NCI Division of Cancer Biology Junior Investigators Meeting (Abstract): Submission #3

Presenter Information
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First Name: Isha
Middle Initial: {Empty}
Last Name: Bhorkar
Degree(s): M.S.
Position/Title/Career Status: Graduate Student
Organization: University of Michigan
Organization Address:
Ann Arbor, MI

Email: ibhorkar@umich.edu

Abstract Information
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Abstract Category: Consider my abstract for a Methodology/Technology presentation
Abstract Keywords: Mechanobiology, Shear stress, Microfluidics, Organoids
Abstract Title: Multiscale Approaches for Studying Fluid Shear Stress and Mechanoadaptation in Human Fallopian Tube Epithelium
Abstract:
The fallopian tube (FT) epithelium is the tissue of origin for most high-grade serous ovarian carcinoma (HGSOC). FT epithelial cells are continuously exposed to fluid shear from follicular fluid release, peristaltic contractions, and ciliary beating, yet how this mechanical environment shapes epithelial behavior and early transformation risk remains poorly understood. My research addresses this gap by combining computational modeling of luminal fluid mechanics with experimental mechanosensing studies in patient-derived microfluidic models.
To characterize the physical environment, I use NanoCT imaging and a custom Python pipeline (skeletonization, perpendicular plane resampling, hydraulic diameter calculation) to reconstruct patient-specific FT luminal geometry and estimate physiological wall shear stress, capturing how mucosal folding shapes the flow environment. These geometric models also feed into computational simulations to generate patient-informed shear estimates.
To link this biomechanical context to cellular response, cells from patient FT organoids are exposed to calibrated, physiological shear stress in microfluidic devices, alongside immortalized comparator lines that provide a transformed counterpart to normal FT epithelium. Cellular responses are characterized through RNA sequencing, live calcium imaging with pharmacological modulation of mechanosensitive channels, and immunofluorescence-based quantification of cytoskeletal organization and epithelial morphology. A perfused, membrane-based device extends this workflow to resolve mechanosensing across ciliated and secretory cell populations.
This work has given me hands-on expertise in patient-derived organoid culture, microfluidic device design and fabrication, quantitative image analysis, and the integration of structural, computational, and transcriptomic data. This biophysical and quantitative perspective could contribute to collaborative projects that connect tissue mechanics, tissue architecture, and mechanosensing to early cancer risk, detection, or progression across tissue types.