Regulating parenchymal repair in wound healing
Active Project Grant Awarded Last action
- Award ID
- R35GM154942
- Recipient
-
Trustees Of Boston University UEI THL6A6JLE1S7
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,650,000
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 48% complete
- Place of performance
- Boston, MA 02215, USA
Award details come from USAspending.gov.
Description
- Abstract
- Many tissues in adult mammals are incapable of regeneration after injury because the parenchymal cells that provide the specialized tissue functions lack sufficient self-renewal capacity. When parenchymal cells cannot facilitate tissue regeneration, non-functional fibrotic scarring occurs. In the select tissues that can regenerate, such as the liver, resident parenchymal cells enter states of high self-renewal upon injury to enable parenchymal repair and recovery of organ function. Mammalian neonates have parenchymal repair capacity in most tissues too because newborn immature parenchymal cells maintain elevated levels of self- renewal, but these cells rapidly become quiescent during postnatal development and lose repair competency. Based on these insights, an important question remains as to whether parenchymal repair can be induced in adult tissue injuries simply by enhancing the self-renewal capacity of certain adult parenchymal cells. Addressing the significant gaps in our understanding of the mechanisms that are responsible for limiting the injury-induced self-renewal in adult parenchymal cells will be required to answer this question. Thus, this project is focused on dissecting molecular mechanisms responsible for self-renewal deficiencies in adult parenchymal cells following injury and testing strategies for improving adult wound healing outcomes by regulating these processes. We will address fundamental knowledge gaps in parenchymal repair using the mouse central nervous system (CNS) as a model organ system and focus on one important quiescent parenchymal cell population in the CNS, astrocytes, for detailed study. As part of this work, we will explore 3 separate but complementary initiatives and use an experimental toolkit of modular biomaterials, in vitro astrocyte cultures, and mouse spinal cord injury models. In initiative 1, we will dissect the mitotic and anti- mitotic growth factor signaling that regulates parenchymal repair and we will incorporate injectable biomaterial coacervates to precisely deliver molecular regulators of this signaling in vivo. In initiative 2, we will identify metabolic fuels necessary for sustaining parenchymal cell self-renewal after injury and use injectable glyco-nucleoside copolymer hydrogels to permit prolonged delivery of optimized metabolic fuels to injury lesions. In initiative 3, we will dissect non-cell autonomous regulation of parenchymal cell self-renewal by recruited lesion cells by using injectable biomaterials to locally dysregulate these natural injury-induced cell- cell interactions. Collectively, the three initiatives will shed new light on the molecular requirements for enhancing parenchymal repair in adult tissue injury and will transform our understanding of wound healing that will be applicable to many organ systems.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $412,500 | |
| Amendment | $412,500 | |
| Amendment | $412,500 | |
| Original award | $412,500 |
Quick answers
Who received award R35GM154942?
R35GM154942 was awarded to Trustees Of Boston University by National Institute of General Medical Sciences (National Institutes of Health) on July 1, 2024.
How much is award R35GM154942 worth?
$1,650,000 has been obligated on R35GM154942.
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