Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome

Somatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing. We find that haematopoietic cells expressing mutant U2AF1(S34F), including primary patient cells, have an increased sensitivity to in vitro sudemycin treatment relative to controls. In vivo sudemycin treatment of U2AF1(S34F) transgenic mice alters splicing and reverts haematopoietic progenitor cell expansion induced by mutant U2AF1 expression. The splicing effects of sudemycin and U2AF1(S34F) can be cumulative in cells exposed to both perturbations—drug and mutation—compared with cells exposed to either alone. These cumulative effects may result in downstream phenotypic consequences in sudemycin-treated mutant cells. Taken together, these data suggest a potential for treating haematological cancers harbouring U2AF1 mutations with pre-mRNA splicing modulators like sudemycins

Community Visioning for Marysville, Kansas: A three-part study comprised of a housing conditions inventory, city-wide brownfield redevelopment concepts, and ideas for transforming the Union Pacific Depot site into a regional destination

The Marysville Chamber of Commerce and Visitor’s Center and the City of Marysville collaborated with Kansas State University’s Department of Landscape Architecture and Regional & Community Planning (LARCP) and K-State’s Technical Assistance to Brownfields (TAB) for the spring and fall semesters in 2019. The intent of the collaboration was threefold: to document housing assets in the community, generate a set of strategic urban design ideas, and develop site planning alternatives for the Union Pacific Depot brownfield site. The effort was co-led by Associate Professor Blake Belanger and Assistant Professor Susmita Rishi. Professor Rishi and her students conducted a housing conditions inventory as part of PLAN650 Housing and Development Programs in the spring semester of 2019. She directed a different group of students to develop a set of urban design strategies in the fall semester of 2019 in PLAN640 Urban Design and Development Seminar. Also, during fall 2019, Professor Belanger led a group of students in LAR442 Site Research and Design Studio to develop design alternatives for the historic Union Pacific Train Depot site and adjacent parcels. Students shared their findings of PLAN640 and LAR442 in a public exhibit and open house on November 6, 2019. The agreement was mutually beneficial. Marysville leaders and decision-makers received fresh ideas, and students had the opportunity to work with external collaborators on a community engagement project. The City of Marysville funded the housing inventory during Phase 1 of the project and K-State TAB funded Phase 2 through an Environmental Protection Agency (EPA) Small Community Technical Assistance Grant (SCTAG) from the Kansas Department of Health and Environment (KDHE). In addition to the student work, Sustainable Strategies DC prepared a Resource Roadmap and TAB provided a summary of the November 6, 2019 public open house. In total, the contributors included 2 professors, 57 students, and 2 professionals