Somatic stem cells reside in many tissues, including skin and oral epithelia, and are responsible for tissue maintenance and repair. The goal of regenerative medicine is to use these cells for gene and cell replacement therapies for genetic and acquired diseases. However, long-term stem cell-based therapy requires overcoming potential host responses as well as new insights into basic stem cell biology. Accordingly, Dr. Ghazizadeh's lab is currently focusing on two projects addressing the critical issues in epithelial stem cell-based therapies: 1) Transplantation of stem cells expressing a neoantigen or alloantigen induces immune responses thereby limiting the therapy. Accordingly, she has developed animal models to follow the fate of transplanted stem cells in live mice and characterize the potential host responses. Currently, she is focusing on developing strategies to overcome host immune responses in stem cell-based gene and cell therapy; 2) Instructive signals from the microenvironment may impose stem cell features on other cells, suggesting that non-stem cells can be used as a source of progenitors for cell and gene therapy. De-differentiation, the progression of cells from a more to a less differentiated state, is observed in a variety of processes such as cancer and tissue regeneration. However, the cellular and molecular mechanisms that control de-differentiation are little understood. Her lab has recently developed a model in which epithelial cells that are, by all measures, terminally differentiated are able to reform a fully functional tissue when implanted into a full thickness wound bed in mice, suggesting that terminally differentiated cells were de-differentiated to stem cells. She is currently exploring factors in the microenvironment that are responsible for this reprogramming. Such studies are likely to offer new insights into fundamental mechanisms of de-differentiation and reprogramming, impacting all aspects of epidermal and stem cell biology, including wound healing, tissue regeneration, and aging.
Mannik J, Alzayady K, Ghazizadeh S. Regeneration of multilineage skin epithelia by differentiated keratinocytes. J Invest Dermatol. 2010 Feb;130(2):388-97.
Zhang Z, Kuscu C, Ghazizadeh S. Transgene-specific host responses in cutaneous gene therapy: the role of cells expressing the transgene. Gene Ther. 2009 Sep;16(9):1138-45.
Lu Z, Ghazizadeh S. Loss of transgene following ex vivo gene transfer is associated with a dominant Th2 response: implications for cutaneous gene therapy. Mol Ther. 2007 May;15(5):954-61. Epub 2007 Mar 13.
Ghazizadeh, S., Taichman, L.B., (2005) Organization of stem cells and their progeny in human epidermis. Invest. Dermatol. (124:367-372.
Ghazizadeh S, Katz AB, Harrington R, Taichman LB. Lentivirus-mediated gene transfer to human epidermis. J Investig Dermatol Symp Proc. 2004 Sep;9(3):269-75.
Ghazizadeh S, Taichman LB. Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. EMBO J. 2001 Mar 15;20(6):1215-22.