Friday, June 20, 2025 6/20/2025

New upstream targets for HIF-1a-mediated regeneration in young and aged animals

Award Number: R01DE021104
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2011
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

New upstream targets for HIF-1a-mediated regeneration in young and aged animals - Project Summary/Abstract The ability to regenerate tissue in mammals has remained elusive. While the use of stem cell populations in the context of bio-scaffolds has shown promise as a potential means of replacing lost, damaged, or diseased tissue, significant challenges remain. An alternative approach is to attempt to evoke a classical in situ regenerative response emulating that seen in lower species such as newts. While this trait was thought to be lost in evolution, our observation (Heber-Katz) that the MRL mouse and related strains have a significant spontaneous regenerative capability demonstrates that the trait is retained in mammals. Studies over the past almost 25 years have culminated in the identification of the HIF-1α (hypoxia inducible factor) pathway as the central actor regulating regeneration in mice. The up-regulation of HIF-1α in non-regenerating mice have allowed these mice to regenerate ear holes with cartilage and hair follicles; and jaw bone and associated soft tissues after induced periodontal disease (PD). In both cases, a classical regenerative de-differentiation response was seen. This was achieved using the PHD inhibitor 1,4-DPCA in novel injectable biomaterial constructs (Messersmith) leading to the stabilization of high levels of HIF-1α in vivo. The mechanisms that were identified in the PD model involved inflammatory cytokines, bone remodeling osteoblasts, Tregs and CXCR4 expression. Using a CXCR antagonist, AMD3100, the regenerative response could be blocked and supports the need for Tregs and certain stem and myeloid cells. In this current proposal, we provide preliminary results showing that two new upstream target molecules DEL-1 (Hajishengallis) and PAR1 (Heber-Katz) with known agonists have been identified which affect HIF-1α expression. We will explore the role of HIF-1α and these two molecules in the regenerative response in young and aged mice using both the ear hole model and the PD model. We will use advanced molecular design to produce a biomaterial capable of achieving single dose and local delivery vs the current three dose delivery system. In addition to yielding a novel soft and bone tissue regeneration therapy, we believe that this system provides an impressive landscape of phenomena that will yield important mechanistic information about in-situ regenerative responses in oral tissues. In Aim 1, we will create new biomaterials to yield local drug release using mucoadhesive polymers; in Aim 2, we will examine the role of the anti-inflammatory molecular DEL-1 in aged mice with PD, a molecule having direct affects on HIF-1α levels; and in Aim 3, we will examine the role of PAR1, another molecule which affects HIF-1α levels in the ear hole and periodontal injury models, in both young and aged mice.


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: 2025 ( Subtotal = $693,701 )
2025	2025	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	14	5/8/2025	NON-COMPETING CONTINUATION	$693,701
														Subtotal = $693,701

Issue Date FY: 2024 ( Subtotal = $689,417 )
2024	2024	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	13	5/31/2024	NON-COMPETING CONTINUATION	$689,417
2024	2021	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	001	11	9/27/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $689,417

Issue Date FY: 2023 ( Subtotal = $766,184 )
2023	2023	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	001	12	7/20/2023	COMPETING CONTINUATION	$35,130
2023	2023	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	12	7/12/2023	COMPETING CONTINUATION	$731,054
														Subtotal = $766,184

Issue Date FY: 2021 ( Subtotal = $705,109 )
2021	2021	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	11	8/13/2021	NON-COMPETING CONTINUATION	$705,109
														Subtotal = $705,109

Issue Date FY: 2020 ( Subtotal = $705,109 )
2020	2020	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	10	8/6/2020	NON-COMPETING CONTINUATION	$705,109
														Subtotal = $705,109

Issue Date FY: 2019 ( Subtotal = $705,109 )
2019	2019	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	9	7/24/2019	NON-COMPETING CONTINUATION	$705,109
														Subtotal = $705,109

Issue Date FY: 2018 ( Subtotal = $705,109 )
2018	2018	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	8	8/9/2018	NON-COMPETING CONTINUATION	$705,109
														Subtotal = $705,109

Issue Date FY: 2017 ( Subtotal = $737,609 )
2017	2017	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	7	9/7/2017	COMPETING CONTINUATION	$737,609
2017	2015	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 E LANCASTER AVE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	001	6	9/19/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $737,609

Issue Date FY: 2015 ( Subtotal = $410,502 )
2015	2015	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 LANCASTER AVENUE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	002	6	4/3/2015	NON-COMPETING CONTINUATION	$410,502
2015	2014	LANKENAU INSTITUTE FOR MEDICAL RESEARCH	100 LANCASTER AVENUE	WYNNEWOOD	PA	19096	MONTGOMERY	USA	Oral Diseases and Disorders Research	000	5	2/9/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$235,300
2015	2014	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	001	4	2/9/2015	NON-COMPETING CONTINUATION	-$235,300
														Subtotal = $410,502

Issue Date FY: 2014 ( Subtotal = $443,210 )
2014	2014	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	4	4/16/2014	NON-COMPETING CONTINUATION	$443,210
														Subtotal = $443,210

Issue Date FY: 2013 ( Subtotal = $405,468 )
2013	2013	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	3	4/29/2013	NON-COMPETING CONTINUATION	$380,129
2013	2013	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	001	3	5/13/2013	NON-COMPETING CONTINUATION	$25,339
														Subtotal = $405,468

Issue Date FY: 2012 ( Subtotal = $427,798 )
2012	2012	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	2	4/5/2012	NON-COMPETING CONTINUATION	$427,798
														Subtotal = $427,798

Issue Date FY: 2011 ( Subtotal = $437,674 )
2011	2011	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	1	4/15/2011	NEW	$437,674
														Subtotal = $437,674

Grand Total All Awards = $7,831,999

Top

All Categories

About

Search

Reports

Data Submission

Award Information

New upstream targets for HIF-1a-mediated regeneration in young and aged animals

Award Number: R01DE021104

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2011

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer