Kansas IDeA Network of Biomedical Research Excellence (K-INBRE)

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Project Summary. Parent award description. The Kansas IDeA Network of Biomedical Research Excellence (K-INBRE) is a statewide network of graduate and undergraduate universities in Kansas and Oklahoma that work cooperatively to improve biomedical research in Kansas. Kansas formed such a network in 2001 (Kansas BRIN) and has successfully continued as the Kansas INBRE. The University of Kansas Medical Center (KUMC) is the Lead Institution and works closely with two other Graduate Partner Institutions (GPI) (University of Kansas-Lawrence, KU-L; Kansas State University, KSU;) and seven institutions focused on undergraduate student training [Undergraduate Partner Institution or UPI: Emporia State University (ESU), Fort Hays State University (FHSU), Haskell Indian Nations University (HINU), Langston University (LU, Langston, OK), Pittsburg State University (PSU), Washburn University (WU), and Wichita State University, WSU]. The K-INBRE is focused on 1) ethnic diversity and geographic considerations in our large but sparsely populated state, 2) the power of mentored, team science, and 3) a skilled Kansas workforce and integration with existing educational and training programs. The long-range objectives are to promote multidisciplinary research networks in biomedical research; increase the research base and capacity through research support; provide research opportunities for trainees; serve as a pipeline for students to continue in health research careers; and enhance science and technology knowledge of the Kansas workforce. To achieve the objectives of the K-INBRE functions through 4 Specific Aims and 3 Cores. Aim 1 seeks to improve the multidisciplinary research network in Kansas. The K-INBRE Administrative Core oversees all K-INBRE functions and includes the Incentives & Awards Committee and the Student Research Program. The Communications Core focuses on network communications, scholarship, and internal evaluations. Aim 2 enhances science and technology knowledge through sophisticated bioinformatics technology and education. The K-INBRE Bioinformatics Core focuses on enhanced genomics bioinformatics, bioinformatics education, outreach, and education. Aim 3 stimulates basic, translational, and entrepreneurial research in Kansas via mentored, interdisciplinary research opportunities. The Mentoring Core oversees two mentoring programs and the Developmental Research Project Program. The K-INBRE operates as a very successful program and continues to improve and expand our efforts in biomedical research in Kansas. Research question addressed by the project. Chronic visceral pain is common, occurring both in patients with clinical disease diagnoses (e.g., inflammatory bowel disease, peptic ulcers) and as an idiopathic syndrome without an identifiable structural or physiological abnormality (e.g., disorders of brain-gut interaction (DGBIs), irritable bowel syndrome). Visceral pain management is uniquely challenging, as reflected in the paucity of novel therapeutic development in the last two decades. As a result, novel therapies targeting mechanisms of visceral pain represent a significant public health interest. A primary feature of chronic abdominal pain syndromes is visceral hypersensitivity (VH). Patients exhibit increased mechanical sensitivity to functional stimulation/stretching of the bowel, but the mechanisms responsible for VH remain to be elucidated. One potential therapeutic target is the gut microbiome, particularly the bacteria that colonize the gut and play a key role in maintaining gut homeostasis. Differences in the relative abundance of broad categories of bacteria and specific pathogenic bacteria have been observed between patients with DGBIs and healthy controls. However, most of this work has focused on patients already diagnosed with a DGBI, which requires ongoing symptoms for months before diagnosis, so it is difficult to determine whether these microbiome differences precede or result from the processes underlying VH. We have identified a specific type of commensal gram-positive bacteria, Lachnospiraceae Dorea, that responds dynamically to transient subclinical colon inflammation in mice susceptible to VH. We will answer the question of whether the shifted microbiome is “pathogenic” and can convey VH and, further, we will use modern unbiased approaches to define differences in dynamic microbial colonization, metabolic output from the microbiome, and host gene expression to generate novel therapeutic targets for the treatment of VH. The findings will shed light on the microbiome as a novel therapeutic target specific to VH and provide the next level of support for translational studies of fecal microbiome manipulation for precision abdominal pain management. How this project will benefit from the team science effort. The co-PLs are skilled, productive, independent scientists, but this project demands a breadth of knowledge and diversity of expertise greater than any single investigator or lab. This collaboration has the potential to produce data of greater scientific impact, innovation, and intellectual reach by focusing diverse perspectives on solving the “problem of pain” and creating a new category of multi-omic pain research incorporating the microbiome, metabolome, host transcriptomes into the development of novel therapeutics. If funded, we believe this project marks the beginning of a new line of research for each co-PLs and a vehicle for continued growth for biomedical research in Kansas and beyond.