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Roles of mechanotransduction in organ regeneration and fibrosis

Award Number: R35GM142504
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Roles of mechanotransduction in organ regeneration and fibrosis - Project Summary Environmental biomechanical cues play a critical role in cell growth and functional homeostasis. Many human diseases, such as organ fibrosis, cardiovascular diseases, and cancers, have been associated with aberrant biomechanical cues that promote disease progression. However, how cells sense and propagate biomechanical cues into biochemical signals, a process known as mechanotransduction, is poorly understood. In particular, the precise signaling transduction mechanisms and transcriptional outputs of mechanotransduction remain unknown. Unveiling the roles and signaling cascades of mechanotransduction is important for understanding fundamental development and disease mechanisms and for advancing therapeutic strategies. I have been developing a research program to elucidate the roles and mechanisms of mechanotransduction in tissue growth control and disease development, with a current focus on how mechanotransduction controls regeneration and fibrosis during organ injury and repair. The main challenge in understanding mechanotransduction in this disease context is the lack of knowledge of mechanotranscriptomes and signaling cascades that are triggered by a combination of force-, cell-, and microenvironment-specific factors. In this proposal, I aim to answer 3 main questions to advance our understanding in the field: (i) what role does mechanotransduction play in regulating cellular functions and transcriptomes, particularly in the context of tissue repair? (ii) what are the signaling cascades that connect plasma membrane mechanosensors to mechanotranscriptomes? (iii) how do biomechanical cues and wound-healing signals integrate to control cellular functions and transcriptomes? I will use endothelial cells and the liver as my main models to study these questions, as they are classical models for studying mechanotransduction and tissue repair, respectively. We will characterize endothelial mechanotransduction for its roles in liver regeneration and fibrosis mainly using (i) in vitro or ex vivo bioengineered models with human primary endothelial cells, and (ii) in vivo mouse models of liver injury. My research program will also include similar studies of fibroblast mechanotransduction and lung regeneration and fibrosis. I anticipate that my research program will advance the fundamental understanding of mechanotransduction in normal and diseased contexts, providing opportunities for identifying new druggable targets from mechano-signaling cascades for organ fibrosis and other diseases with aberrant tissue mechanics.


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: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Biomedical Research and Research Training	000	5	2/9/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $383,750 )
2025	2025	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Biomedical Research and Research Training	000	5	4/29/2025	NON-COMPETING CONTINUATION	$383,750
														Subtotal = $383,750

Issue Date FY: 2024 ( Subtotal = $383,750 )
2024	2024	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Biomedical Research and Research Training	000	4	6/13/2024	NON-COMPETING CONTINUATION	$383,750
														Subtotal = $383,750

Issue Date FY: 2023 ( Subtotal = $482,930 )
2023	2023	UNIVERSITY OF MIAMI	1400 NW 10TH AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	3	3/27/2023	NON-COMPETING CONTINUATION	$383,750
2023	2023	UNIVERSITY OF MIAMI	1400 NW 10TH AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	001	3	5/19/2023	SUPPLEMENT FOR EXPANSION	$99,180
														Subtotal = $482,930

Issue Date FY: 2022 ( Subtotal = $383,750 )
2022	2022	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	001	2	6/22/2022	NON-COMPETING CONTINUATION	$38,375
2022	2022	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	2	4/11/2022	NON-COMPETING CONTINUATION	$345,375
														Subtotal = $383,750

Issue Date FY: 2021 ( Subtotal = $383,750 )
2021	2021	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	1	6/28/2021	NEW	$383,750
														Subtotal = $383,750

Grand Total All Awards = $2,017,930

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Roles of mechanotransduction in organ regeneration and fibrosis

Award Number: R35GM142504

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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