Technologies originally developed in one field of research (e.g. cancer), is sometimes slow to be introduced in other fields (e.g. wound healing). The overall objective of this application is to apply one such advance, in vivo combinatorial biology, to wound healing (WH) so as to create and modify potential WH biotherapeutics. We will screen for new therapeutics with 4 technologies: (1) Biopanning to identify targeting peptides for the ischemic wound for better drug delivery; (2) SNAAP screening to create pharmacologically optimized growth factor chimera with improved pharmacokinetics for wound repair; (3) LIVE recoveries to evolve a gene delivery vector, genetically optimized for the WH milieu and (4) RBT to identify cell surface biomarking signatures on bone marrow-derived precursor cells that can migrate to and engraft the wound. Innovation: Combinatorial technologies have never been applied to a wound healing paradigm. Because phage display can answer research questions like no other technique; it will open new venues of WH research. It will increase basic understanding of WH mechanisms, identify intrinsically useful biomarking signatures and create new biotherapeutic agents. Need for a multidisciplinary team: Phage display fails as a """"""""molecular biology kit"""""""" and multidisciplinary skills in cores and projects provide (1) specific experience to create, optimize and analyze libraries (QA/QC, inventory), (2) access to prototypic wound healing models, (3) the ability to design, develop and test ideal prototypic screens and (4) the hit to lead transformation for the wound healing community. Impact on wound healing: Combinatorial techniques could be applied to virtually any WH paradigm (e.g. trauma burns). It will generate unique research reagents, preclinical candidates, pharmacologically improved gene vectors and a better understanding of progenitor, stem and stromal cell targeting to WH. It can have ancillary applications in all kinds of different WH paradigms. Relevance to public health: Progress in ambulatory care increases pressures to accelerate normal WH, minimize reconstructive surgery, modify scar formation and return the patient to the workplace. Technologies originally developed for other disciplines, generates completely new ways to enhance, modify and understand the WH response in a fashion that can impact all kinds of different kinds of wounds. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
7P20GM078421-03
Application #
7573778
Study Section
Special Emphasis Panel (ZGM1-PPBC-9 (WH))
Program Officer
Ikeda, Richard A
Project Start
2006-08-01
Project End
2010-07-31
Budget Start
2007-09-01
Budget End
2008-07-31
Support Year
3
Fiscal Year
2007
Total Cost
$481,972
Indirect Cost
Name
University of California San Diego
Department
Surgery
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Costantini, Todd W; Meads, Morgan; Dang, Xitong et al. (2016) The Response to Burn Injury in Mice With Human Hematolymphoid Systems. Ann Surg 263:199-204
Podvin, Sonia; Miller, Miles C; Rossi, Ryan et al. (2016) The Orphan C2orf40 Gene is a Neuroimmune Factor in Alzheimer's Disease. JSM Alzheimers Dis Relat Dement 3:
Costantini, Todd W; Dang, Xitong; Coimbra, Raul et al. (2015) CHRFAM7A, a human-specific and partially duplicated ?7-nicotinic acetylcholine receptor gene with the potential to specify a human-specific inflammatory response to injury. J Leukoc Biol 97:247-57
Costantini, Todd W; Coimbra, Raul; Lopez, Nicole E et al. (2015) Monitoring Neutrophil-Expressed Cell Surface Esophageal Cancer Related Gene-4 after Severe Burn Injury. Surg Infect (Larchmt) 16:669-74
Kao, Steven; Shaterian, Ashkaun; Cauvi, David M et al. (2015) Pulmonary preconditioning, injury, and inflammation modulate expression of the candidate tumor suppressor gene ECRG4 in lung. Exp Lung Res 41:162-72
Lee, Jisook; Dang, Xitong; Borboa, Alexandra et al. (2015) Thrombin-processed Ecrg4 recruits myeloid cells and induces antitumorigenic inflammation. Neuro Oncol 17:685-96
Podvin, Sonia; Dang, Xitong; Meads, Morgan et al. (2015) Esophageal cancer-related gene-4 (ECRG4) interactions with the innate immunity receptor complex. Inflamm Res 64:107-18
Torbett, Bruce E; Baird, Andrew; Eliceiri, Brian P (2015) Understanding the rules of the road: proteomic approaches to interrogate the blood brain barrier. Front Neurosci 9:70
Dang, Xitong; Eliceiri, Brian P; Baird, Andrew et al. (2015) CHRFAM7A: a human-specific ?7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS. FASEB J 29:2292-302
Baird, Andrew; Lee, Jisook; Podvin, Sonia et al. (2014) Esophageal cancer-related gene 4 at the interface of injury, inflammation, infection, and malignancy. Gastrointest Cancer 2014:131-142

Showing the most recent 10 out of 58 publications