One of the great mysteries in biology is how do certain animals regenerate lost body parts in response to trauma. Few examples of tissue regeneration exist in mammals, and studies of tissue regeneration in non- mammalian species are limited by a lack of molecular tools. This research plan aims to elucidate how mammalian tissue regeneration unfolds in a genetically defined mouse model of tissue regeneration.
Aim #1 will determine the cellular basis of tissue regeneration utilizing developmental biology, lineage tracing, and conditional mouse genetics.
Aim #2 will determine the role of a specific protein in regulating gene expression and chromatin accessibility during tissue regeneration.
Aim #2 will utilize quantitative mRNA sequencing (RNA-Seq) and a new technique to footprint chromatin accessibility (ATAC-Seq). Successful completion of the proposed aims will greatly advance our understanding of how mammalian tissue regeneration unfolds, and this knowledge may offer insights on how to trigger tissue regeneration in humans and impact future strategies in regenerative medicine. This award will enable the principle investigator, a dermatology trained physician-scientist, to receive intensive training in skin biology, developmental biology, and genomics, and to develop an independent research program. Additionally, Dr. Leung will complete structured career development including didactic sessions, training in ethical conduct, and training in laboratory management. Stanford University is providing him full institutional support, extensive resources, and opportunity for collaborations with experts in the field. The Stanford Department of Dermatology has a strong track record in mentoring dermatology physician-scientists to independent positions. This award will help Dr. Leung transition to a full-time academic tenure-track position where he will spend 90% of his time on research and 10% on clinical activities.

Public Health Relevance

This proposal is focused on understanding on a cellular and molecular level how tissue regeneration works in mice. Studying how this process functions in other mammals may offer insights on how to trigger tissue regeneration in humans and impact future strategies in regenerative medicine.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Clinical Investigator Award (CIA) (K08)
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Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
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Baker, Carl
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Stanford University
Schools of Medicine
United States
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Nishiguchi, Mailyn A; Spencer, Casey A; Leung, Denis H et al. (2018) Aging Suppresses Skin-Derived Circulating SDF1 to Promote Full-Thickness Tissue Regeneration. Cell Rep 24:3383-3392.e5
Gorell, Emily S; Leung, Thomas H; Khuu, Phuong et al. (2015) Purified type I collagen wound matrix improves chronic wound healing in patients with recessive dystrophic epidermolysis bullosa. Pediatr Dermatol 32:220-5
Leung, Thomas H; Snyder, Emily R; Liu, Yinghua et al. (2015) A cellular, molecular, and pharmacological basis for appendage regeneration in mice. Genes Dev 29:2097-107
Danial, Christina; Tichy, Andrea L; Tariq, Umar et al. (2014) An open-label study to evaluate sildenafil for the treatment of lymphatic malformations. J Am Acad Dermatol 70:1050-7
Sebastiano, Vittorio; Zhen, Hanson Hui; Haddad, Bahareh et al. (2014) Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci Transl Med 6:264ra163