[K08] Smooth Muscle Mechanotransduction: Calcium Dynamics in the Developing Gut
Ente: National Institute of Diabetes and Digestive and Kidney Diseases
Scadenza: 2030-06-30
Importo max: 164.700 EUR
Paese: US
Descrizione
PROJECT SUMMARY/ABSTRACT
This NIH Mentored Clinician Scientist Development (K08) proposal describes a comprehensive 5-
year training plan designed to establish Geoanna Bautista, M.D. as an independent physician-
scientist focused on mechanosensitive signaling pathways that contribute to neonatal intestinal
dysmotility. Prematurity is the leading cause of death and disability in infants in the United States,
and intestinal dysmotility resulting from an immature GI system is a significant yet understudied
complication. Yet, no effective therapies address prematurity-related intestinal dysmotility due to
critical knowledge gaps in understanding the development of GI motility.
To address this foundational gap, Dr. Bautista will investigate mechanosensitive regulation driving
intestinal maturation, which is important for establishing normal GI motility. Based on strong
preliminary data supporting a critical role of the mechanosensitive ion channel, Piezo1, in normal
intestinal motility and development, Dr. Bautista will test the hypothesis that Piezo1 is
developmentally regulated and has a distinct role in the modulation of SMC Ca2+ activity during
intestinal maturation. She will employ her previously established conditional knockout murine model
to selectively deplete Piezo1 in SMCs during the neonatal period, combined with cutting-edge
techniques such as super-resolution microscopy, live single cell and in situ Ca2+ imaging with and
without stretch, to rigorously test this hypothesis. Specifically, in Aim 1, she will define the precise
distribution and role of Piezo1 activation in SMCs of the developing intestine, and in Aim 2, she will
determine the developmental consequences of Piezo1-deficient SMCs for intestinal contractility.
The data to be obtained will provide new knowledge and mechanistic insights into the mechanical
regulation of SMC [Ca2+]i signaling during intestinal development. More importantly, Dr. Bautista
will gain training from the pioneering expertise of her diverse mentorship team in an excellent
scientific environment. Dr. Bautista’s long term goals are to: 1) lead and perform rigorous
mechanistic research to test clinically relevant models of intestinal mechanobiology during gut
development, and 2) utilize these findings to explore innovative therapeutic strategies to address
the burden of intestinal dysmotility in neonates. These goals will form the foundation of her
independent research program, aligning closely with the NIDDK’s strategic plan and overall mission.
Istituzione: UNIVERSITY OF CALIFORNIA AT DAVIS
PI: Geoanna Marie Bautista
Progetto: 5K08DK143334-02
Settori: National Institute of Diabetes and Digestive and Kidney Diseases
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