The long term objective of the proposed research is to learn how to effectively use cellular therapy in regenerative medicine, especially as pertains to dermatology. In particular, our goal is to convert the identity of skin at the stump site of amputees to thick palmo/plantar (volar) type skin to enhance their use of prosthetics. Towards this clinical goal we first will define the basic genetic control of volar fibroblast skin identity Then we will define homeostatic mechanisms whereby non-volar tissue retains its identity. In so doing, we will optimize conditions for our final effort to use autologous fibroblasts to induce ectopic volar skin in volunteers. We will fully excise this ectopic acral skin as a proof-of-concep trial and a prelude to clinical optimization and use in amputees.

Public Health Relevance

Cellular therapy holds great promise in regenerative medicine. The long term goal of this grant is to help amputees who cannot frequently wear their prosthetics because of pain and skin break-down. In order to enhance their use of prosthetics, we will attempt to convert the identity of skin located at the stump to the same type as normally found at the palms and soles-thick skin which is naturally friction and irritant resistant.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR064297-02
Application #
8713420
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Tseng, Hung H
Project Start
2013-09-01
Project End
2018-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$344,250
Indirect Cost
$131,750
Name
Johns Hopkins University
Department
Dermatology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Nelson, Amanda M; Katseff, Adiya S; Ratliff, Tabetha S et al. (2016) Interleukin 6 and STAT3 regulate p63 isoform expression in keratinocytes during regeneration. Exp Dermatol 25:155-7
Nelson, Amanda M; Katseff, Adiya S; Resnik, Sydney R et al. (2016) Interleukin-6 Null Mice Paradoxically Display Increased STAT3 Activity and Wound-Induced Hair Neogenesis. J Invest Dermatol 136:1051-3
Kim, Dongwon; Hossain, M Zulfiquer; Nieves, Ashley et al. (2016) To Control Site-Specific Skin Gene Expression, Autocrine Mimics Paracrine Canonical Wnt Signaling and Is Activated Ectopically in Skin Disease. Am J Pathol 186:1140-50
Vandiver, Amy R; Irizarry, Rafael A; Hansen, Kasper D et al. (2015) Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin. Genome Biol 16:80
Nelson, Amanda M; Reddy, Sashank K; Ratliff, Tabetha S et al. (2015) dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration. Cell Stem Cell 17:139-51
Kim, Dongwon; Garza, Luis A (2015) A new target for squamous cell skin cancer? Exp Dermatol 24:14-5
Hossain, M Zulfiquer; Garza, Luis A (2015) Hairy math: addition of Wnt-3a to multiply bulge cells. J Invest Dermatol 135:1481-3
Nelson, Amanda M; Garza, Luis A (2015) Bad Hair Day: Testosterone and Wnts. J Invest Dermatol 135:2567-9
Nieves, Ashley; Garza, Luis A (2014) Does prostaglandin D2 hold the cure to male pattern baldness? Exp Dermatol 23:224-7
Qi, Ji; Garza, Luis A (2014) An overview of alopecias. Cold Spring Harb Perspect Med 4:

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