Dr. Bickenbach's research involves both understanding how aging affects epidermal stem cells and developing new molecular mechansims to reprogram skin keratinoccytes into pluripotent cells. Previously, they identified a subset of basal skin keratinocytes as stem cells. These cells have multipotent characteristics in that they can differentiate into various other types of cells and tissues, including neurons and B-lymphocytes. Her group is examining these cells to determine whether they have activated new signaling pathways during transdifferentiation. They have shown that the age of the keratinocyte stem cell has little effect on its multipotent capabilites, and thus could be used in translational or clinical cell-based therapies, especially to ameliorate age-related diseases. Currently, members of her group are using growth conditions, growth factors, and transient transfection to modulate the function of skin keratinocytes toward a pluripotent state. A primary objective is to understand how such conditions reprogram the keratinocytes into pluripotent cells, with an emphasis on epigenetic events and changes in levels of reactive oxygen species. The Bickenbach Lab's primary goals are to understand the mechansims that regulate reprogramming events, and to develop cell-replacement regimes that can be translated for human therapy. A third project involves the action of reactive oxygen species in modulating cell migration, with an emphasis on the effect of aging in such events.
Selected Publications:
Chinnathambi S, Bickenbach JR. Human skin and gingival keratinocytes show differential regulation of matrix metalloproteinases when combined with fibroblasts in 3-dimensional cultures. J Periodontol 76: 1072-1083, 2005. PMID: 16018749
Grinnell KL, Yang B, Eckert RL, Bickenbach JR. De-differentiation of mouse interfollicular keratinocytes by the embryonic transcription factor Oct-4. J Invest Dermatol (EPub Aug 24, 2006) 127: 372-380, 2007. PMID: 16932739
Stern MM, Bickenbach JR. Epidermal stem cells are resistant to cellular aging. Aging Cell (EPub Aug 6, 2007) 6: 439-452, 2007. PMID: 17635170
Grinnell KL, Bickenbach JR. Skin keratinocytes pretreated with embryonic stem cell conditioned medium or BMP4 can be directed to alternative cell lineages. Cell Proliferation (EPub doi:10.1111/j.1365-2148.2007.00464.x), 40: 685-705, 2007. PMID: 17877610
Stern MM, Tygrett LT, Waldschmidt TJ, Bickenbach JR. Cells isolated from the epidermis by Hoechst dye exclusion, small size, and negative selection for hematopoietic markers, can generate B lymphocyte precursors. J Invest Dermatol (EPub Dec 20, 2007), 128: 1386-1396, 2008. PMID: 18094731
Muffler S, Star H-J, Amoros M, Falkowska-Hansen B, Buehning T, Marme A, Bickenbach JR, Boukamp B. A stable niche supports long-term maintenance of human epidermal stem cells in organotypic cultures. Stem Cells (EPub July 24, 2008), 26: 2506-2515. 2008. PMID: 18653773
Racila D, Bickenbach JR. Are Epidermal stem cells unique with respect to aging? Aging (Open Access Impact Journals), online Aug 19, 2009.
