PROJECT SUMMARY/ABSTRACT The efforts described in this second phase CoBRE application will support the Center of Excellence within the West Virginia University Health Sciences Center (WVU HSC) that focuses on studies of the tumor microenvironment (TME), designated the TME CoBRE. The overarching critical need for continued emphasis in this area is driven, in part, by that fact that cancer mortality is a significant health disparity in the Appalachian region, specifically in West Virginia. We are building on a successful Phase I, where we had two graduates with R01s, a major national foundation grant, a NSF grant, an R21 and our cores were awarded two S10 awards. In total we had 11 Project Leader (PL) awards as PI, and 8 as a Co-I. The Center has grown to over 20 faculty, including a number of faculty who are potential PLs, with their teams publishing over 140 papers since initiation of Phase I. Laboratories supported, in part, by the Phase I TME CoBRE, have engaged in the training of ~60 students further amplifying the impact of the NIGMS investment on workforce development in parallel to CoBRE PL success. Herein, we provide details for the strategy to continue to develop careers of promising junior scientists and recruit additional investigators to study the biology of, and novel therapeutic approaches that will benefit from, a mechanistic understanding of the diverse TME. The five highly translational projects in Phase II focus on the microenvironment of different tumor types, including cancers initiating in the bone marrow, gastric system, breast, and brain. The administrative core will manage the overall budget and provide assistance in annual reporting and submission of extramural applications of all CoBRE Project Leaders. In addition, this core will provide oversight of mentoring, which includes two primary advisors for each investigator as well as an external advisor, and a network of previous CoBRE graduates and the Director of Core Resources. The investigators will be supported by two research cores that leverage past and current CoBRE and IDeA support. Single cell analysis capability in the existing flow cytometry core will aid to it investigations into genomics of single cells. The Imaging Core will support PLs with cutting edge technologies including microbeam irradiation, microCT, pre-clinical MRI, and real time microenvironment imaging of pO2 and pH. Lastly, we will continue to administer a pilot project program to recruit new junior faculty to the TME CoBRE, as we saw five of six pilot grant awardees eventually become PLs, and we currently have a robust number of junior investigators (#5) may become PLs as well. The investigators are well integrated into established programmatic areas in the West Virginia University Cancer Institute that meet every other month for focused discussion on therapies that leverage, and the biology of, the TME. The mentoring atmosphere, core facilities, and significant institutional support that are central to this effort will continue to provide a rich environment to nurture investigator independence and success around the critical scientific area of TME.

PROJECT NARRATIVE Signaling between tumor cells and their host environment that results in enhanced tumor cell survival via diverse mechanisms, growth and promotion of invasion into other tissues. Most cancer victims succumb to their disease because of the size of the tumor and/or metastases to different organs. This CoBRE will 1) increase our mechanistic understanding of the interaction between the tumor and its environment, 2) position junior faculty for success by improving competitiveness for extramural support through diverse training opportunities and specific mentoring strategies and 3) support critical infrastructure for the projects of focus in the current application but also to recruit additional tumor microenvironment focused scientists to West Virginia.