PROJECT SUMMARY Although the survival for other cancers improved during the last ten years, the outlook for pancreatic ductal adenocarcinoma (PDAC) remains grim. The average overall 5-year survival rate for PDAC is 10.8%. The mission of the Center for Diagnostic and Therapeutic Strategies in Pancreatic Cancer (CDTSPC) in Phase II is to enhance and sustain biomedical research infrastructure at North Dakota State University (NDSU) by developing externally-funded, independent translational research of the Junior Investigators, expanding Core Facility services, and recruiting new investigators. The Covid pandemic-related restrictions hampered our progress in Phase I. Still, the investigators received seven nationally competitive research grants totaling $9.6 million, published more than 50 papers, and graduated 17 Ph. D. students. Two Junior Investigators and three pilot project leaders received tenure and promotion. NDSU hired four new Assistant Professors with research emphasis on pancreatic cancer. Two new Core Facilities were set up – Animal Studies and Biostatistics. The two facilities served 19 COBRE and 33 other investigators. The Animal Core Facility created comprehensive mice models for the first time on campus, including 7 patient-derived mouse models (PDX) of pancreatic cancer. CDTSPC is the only established Facility in North Dakota with the capacity to support foundational and translational research on pancreatic cancer. In Phase II, we will further expand the biomedical infrastructure, emphasizing translational research and prepare for a self-sustaining Center through the following Specific Aims. Aim 1. Provide enhanced mentoring to develop sustainable, independent, translational research projects for Junior Investigators. The three investigators will address three urgent challenges in pancreatic cancer: targeted drug delivery to desmoplastic tumors, synthesis and evaluation of new therapeutic agents, and determining epigenetic-genetic alternations in patient tissues for effective treatment. Each Junior Investigator will have two external mentors to encompass foundational and translational aspects. In addition, a clinician-scientist will serve as the Translational Science Liaison for the Center to bridge the foundational and translational elements. Aim 2. Augment biomedical research infrastructure of NDSU by expanding COBRE Core Facilities. We will expand the Animal Studies Core Facility to include tissue histology, imaging modalities, establish and maintain additional genetically engineered models, continue developing the PDX model systems, and establish a tissue biobank of human, PDX, and mouse pancreatic cancer tissues. In addition, the Biostatistics Core Facility will expand services to support projects using "big data," bioinformatics, and machine-learning analysis. Aim 3. Integrate the Center into the national pancreatic cancer network. We will expand collaboration with eminent pancreatic cancer researchers in the US. We will build human capacity by hiring two new tenure track faculty members and recruiting four new Pilot Project investigators with expertise in translational aspects of pancreatic cancer. The Junior Investigators will compete for grants from NIH, NSF, DoD, and private foundations.

PROJECT NARRATIVE CDTSPC is the first and only COBRE Center in North Dakota dedicated to foundational and translational studies on pancreatic cancer. In Phase II, the Center will emphasize translational aspects and expand sustained research funding opportunities for the Junior Investigators. The proposed expansion of research infrastructure will augment the critical mass of researchers, Core Facilities, and equipment at NDSU, resulting in a nationally recognized, self-sustaining Center on pancreatic cancer.