IN BPH, , CONTRIBUTING EXPERTISE IN MOUSE MODELS AND INFLAMMATION, WITH A BIOINFORMATICIAN (DR. LANMAN) TO DEVELOP NEW APPROACHES TO CORRELATE TRANSCRIPTOMIC DATA FROM MICE WITH EXISTING HUMAN BPH DATASETS TO ESTABLISH A REFERENCE DTABASE ENCOMPASSING SIMILARITIES AND DIFFERENCES BETWEEN INDIVIDUAL MOUSE MODELS AND SALIENT ASPECTS OF HUMAN DISEASES. SUCCESSFUL DEVELOPMENT OF THESE METHODS WILL ALLOW BROAD APPLICATION OF THE APPROACH ACROSS A RANGE OF DISEASES WHERE SUCH PROBLEMS EXIST. THE PROJECT WILL ESTABLISH STANDARDS AND BENCHMARKS FOR COMPARING MOUSE MODELS TO HUMAN BPH AND IDENTIFYING COMMONALITIES AND DISPARITIES BETWEEN THE TWO. THIS WILL FACILITATE THE SELECTION OF THE BEST MODELS AND WILL ENCOURAGE SIMILAR CHARACTERIZATION AND COMPARISON OF OTHER MODELS IN THE FIELD. THE DATA WILL BE MADE AVAILABLE TO THE SCIENTIFIC COMMUNITY, AS A COLLECTION IN THE CELLXGENE PORTAL AND AS AN RSHINY APPLICATION. CONSISTENT WITH THE STATED GOALS OF THE RFA THE ADMINISTRATIVE CORE AND ITS DIRECTOR (THE PI, DR. HAYWARD) WILL SUPPORT THE PROJECT AND SPECIFICALLY WILL PROVIDE ACCESS TO RESOURCES AND EXPERTISE TO ASSIST THE THREE ESIS IN THE DEVELOPMENT OF NEW FUNDING PROPOSALS DERIVATIVE FROM THE DATA GENERATED HERE. THE ADMINISTRATIVE CORE WILL ALSO OVERSEE THE FISCAL AND REGULATORY ASPECTS OF THE CENTER AND WILL PROVIDE MECHANISMS FOR REGULAR CONTACTS BETWEEN THE PROJECT INVESTIGATORS AND THE BROADER RESEARCH COMMUNITY, IN PARTICULAR WITH PAST AND PRESENT CAIRIBU MEMBERS, FOSTERING OPPORTUNITIES TO PRESENT DATA AND FURTHERING CAREER OPPORTUNITIES. THE ADMINSTRATIVE CORE WILL ALSO COORDINATE WITH EXPERTS IN THE FIELD TO SUPPORT THE DEVELOPMENT AND SUBMISSION OF NEW GRANT PROPOSALS FROM THE ESIS. THE IMMEDIATE GOAL OF THIS CENTER IS TO SUPPORT THE DEVELOPMENT OF DATA THAT WILL CONTRIBUTE TO THE CAREER DEVELOPMENT AND FUNDING SUCCESS OF THREE EARLY STAGE INVESTIGATORS IN THE FIELD OF BENIGN UROLOGIC RESEARCH, BRING NEW IDEAS AND RETAIN EXPERTISE IN THE FIELD. THE LONG-TERM GOAL IS FOR THE ESIS TO ACHIEVE SIGNIFICANT INDEPENDENT CAREERS.