Dermatology; Epidermis; Homeostasis; Pathology; Regeneration; Stem Cells; Wound Healing; Carcinogenesis
Understanding how stem cells are regulated to promote tissue regeneration is key to developing targeted therapies to treat human diseases that lead to either tissue damage or uncontrolled growth in cancer. My research uses innovative technology to examine how a key stem cell molecular signals can recruit cells to undergo collective growth during normal tissue regeneration and how this mechanism can also be utilized aberrantly to promote cooperative growth during carcinogenesis.
Specialized Terms: Hair follicle stem cells; skin regeneration; wound healing
Extensive Research Description
Tissue homeostasis and regeneration are mediated by the coordinated growth of multiple cell types to generate tissue that sustains integrity and function of the organism. This ability to durably regenerate tissue relies on adult stem cells that reside in a specialized environment called the niche, which influences their self-renewal, growth and differentiation. Failure to maintain or mobilize stem cells results in tissue loss and dysfunction, while uncontrolled activation of these cells can fuel disorganized growth and cancer. Elucidating how key molecular signals govern stem cell behavior holds tremendous implications for designing targeted therapies to treat human diseases. A major challenge to examining how mammalian stem cells are regulated is the inability of conventional static analysis to follow the fate and behavior of cell populations in vivo over time.
My research aims to address a major gap in our knowledge of how signals can engage a population of undifferentiated cells to yield robust and organized growth. In particular, is still unclear (1) what cellular behaviors such as cell divisions and movement are regulated by key morphogenetic signals during regeneration, (2) how these signals are disseminated throughout a field of cells in to ensure robust but compartmentalized growth, and (3) how these mechanisms can contribute to disorganized and uncontrolled growth during tumorigenesis. The hair follicle is the ideal model to address these questions as it is exceptionally accessible and undergoes well-characterized cyclical regeneration in a manner dependent on resident stem cells. By coupling this model to a novel live imaging technique we are now uniquely poised to address these outstanding questions.
Specifically, I have examined how Wnt/β-catenin signaling, a key molecular pathway required for hair follicle regeneration, is propagated throughout a population of undifferentiated cells to promote synchronous and coordinated growth. By live imaging, we have found that only a subset of cells is required to fuel the non-cell autonomous activation of this signal and growth behaviors throughout surrounding epithelial cells and is associated with upregulation of diffusible Wnt ligands. One of my goals is to understand how cooperative epithelial growth coordinates normal hair follicle regeneration. The second is to examine how this mechanism of collective behavior regulates basal cell carcinomas (BCCs), the most common human skin cancer, which utilizes hair morphogenetic signals for growth. Third, I am interested in understanding how the mesenchyme regulates both organized regeneration and development and how we can apply this knowledge to modify tumor growth. Accomplishing these aims will provide novel insight into the principle mechanisms that ensure proper tissue regeneration and how they can also be exploited deleteriously to promote collective growth in cancer.
- Deschene E*, Myung P*, Rompolas P, Zito G, Taketo M, Saotome I, and V. Greco. 2014. ß-catenin activation regulates tissue growth via a non-cell autonomous mechanism within the hair stem cell niche. Science. 343:1353-1356. * Co-first author
Epithelial Wnt ligand secretion is required for adult hair follicle regeneration.
Myung, P., Takeo, M., Ito M., and R. Atit. 2013. Epithelial Wnt ligand secretion is required for adult hair follicle regeneration. J. Invest. Dermatol. 133:31-41.
Dissecting the bulge in hair regeneration.
Myung, P. and M. Ito. 2012. Dissecting the bulge in hair regeneration. J. Clin. Invest. 122:448-454.
Coordinated activation of Wnt signaling in epithelial and melanocyte stem cells in a shared niche initiates pigmented hair follicle regeneration.
Rabbani, P., Takeo, M., Chou, W., Myung, P., Bosenberg, M., Chin, L., and M. Ito. 2011. Coordinated activation of Wnt signaling in epithelial and melanocyte stem cells in a shared niche initiates pigmented hair follicle regeneration. Cell. 145:941-955..
- Hardwiring stem cell communication through tissue structure. Xin T, Greco V, & Myung P. (2016). Hardwiring stem cell communication through tissue structure. Cell. 164:1212-1225. PMCID: PMC4805424
Full List of PubMed Publications
- Sun Q, Rabbani P, Takeo M, Lee SH, Lim CH, Noel ES, Taketo MM, Myung P, Millar S, Ito M: Dissecting Wnt signaling for melanocyte regulation during wound healing. J Invest Dermatol. 2018 Feb 8; 2018 Feb 8. PMID: 29428355
- Xin T, Greco V, Myung P: Hardwiring Stem Cell Communication through Tissue Structure. Cell. 2016 Mar 10. PMID: 26967287
- Neckman JP, Kim J, Mathur M, Myung P, Girardi M: Diverse cutaneous manifestations of Erdheim-Chester disease in a woman with a history of Langerhans cell histiocytosis. JAAD Case Rep. 2016 Mar; 2016 Mar 5. PMID: 27051852
- Myung P, Greco V: Stem Cells Show Parental Control. Cell. 2015 Jul 30. PMID: 26232219
- Mesa KR, Rompolas P, Zito G, Myung P, Sun TY, Brown S, Gonzalez DG, Blagoev KB, Haberman AM, Greco V: Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool. Nature. 2015 Jun 4; 2015 Apr 6. PMID: 25849774
- Deschene ER, Myung P, Rompolas P, Zito G, Sun TY, Taketo MM, Saotome I, Greco V: β-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche. Science. 2014 Mar 21. PMID: 24653033
- Myung PS, Takeo M, Ito M, Atit RP: Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration. J Invest Dermatol. 2013 Jan; 2012 Jul 19. PMID: 22810306
- Myung P, Ito M: Dissecting the bulge in hair regeneration. J Clin Invest. 2012 Feb; 2012 Feb 1. PMID: 22293183
- Rabbani P, Takeo M, Chou W, Myung P, Bosenberg M, Chin L, Taketo MM, Ito M: Coordinated activation of Wnt in epithelial and melanocyte stem cells initiates pigmented hair regeneration. Cell. 2011 Jun 10. PMID: 21663796
- Myung P, Andl T, Ito M: Defining the hair follicle stem cell (Part II). J Cutan Pathol. 2009 Oct. PMID: 19712246
- Myung P, Andl T, Ito M: Defining the hair follicle stem cell (Part I). J Cutan Pathol. 2009 Sep. PMID: 19674210
- Myung PS, Kundu M, Abboud SK: Eosinophilic granuloma manifesting as painless cervical lymphadenopathy in a patient positive for human immunodeficiency virus 1. Arch Otolaryngol Head Neck Surg. 2008 Feb. PMID: 18283165
- Singer AL, Bunnell SC, Obstfeld AE, Jordan MS, Wu JN, Myung PS, Samelson LE, Koretzky GA: Roles of the proline-rich domain in SLP-76 subcellular localization and T cell function. J Biol Chem. 2004 Apr 9; 2004 Jan 13. PMID: 14722089
- Nichols KE, Haines K, Myung PS, Newbrough S, Myers E, Jumaa H, Shedlock DJ, Shen H, Koretzky GA: Macrophage activation and Fcgamma receptor-mediated signaling do not require expression of the SLP-76 and SLP-65 adaptors. J Leukoc Biol. 2004 Mar; 2003 Dec 23. PMID: 14694181
- Judd BA, Myung PS, Obergfell A, Myers EE, Cheng AM, Watson SP, Pear WS, Allman D, Shattil SJ, Koretzky GA: Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling. J Exp Med. 2002 Mar 18. PMID: 11901197