# Administrative Supplement for the Study of Shear Stress in Uterine Serous Carcinoma > **NIH NIH R37** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $155,446 ## Abstract Project Summary This application is being submitted in response to the Notice of Special Interest (NOSI) identified as “NOT-CA- 24-044. Uterine serous carcinoma (USC) represents a challenging women’s health concern, with over 30% of patients diagnosed alongside peritoneal ascites, a marker of the disease's progression. This subtype of endometrial cancer is notorious for its robust resistance to conventional treatments, a tendency for pelvic recurrence, and a diminished likelihood of long-term survival. USC cells are often found in detached, papillary clusters and commonly lead to the development of both ascites and pleural effusions. Interestingly, within such environments, mechanical forces—shear, viscosity, compression, and tension —exert dynamic influences on the evolution of these cancer cells. Our investigation seeks to delineate the impact of shear stress within the fluid occupied by ascites and pleural effusions in USC. Leveraging techniques established through our research into the roles of shear stress in high-grade serous ovarian and triple-negative breast cancers, we aim to determine the molecular underpinnings of mechanotransduction in USC. Our objective is clear - to unlock advanced treatment strategies tailored to combat both newly diagnosed and recurrent USC. Our hypothesis posits that ascites-induced shear stress activates epithelial-to-mesenchymal transition in USC, accelerating metastatic disease. Our interdisciplinary team merges Dr. DiFeo's deep proficiency in patient- derived USC xenograft models and cell lines, with Dr. Mehta's expertise in shear stress investigations that utilize 3D in vitro models, that are being employed to study transformation of fallopian tube secretory epithelial cells in our parent grant. Through this cutting-edge research, underpinned by supplemental support, we anticipate confirming whether shear stress catalyzes metastasis in USC, marking a significant leap in our understanding of this disease’s progression. Eager to distill the bimolecular consequences of shear stress, we will scrutinize alterations in cellular membrane architecture—including the glycocalyx and ion channels—by comprehensive analysis of patient- derived USC cell lines. Our pursuit will trace the activation of ion channels and G-protein-coupled receptors that respond to shear stress, as suggested by our work in the parent grant. Complementing this, we will employ USC tissue microarrays and spatial transcriptomics to map a shear stress signature from unique cellular responses, creating a nexus of insights when compared with ours’ and those of others’ prior findings on mechanotransduction in cancers. This integrative approach is instrumental in revealing the role of mechanical stimuli in the migration, invasion, and colonization of uterine tumors via ascites, thereby furnishing new frontiers in its treatment innovation. With the potential to significantly enhance the early detection and treatment of USC— especially at its most crucial... ## Key facts - **NIH application ID:** 11129113 - **Project number:** 3R37CA282790-02S1 - **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR - **Principal Investigator:** Geeta Mehta - **Activity code:** R37 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $155,446 - **Award type:** 3 - **Project period:** 2024-09-01 → 2028-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11129113 ## Citation > US National Institutes of Health, RePORTER application 11129113, Administrative Supplement for the Study of Shear Stress in Uterine Serous Carcinoma (3R37CA282790-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11129113. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*