Friday, May 9, 2025
5/9/2025
Mechanosensing and calcium signaling in epithelial cells drives allergic response to protease allergen - PROJECT SUMMARY/ABSTRACT This proposal outlines a career development and research plan for Dr. Darin L Wiesner to transition from his postdoctoral fellowship into an independent academic faculty position, where he will investigate asthma. Candidate: Thus far, I have focused my scientific career on unravelling immunopathologies caused by T cells. This interest began during my time as a technician when I was involved in a project that examined a deadly immune disease experienced by persons living with AIDS. In graduate school, I tilted my research interests towards understanding the priming and suppression of detrimental T cell responses to invasive pulmonary fungal infection. I am currently immersed in a project that aims to understand how lung epithelial cells recognize and respond to protease allergen and instigate T cell-dependent allergic inflammation. Career development plan: During the remaining time as a postdoctoral fellow, I will work closely with my current mentor to develop abilities that will be necessary after I am an independent investigator, such as: management, finances, and writing protocols. I will also leverage resources available at UW Postdoc Association, National Research Mentoring Network, and UW Delta Program to help navigate the job search. Upon starting an assistant professorship, I will prioritize finding a mentor at the hiring university that can help me navigate the local landscape and provide critical guidance in areas, like: faculty commitments, institutional funding sources, and pre-tenure progress. Collectively, this approach will refine my scientific skill set, identify a University/Department that is a good fit, and be in a position to succeed in my independent academic career. Research project: The overarching goal of the scientific portion of the proposal is to better understand the involvement of epithelial club cells during initial sensitization of allergic asthma. I have generated sound preliminary data that supports the premise that bronchiolar club cells respond to inhaled protease by sensing junction damage via TRPV4, fluxing calcium, and signaling inflammation. Therefore, I will explore mechanotransduction and calcineurin-dependent transcription factors that form a complete signaling pathway during allergic sensitization. These studies will support a paradigm shift in how living cells sense danger. Moreover, a more solidified understanding of club cell intrinsic signaling pathways will yield information about the products that emanate from club cells to assemble the allergic response. Collectively, this will pave the way for future grant proposals to study danger pathways in other diseases systems, as well as novel immunologic circuits downstream of club cells involved in asthma.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).