The long-term goal of this project is to develop better treatments for wounds, alopecias and other degenerative skin disorders by elucidating the cellular and molecular mechanisms of skin regeneration following wounding. We demonstrated that adult mice have the capacity to regenerate hair follicles, sebaceous glands and fat following a full thickness wound. We have evidence that Wnt, Fgf, Hh pathways and gamma/delta T cells are vital players controlling this wound induced hair follicle neogenesis (WIHN). We hypothesize that manipulation of these molecular pathways at the right time and place will convert non-regenerative tissue into regenerative tissue with the ability to form hair follicles, sebaceous glands and fat in response to wounding. To test this hypothesis, we will determine: 1. The role of dermal Wnt/ss-catenin signaling in hair follicle neogenesis using transgenic and conditional knockout mice, 2. The cellular origin of nascent hair follicles in the wound using promoters targeting fibroblasts, myofibroblasts, hair follicle dermal papilla and other dermal subpopulations for lineage analysis, 3. The role of sonic hedgehog signaling in the ability to coax healing wounds to regenerate rather than scar. Human skin xenografted to immunodeficient mice will be studied for its ability to respond with follicular neogenesis to Wnt and/or Shh activation. Ultimately, our findings will yield insights into scarless wound healing tht have implications for understanding skin biology and developing future treatments for wounds, alopecia and other degenerative skin disorders.

Public Health Relevance

Scars typically lack hair follicles. We are developing ways to regenerate hair follicles after wounding by taking advantage of genetically manipulated mice that heal with little scarring. These studies will ultimately benefit people with wounds, scars, alopecias and other degenerative skin disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR055309-06A1
Application #
8505685
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Baker, Carl
Project Start
2007-07-12
Project End
2018-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
6
Fiscal Year
2013
Total Cost
$340,000
Indirect Cost
$127,500
Name
University of Pennsylvania
Department
Dermatology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Thangapazham, Rajesh L; Klover, Peter; Wang, Ji-an et al. (2014) Dissociated human dermal papilla cells induce hair follicle neogenesis in grafted dermal-epidermal composites. J Invest Dermatol 134:538-40
Garza, Luis A; Liu, Yaping; Yang, Zaixin et al. (2012) Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. Sci Transl Med 4:126ra34
Yang, Chao-Chun; Cotsarelis, George (2010) Review of hair follicle dermal cells. J Dermatol Sci 57:2-11