RC2TR005123
Project Grant
Overview
Grant Description
Porcine Related Approach to Multidisciplinary Collaborative Translational Model Research (PROMOTER) - Porcine Related Approach to Multidisciplinary Collaborative Translational Model Research (PROMOTER)
Abstract
Large animal models of human disease are essential to the development, testing, and translation of therapeutics, but fully characterized large animal models of digestive diseases are relatively lacking.
Within this broad digestive disease category, esophageal diseases are an attractive use case, being increasingly prevalent but paradoxically understudied.
There are no approved esophageal-specific drugs or delivery mechanisms, and fundamental questions remain about disease pathogenesis, natural history, outcomes, and individualization of care.
There is a critical need for a large animal model “toolbox” for discovery work enabling rapid translation of knowledge to practice for esophageal diseases.
Because small animal models do not recapitulate human esophageal micro- or macro-structures, are minute in size, and require sacrifice to obtain tissue for examination, progress in many areas of research is hampered.
In contrast, the pig is an ideal esophageal model.
The pig esophagus is analogous in structure and function to the human esophagus, with similar epithelial and sub-epithelial compartments, and motility.
In addition, as the pig and human esophagus are of similar size, the pig model is amenable to endoscopic assessment, enabling both visual inspection and recovery of tissue samples without sacrificing the animal.
This facilitates critical long-term modeling to study disease pathogenesis, progression, and outcomes that are of direct clinical interest.
We have begun to establish the viability of the porcine esophageal approach as a novel resource by exploring injury/repair, the role of stem cells, and drug delivery (with both novel mucosal-targeted formulations and drug-eluting devices), and have created a porcine disease model for eosinophilic esophagitis which demonstrates clear translational potential to human disease.
With our established multidisciplinary team, we propose to use the RC2 mechanism to accelerate discovery and translation to the clinic in esophageal diseases and ultimately in other organs.
Our application has been designed to meet all objectives of the High Impact Specialized Innovation Program, as well as multiple CTSA program goals, with the following specific aims:
1) To generate a comprehensive transcriptional, immunologic, and proteomic profile of the normal porcine esophagus;
2) To develop and generate comprehensive transcriptional, immunologic, and proteomic profiles of porcine models of inflammatory/injury-induced and fibrotic esophageal diseases; and
3) To establish an integrated and self-sustaining center that shares resources with the scientific community to promote translational multidisciplinary research, fundamental hypothesis testing, and therapeutic drug and device development in esophageal diseases, as an initial platform for extension to other human diseases.
This highly innovative and impactful discovery-based and hypothesis-generating research will overcome roadblocks in translational science and enhance activities of the UNC/NC State CTSA UM1 HUB, successfully address a major impediment to translational science, and advance translation of drugs and devices to the clinic.
Abstract
Large animal models of human disease are essential to the development, testing, and translation of therapeutics, but fully characterized large animal models of digestive diseases are relatively lacking.
Within this broad digestive disease category, esophageal diseases are an attractive use case, being increasingly prevalent but paradoxically understudied.
There are no approved esophageal-specific drugs or delivery mechanisms, and fundamental questions remain about disease pathogenesis, natural history, outcomes, and individualization of care.
There is a critical need for a large animal model “toolbox” for discovery work enabling rapid translation of knowledge to practice for esophageal diseases.
Because small animal models do not recapitulate human esophageal micro- or macro-structures, are minute in size, and require sacrifice to obtain tissue for examination, progress in many areas of research is hampered.
In contrast, the pig is an ideal esophageal model.
The pig esophagus is analogous in structure and function to the human esophagus, with similar epithelial and sub-epithelial compartments, and motility.
In addition, as the pig and human esophagus are of similar size, the pig model is amenable to endoscopic assessment, enabling both visual inspection and recovery of tissue samples without sacrificing the animal.
This facilitates critical long-term modeling to study disease pathogenesis, progression, and outcomes that are of direct clinical interest.
We have begun to establish the viability of the porcine esophageal approach as a novel resource by exploring injury/repair, the role of stem cells, and drug delivery (with both novel mucosal-targeted formulations and drug-eluting devices), and have created a porcine disease model for eosinophilic esophagitis which demonstrates clear translational potential to human disease.
With our established multidisciplinary team, we propose to use the RC2 mechanism to accelerate discovery and translation to the clinic in esophageal diseases and ultimately in other organs.
Our application has been designed to meet all objectives of the High Impact Specialized Innovation Program, as well as multiple CTSA program goals, with the following specific aims:
1) To generate a comprehensive transcriptional, immunologic, and proteomic profile of the normal porcine esophagus;
2) To develop and generate comprehensive transcriptional, immunologic, and proteomic profiles of porcine models of inflammatory/injury-induced and fibrotic esophageal diseases; and
3) To establish an integrated and self-sustaining center that shares resources with the scientific community to promote translational multidisciplinary research, fundamental hypothesis testing, and therapeutic drug and device development in esophageal diseases, as an initial platform for extension to other human diseases.
This highly innovative and impactful discovery-based and hypothesis-generating research will overcome roadblocks in translational science and enhance activities of the UNC/NC State CTSA UM1 HUB, successfully address a major impediment to translational science, and advance translation of drugs and devices to the clinic.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
North Carolina
United States
Geographic Scope
State-Wide
University Of North Carolina At Chapel Hill was awarded
Project Grant RC2TR005123
worth $768,064
from National Center for Advancing Translational Sciences in June 2025 with work to be completed primarily in North Carolina United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.350 National Center for Advancing Translational Sciences.
The Project Grant was awarded through grant opportunity Limited Competition: High Impact Specialized Innovation Programs in Clinical and Translational Science for UM1 CTSA Hub Awards (RC2 Clinical Trials Optional).
Status
(Ongoing)
Last Modified 7/21/25
Period of Performance
6/15/25
Start Date
5/31/30
End Date
Funding Split
$768.1K
Federal Obligation
$0.0
Non-Federal Obligation
$768.1K
Total Obligated
Activity Timeline
Transaction History
Modifications to RC2TR005123
Additional Detail
Award ID FAIN
RC2TR005123
SAI Number
RC2TR005123-3171279456
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NR00 NIH National Center for Advancing Translational Sciences
Funding Office
75NR00 NIH National Center for Advancing Translational Sciences
Awardee UEI
D3LHU66KBLD5
Awardee CAGE
4B856
Performance District
NC-90
Senators
Thom Tillis
Ted Budd
Ted Budd
Modified: 7/21/25