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Functional Categorization of Ciliary Motion in PCD

Award Number: K08HL138153
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/07/2019
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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Functional Categorization of Ciliary Motion in PCD - PI: Solomon, George M. Primary Ciliary Dyskinesia (PCD) is a genetically heterogeneous disorder of motile cilia that results in progressive lung disease due to abrogated mucociliary clearance. While new understandings of the genetics have been helpful for clinical diagnostics, functional testing of cilia are needed to understand and predict phenotypic variation and response to therapy. Recent work in our laboratory has identified a link between ciliary genetics and novel ciliary phenotypes using one-micron optical coherence tomography (µOCT). We have phenotyped the ciliary beating pattern of known and novel murine PCD models. We have extended this work to humans through the use of human nasal epithelial cells. Using these technologies, we will characterize and quantify functional ciliopathies My overall hypothesis is that PCD mutations can be functionally analyzed to diagnose PCD, understand genotype-phenotype correlation on a mechanistic level, and predict clinical response to ciliary agonists. The goals of this proposal are 1) to advance μOCT and other functional imaging analysis to diagnose and categorize the functional consequences of PCD-associated gene defects on Mucociliary transport in primary human cells and 2) determine whether pharmacological modulation of ciliary function can augment ciliary motility and mucus clearance in mutants with motile cilia expression through the following specific aims: Specific Aim 1: Determine the diagnostic accuracy of µOCT-based functional analysis of primary human airway cells. Specific Aim 2: Determine the relationship between genotype and functional ciliary phenotype in PCD. Specific Aim 3: Determine whether pharmacologic modulation of CBF can rescue MCT in PCD with motile cilia expression. This project explores new concepts in the pathobiology of primary ciliary dyskinesia through the innovative use of in vitro imaging (µOCT) measures of mucociliary transport and ciliary motion to diagnose and precisely phenotype clinical PCD and the effect of genetics on ciliary function and MCT in human tissues. In so doing, we will establish a protocol for testing of treatments to augment MCT and ciliary function. The accompanying career development plan and the research aims as outlined above are of equal importance in the development of this project. Combined with a strong mentoring committee, additional training in genetics and cardiopulmonary physiology, study design, methodology, and statistical analysis, Dr. Solomon will have all the tools to achieve his career goal as an independent physician-scientist. The opportunities created by this career development award will result in the creation of a physician-scientist with the skills necessary to accurately and ethically answer important scientific questions about potential therapies for PCD phenotypes, successfully obtain future independent funding, and make important differences in the lives of PCD patients


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$160,089 )
2024	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	001	5	4/23/2024	NON-COMPETING CONTINUATION	-$159,882
2024	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH STREET	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	4	4/23/2024	NON-COMPETING CONTINUATION	-$207
														Subtotal = -$160,089

Issue Date FY: 2023 ( Subtotal = $159,882 )
2023	2023	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	5	12/16/2022	NON-COMPETING CONTINUATION	$159,882
														Subtotal = $159,882

Issue Date FY: 2022 ( Subtotal = $159,882 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	4	12/31/2021	NON-COMPETING CONTINUATION	$159,882
														Subtotal = $159,882

Issue Date FY: 2021 ( Subtotal = $159,882 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	3	12/31/2020	NON-COMPETING CONTINUATION	$159,882
														Subtotal = $159,882

Issue Date FY: 2020 ( Subtotal = $159,882 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	2	12/31/2019	NON-COMPETING CONTINUATION	$159,882
														Subtotal = $159,882

Issue Date FY: 2019 ( Subtotal = $159,882 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Lung Diseases Research	000	1	1/3/2019	NEW	$159,882
														Subtotal = $159,882

Grand Total All Awards = $639,321

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Functional Categorization of Ciliary Motion in PCD

Award Number: K08HL138153

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/07/2019

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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