The long term objective of the proposed research is to learn what controls whether injuries heal with scarring/fibrosis versus full regeneration of los structures. The human health burden of fibrosis and scarring is enormous and affects every tissue from heart (lost heart function after a myocardial infarction) to lung (idiopathic lung fibrosis). Enhancing regeneration could prevent for example the almost universal recurrence of chronic wounds in the exact location where they previously appeared. We use the Wound Induced Hair Neogenesis (WIHN) model system where in the center of excisional wounds in mice a variable amount of regeneration occurs and de novo hair follicles form in a recapitulation of embryogenesis. The goal of this grant is to understand the factors which control the frequency of regeneration. We will directly test the mechanism and the ability for candidate molecules which enhance regeneration in mice to do so in human subjects. The results of this grant promise to help define new treatments and diagnostics to enhance regeneration and wound healing.

Public Health Relevance

Our body's response to a wound is often inadequate; instead of full regeneration of our injured tissue, we heal with scars and fibrosis. These scars do not function as the previous tissue did, which explains why for example most chronic wounds recur in the exact spot they first appeared. The relevance of the present studies of both mouse and human wounds is to try to understand the factors which control regeneration versus scarring; we will also directly test compounds in human subjects to try to demonstrate regeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR068280-02
Application #
9338120
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Tseng, Hung H
Project Start
2016-09-01
Project End
2019-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Dermatology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Aguh, Crystal; Dina, Yemisi; Talbot Jr, C Conover et al. (2018) Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol 79:904-912.e1
Islam, Nasif; Garza, Luis A (2018) Adipose and Hair Function: An aPPARent Connection. J Invest Dermatol 138:480-482
Zhu, Amadeus S; Li, Ang; Ratliff, Tabetha S et al. (2017) After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration. J Invest Dermatol 137:1562-1568
Vandiver, Amy; Girardi, Nicholas; Alhariri, Jihad et al. (2017) Two cases of alopecia areata treated with ruxolitinib: a discussion of ideal dosing and laboratory monitoring. Int J Dermatol 56:833-835
Kim, Dongwon; Garza, Luis A (2017) The Negative Regulator CXXC5: Making WNT Look a Little Less Dishevelled. J Invest Dermatol 137:2248-2250
Yang, Steven Hoseong; Qi, Ji; Esandrio, Jessica et al. (2015) Efficacy and Tolerability of a Novel Biopsy Device for Removing Benign Epidermal Skin Lesions. Dermatol Surg 41:1264-73