Ruby Shalom-Feuerstein, PhD
Assistant Professor of Medicine
PhD - Tel Aviv University, 2007
Epithelial stem cells and pathophysiology
Our body is covered by tightly packed stratified epithelial tissues that protect us against external insults, such as infections, toxicants, and irradiation. The skin and the corneal epithelia share many common features in terms of structure, function, stem cell regeneration and pathologies. We explore the molecular events that underlie the morphogenesis, stem cell homeostasis, and pathophysiology of the skin and the cornea. Our objective is to improve understanding of embryonic epithelial lineage specification and adult tissue regeneration, with the goal of translating this knowledge into new treatments.
We employ complementary approaches, some of which were uniquely developed in our lab, to identify protein coding genes and microRNAs that regulate these biological processes. Technologies we employ include: induced pluripotent stem cell and adult keratinocyte stem cell culture, organotypic cultures, genetic mouse models, lineage tracing and molecular biology.
Golan T, Messer AR, Amitai-Lange A, Melamed Z, Ohana R, Bell RE, Kapitansky O, Lerman G, Greenberger S, Khaled M, Amar N, Albrengues J, Gaggioli C, Gonen P, Tabach Y, Sprinzak D, Shalom-Feuerstein R, and Levy C. 2015. Interactions of melanoma cells with distal keratinocytes trigger metastasis via notch signaling inhibition of MITF. Mol Cell.
Amitai-Lange A, Altshuler A, Bubley J, Dbayat N, Tiosano B, and Shalom-Feuerstein R. 2015. Lineage tracing of stem and progenitor cells of the murine corneal epithelium. Stem Cells. 33, 230-9.
Shalom-Feuerstein R, Serror L, Aberdam E, Müller FJ, Van Bokhoven H, Wiman KG, Zhou H, Aberdam R, and Petit P. 2013. Impaired epithelial differentiation of induced pluripotent stem cells from EEC patients is rescued by APR-246/PRIMA-1MET. Proc Natl Acad Sci USA 110, 2152-6.
Shalom-Feuerstein R, Serror L, de la Forest Divonne S, Petit I, Aberdam E, Camargo L, Damour O, Vigouroux C, Solomon A, Gaggioli C, Itskovitz-Eldor J, Ahmad S, and Aberdam D. 2012. Pluripotent stem cell model reveals essential roles for miR-450b-5p and miR-184 in embryonic corneal lineage specification. Stem Cells 30, 898-909.
This paper was chosen for the cover of the month's Stem Cells issue.
Shalom-Feuerstein R, Lena AM, Zhou H, De La Forest Divonne S, Van Bokhoven H, Candi E, Melino G, and Aberdam D. 2011. ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis. Cell Death Differ. 18, 887-96.
Tracking the origin and fate of stem cells in the mouse cornea under homeostasis and injury (Amitai-Lange, Stem Cells 2015).
Accumulating evidence supports the dogma that the corneal epithelium is regenerated by stem cells located exclusively in the limbal niche, at the corneal periphery. However, this topic has remained highly debated in recent years. Here, lineage tracing experiments using R26R-Confetti mice were performed to track limbal and corneal epithelial stem/progenitor cells randomly induced to express four fluorescent genes (A). Four months following induction of cell tagging (B), radial limbal stripes of migrating stem cell progeny extended between the limbus and the corneal center, much slower than expected, reaching the corneal center within 4-5 months. Strikingly, large limbal streaks appeared within a week under wounding conditions (C). These data suggest that the mouse limbus serves as the stem cell niche and largely contributes to corneal homeostasis and repair. Further, the data indicate that corneal progenitor cells have a longer turnover than previously considered and, therefore, may maintain the corneal epithelium over a period of several months.