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High-probability grants
According to our matching algorithm, Kara L. Marshall is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2019 — 2020 |
Marshall, Kara L |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Molecular Mechanisms of Stomach Stretch Sensing @ Scripps Research Institute
Project Summary Unlike sight, taste and smell, mechanical senses extend beyond a single sensory organ, and encompass processes as diverse as hearing, touch, and interoception. Despite their physiological importance, the molecular identity of mechanotransduction channels has been mostly unknown. Our lab discovered the first vertebrate mechanically gated cation channels, PIEZO1 & 2, which are critical for many aspects of mechanosensation. We have shown that PIEZO2 plays a critical role in detecting touch, proprioception and lung stretch. Whether PIEZO ion channels play important roles in other forms of internal-organ mechanotransduction is not known. Stretch sensing in the stomach is known to contribute to satiety and downstream digestion processes, yet the molecular identity of stomach stretch sensors is unknown. Preliminary data suggests that stomach stretch-sensing neurons express PIEZO ion channels. This proposal will determine how PIEZO ion channels contribute to stomach mechanosensing, and importantly, define how stretch signals from the stomach impact feeding behavior and downstream physiology. Interoceptive processes rely on monitoring a combination of chemical and mechanical stimuli. Parsing the precise role of mechanotransduction in these systems is difficult without a molecular handle. For example, the role of mechanosensation in breathing was not defined until PIEZO2 deficiency was analyzed. The exact contribution of mechanical signals to eating is undefined and similarly complicated, but could have important consequences for understanding feeding circuits, weight gain, and metabolic disease. This is the first step to enable the study of how mechanical forces are encoded in the CNS to impact diverse physiological systems.
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1 |
2021 |
Marshall, Kara L |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. |
Molecular Mechanisms of Mechanosensing in the Urinary Tract @ Scripps Research Institute
Project Summary Problems with function in the lower urinary tract (LUT) are remarkably common: in adults over 40, up to 70% of all survey respondents report LUT pathologies. This is in part because the physiology of urination (micturition) is complex: it requires smooth muscle in the bladder and urethra to be coordinated with activity in the voluntary, striated muscle of the urethral sphincter. Seven peripheral reflexes enable this coordination, and all of these arise from mechanical cues in the bladder (i.e. bladder stretch) or in the urethra (i.e. urethral fluid flow or distension). Remarkably, we do not know the identity of the molecules or exactly which cell types sense these mechanical forces. For example, two cell types, sensory neurons that innervate the LUT and the urothelial cells in the bladder, are proposed to contribute to these reflexes. Therefore, the details of how these reflexes are initiated and integrated in the system remain poorly understood. I hypothesize that the mechanosensory ion channels PIEZO1 and PIEZO2 mediate mechanosensing in the lower urinary tract. I will use bladder-pressure recordings in combination with electromyography to characterize micturition reflexes, as well as histology and behavior to characterize the expression and the functional role of PIEZOs in urination, specifically as they function in the urothelial cells. I will also test the role of PIEZOs in mediating bladder accommodation responses to fluid filling, as well as their role in mediating pain during pathological conditions like cystitis. Together, these results will delineate the contribution of the mechanotransduction ion channels, specific cell types and peripheral circuitry that facilitate urination. Understanding these processes is an important first step to alleviate the enormous burden of LUT pathologies in humans.
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