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Role of alveolar epithelial cell-derived cellular communication network factor 2 (CCN2) in alveologenesis and bronchopulmonary dysplasia

Award Number: K08HL151760
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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PROJECT SUMMARY/ABSTRACT This proposal describes a 5-year training program to provide Dr. Deepthi Alapati, MD, MS, Attending Neonatologist at Nemours AI duPont Hospital for Children with the mentorship, training and research experience required to become an independent clinician scientist and a leader in neonatal lung disease research. She has received a Master’s degree in Translational Research from University of Pennsylvania. Candidate’s long-term career goal is to develop novel therapies to promote lung repair and regeneration for treatment of neonatal lung diseases such as bronchopulmonary dysplasia (BPD). To achieve these goals, she will be mentored by a team of internationally recognized experts in pulmonary basic science research from Nemours and University of Pennsylvania with whom she has a proven track record of successful mentorship and productivity. She will undergo a rigorous didactics and hands-on training program to acquire expertise in elucidating pulmonary cell-specific molecular mechanisms within the lung microenvironment using complex genetic mouse models and 3D co-culture systems; application of gene editing technologies as a mechanistic and therapeutic tool to modulate candidate genes in complex lung diseases such as BPD; and expertise in advanced bioinformatics. Her research will focus on (1) elucidating the function of Cellular communication network factor 2 (Ccn2) in alveolar epithelial cells (AEC) during alveologenesis and (2) evaluating whether modulating Ccn2 expression in AEC will improve a hyperoxia-induced BPD phenotype. This research proposal is built upon candidate’s preliminary research that demonstrates an important causative role for Ccn2 in severe BPD and the therapeutic potential of CRISPR-Cas9 gene editing technology to manipulate disease causing genes expressed in the developing pulmonary epithelium. BPD is the most common cause of death, severe neurodevelopmental impairment, and hospital readmissions in preterm infants. In spite of advances in clinical care, clinical efforts to prevent and treat BPD have been largely unsuccessful. As the cell type most exposed to the external environment, AEC have emerged as a central focus in many lung diseases, including BPD. Moreover, AEC can be directly targeted by therapeutic agents delivered through intra-amniotic, intra-nasal and intra-tracheal routes. Thus, a better understanding of mechanisms in AEC that drive alveologenesis during normal lung development and in response to early postnatal lung injury, would pave path for targeted therapies for severe BPD. By precisely examining the spatial and temporal function of Ccn2 in AEC during alveologenesis and early postnatal lung injury induced by hyperoxia, this study will provide novel mechanistic insights into its role in regulating alveologenesis and lead to novel therapies targeted at AEC-derived Ccn2 for the prevention and treatment of severe BPD. Candidate has access to all required technical, laboratory and intellectual resources in an ideal collaborative environment for successfully conducting her research and pave the path to develop as an independent investigator.


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: 2023 ( Subtotal = $162,000 )
2023	2023	THE NEMOURS FOUNDATION	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Lung Diseases Research	000	4	8/9/2023	NON-COMPETING CONTINUATION	$162,000
														Subtotal = $162,000

Issue Date FY: 2022 ( Subtotal = $162,000 )
2022	2022	NEMOURS FOUNDATION, THE	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Lung Diseases Research	001	3	8/16/2022	NON-COMPETING CONTINUATION	$162,000
2022	2021	NEMOURS FOUNDATION, THE	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Lung Diseases Research	000	2	3/11/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $162,000

Issue Date FY: 2021 ( Subtotal = $162,000 )
2021	2021	NEMOURS FOUNDATION, THE	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Lung Diseases Research	000	2	7/30/2021	NON-COMPETING CONTINUATION	$162,000
														Subtotal = $162,000

Issue Date FY: 2020 ( Subtotal = $162,000 )
2020	2020	NEMOURS FOUNDATION, THE	1600 ROCKLAND RD	WILMINGTON	DE	19803	NEW CASTLE	USA	Lung Diseases Research	000	1	7/10/2020	NEW	$162,000
														Subtotal = $162,000

Grand Total All Awards = $648,000

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Role of alveolar epithelial cell-derived cellular communication network factor 2 (CCN2) in alveologenesis and bronchopulmonary dysplasia

Award Number: K08HL151760

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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