DF/HCC Program Affiliation

Head and Neck Cancer
Cutaneous Oncology and Melanoma

Research Abstract

The Rheinwald lab's research interest is growth regulation, replicative potential, stem character, and tumor suppressor mechanisms in epithelial cells and tissues. Most of our studies have been on the keratinocyte—the cell type that forms stratified squamous epithelia such as the oral, corneal, conjunctival, and exocervical epithelia, and the epidermis, and the mesothelial cell--the cell type that forms the simple lining epithelium that covers the inner surfaces of the body cavities (peritoneal, pleural, and pericardial) and the outer surfaces of all the organs conteined within these cavities. As "comparative cell biologists", we also study other epithelial cell types, including myoepithelial, urothelial, and prostate, tracheobronchial, endocervical, and mammary epithelial cells. Our experimental system is primary cell lines cultured from human tissue specimens. We use retroviral and lentiviral vectors to stably express or knock down the expression of specific oncogenes and other growth regulatory genes in these cells, seeking to understand the molecular basis of complex biological systems and pathologies. Other experimental tools we use include immunohistochemistry, Western blotting, flow cytometry, DNA microarray analysis of gene expression, and PCR. Our current research projects are (1) elucidating the signal pathways responsible for a coupled Laminin 5- and p16INK4A-dependent hypermotility and growth arrest mechanism actived during wound healing and as a tumor suppressor in many epithelia, (2) oxidative stress-related replicative lifespan attenuation in mesothelial cells, and (3) characterizing somatic epithelial cell types derived from human embryonic stem cells in culture.

Publications

• Natarajan E, Omobono JD, Guo Z, Hopkinson S, Lazar AJ, Brenn T, Jones JC, Rheinwald JG.A keratinocyte hypermotility/growth-arrest response involving laminin 5 and p16INK4A activated in wound healing and senescence.Am J Pathol 2006 Jun;168(6):1821-37.
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• Iuchi S, Dabelsteen S, Easley K, Rheinwald JG, Green H.Immortalized keratinocyte lines derived from human embryonic stem cells.Proc Natl Acad Sci U S A 2006 Feb 7;103(6):1792-7.
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• Gordon GJ, Rockwell GN, Jensen RV, Rheinwald JG, Glickman JN, Aronson JP, Pottorf BJ, Nitz MD, Richards WG, Sugarbaker DJ, Bueno R.Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transc
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• Natarajan E, Saeb M, Crum CP, Woo SB, McKee PH, Rheinwald JG.Co-expression of p16(INK4A) and laminin 5 gamma2 by microinvasive and superficial squamous cell carcinomas in vivo and by migrating wound and senescent keratinocytes in culture.Am J Pathol 2003
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• Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA, Louis DN, Li FP, Rheinwald JG.Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiat
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• Schön M, Benwood J, O'Connell-Willstaedt T, Rheinwald JG.Human sweat gland myoepithelial cells express a unique set of cytokeratins and reveal the potential for alternative epithelial and mesenchymal differentiation states in culture.J Cell Sci 1999 Jun;1
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