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The molecular and genetic bases of diverse tissue repair responses in postembryonic Drosophila

Award Number: R35GM126929
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: 04/01/2018
PERIOD OF PERFORMANCE END DATE: 04/02/2026
AWARD TERMINATION DATE: 03/18/2026

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The molecular and genetic bases of diverse tissue repair responses in postembryonic Drosophila - Tissue damage responses are essential for multicellular organisms that occasionally encounter a hostile environment. These multi-tissue responses include epithelial barrier repair (wound healing), inflammation, and sensory responses like nociceptive sensitization. Together, these coordinated responses restore tissue functionality and/or protect the tissue from further damage while it heals. Our overarching hypothesis is that the biology of tissue repair arose early in the evolution of multicellular organisms. Consequently, many of the cellular strategies, signaling pathways, and behaviors that animals use to sense and to repair damage are ancient and evolutionarily conserved. Discovery of the basic cell biology and genetic underpinnings of these damage-induced responses is essential. Our long term goal is to identify the full suite of cells and genes that initiate and execute each tissue damage response and understand how these cells and genes function and work together to orchestrate successful repair of damaged tissues. My laboratory has pioneered the use of Drosophila larvae to study postembryonic tissue damage responses including wound closure, inflammation, and injury-induced nociceptive (pain) sensitization. During our first four years of MIRA funding we discovered important principles of wound edge adhesion dynamics, found a signaling pathway (related to vertebrate Vascular Endothelial Growth Factor [VEGF] signaling) required for spreading of inflammatory blood cells at wound sites, and explored injury-induced sensitization to cold, chemical, and mechanical stimuli. Our work over the next five years will focus on three key questions that emerge naturally from these prior studies: 1. How are adherens junction proteins (like β-Catenin) removed from the wound edge and how does this removal impact other wound-edge responses like actin polymerization? This question emerges from our observation that β-Catenin is rapidly removed from wound-edge membranes. With new tools we developed in the prior grant period we are in an excellent position to image this process in real-time at highly symmetric wounds and to discover which signaling pathways coordinate removal. 2. One key question with respect to inflammation is how inflammatory blood cells initially adhere to the wound. In our second project we will explore this key question and investigate the relationship between immune cell adhesion/spreading and immune cell function at the wound site. Our final project will seek to identify key functional downstream genes that mediate acute injury-induced nociceptive sensitization. This is a major gap in our understanding of this process and a key question in the study of nociceptive sensitization. My lab’s substantial history of creative high-impact research on diverse tissue damage responses suggests strongly that we will continue to make original strides and discoveries, especially if our ongoing grant-writing burden is lessened through the MIRA mechanism. Our system complements others in the field and the likelihood of continued novel basic insight into how organisms cope with tissue damage at the cellular and molecular/genetic levels is high.


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	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	8	3/18/2026	TERMINATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $421,200 )
2025	2025	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	002	8	6/17/2025	NON-COMPETING CONTINUATION	$421,200
2025	2024	THE UNIVERISTY OF TEXAS MD ANDERSON CANCER CENTER, A COMPONENT OF THE UNIVERISTY OF TEXAS SYSTEM	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	7	11/6/2024	NON-COMPETING CONTINUATION	$0
2025	2022	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	001	5	1/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $421,200

Issue Date FY: 2024 ( Subtotal = $421,200 )
2024	2024	THE UNIVERISTY OF TEXAS MD ANDERSON CANCER CENTER, A COMPONENT OF THE UNIVERISTY OF TEXAS SYSTEM	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	7	6/27/2024	NON-COMPETING CONTINUATION	$421,200
														Subtotal = $421,200

Issue Date FY: 2023 ( Subtotal = $421,200 )
2023	2023	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	001	6	7/31/2023	COMPETING CONTINUATION	$421,200
2023	2022	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	5	7/30/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $421,200

Issue Date FY: 2022 ( Subtotal = $400,000 )
2022	2022	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	001	5	6/27/2022	NON-COMPETING CONTINUATION	$40,002
2022	2022	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	5	3/18/2022	NON-COMPETING CONTINUATION	$359,998
														Subtotal = $400,000

Issue Date FY: 2021 ( Subtotal = $400,000 )
2021	2021	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	4	3/16/2021	NON-COMPETING CONTINUATION	$400,000
														Subtotal = $400,000

Issue Date FY: 2020 ( Subtotal = $400,000 )
2020	2020	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	3	3/4/2020	NON-COMPETING CONTINUATION	$400,000
														Subtotal = $400,000

Issue Date FY: 2019 ( Subtotal = $540,056 )
2019	2019	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	2	3/8/2019	NON-COMPETING CONTINUATION	$400,000
2019	2019	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	001	2	6/5/2019	SUPPLEMENT FOR EXPANSION	$140,056
														Subtotal = $540,056

Issue Date FY: 2018 ( Subtotal = $377,429 )
2018	2018	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	000	1	3/22/2018	NEW	$377,429
														Subtotal = $377,429

Grand Total All Awards = $3,381,085

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The molecular and genetic bases of diverse tissue repair responses in postembryonic Drosophila

Award Number: R35GM126929

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: 04/01/2018

PERIOD OF PERFORMANCE END DATE: 04/02/2026

AWARD TERMINATION DATE: 03/18/2026

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