BRC-BIO: The role of the Sphingosine 1-Phosphate and Cyclooxygenase-2 pathway in the crosstalk between fibrosis and angiogenesis

James Madison University, Harrisonburg VA

Investigators

Abstract

The mechanisms regulating tissue repair and regeneration are complex and not fully understood. After injury, scar formation often occurs. Scar tissue is non-functional and formed as an abnormal response to tissue repair. At the same time, one of the needed processes occurring during tissue repair is the formation of new blood vessels, which is known as angiogenesis. This research will establish the molecular mechanisms involving scar formation and angiogenesis after injury, using different human cell culture systems combined with various molecular and imaging techniques. Undergraduate and graduate students as well as a post-baccalaureate research associate will be mentored and trained in the scope of this research, which will include research training in technical skills, data analysis and interpretation, science communication, and professional development. In addition, research will be disseminated by teaching undergraduates at James Madison University and through a cellular and molecular biology hands-on workshop to local students in grades 6-8. This research will contribute to elucidating the molecular mechanisms modulating scar formation and angiogenesis after injury, while equipping students and the research associate with skills to be competitive in a constantly evolving STEM workforce. Fibrosis is an abnormal response to tissue repair resulting in the excessive creation and deposition of extracellular matrix to form scar tissue. Simultaneously, angiogenesis is a multistep and tightly regulated process characterized by the growth of new capillaries from existing blood vessels and plays an essential role in tissue regeneration. The Sphingosine 1-Phosphate (S1P) and Cyclooxygenase-2 (COX-2) pathways are activated during tissue regeneration, but the role of crosstalk between tissue repair and regeneration pathways that form fibrotic scar tissue and stimulate angiogenesis is still largely unknown. The proposed research will establish the molecular basis for the crosstalk between fibrosis and angiogenesis after injury by use of a combination of in vitro human cell culture and co-culture systems. The PIs will focus efforts on the S1P-COX-2 pathway, which is hypothesized to be a common pathway linking the processes of fibrosis and angiogenesis after injury. This research will advance the fundamental knowledge of critical tissue repair and regeneration processes, providing a deeper understanding of the interactions between molecular pathways modulated after injury. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.