James George Rheinwald, Ph.D.
|Title||Associate Professor of Dermatology|
|Institution||Brigham and Women's Hospital|
|Address||Brigham and Women's Hospital|
77 Avenue Louis Pasteur
Boston MA 02115
The research interest of the Rheinwald laboratory is to understand the mechanisms that regulate growth, differentiation, motility, and malignant transformation of epithelial cells. Our major focus is the keratinocyte—the cell type that forms stratified squamous epithelial tissues, which include the epidermis and the oral, corneal, conjunctival, esophageal, and exocervical epithelia. We also study prostate epithelial cells, pleural and peritoneal mesothelial cells, sweat gland myoepithelial cells, and somatic epithelial cells derived from embryonic stem cells. We use human cell culture model systems and a genetic engineering approach: using retroviral and lentiviral expression and shRNA vectors to investigate the roles of specific proteins in key cellular mechanisms. Our lab is currently devoting its effort to two projects.
The first seeks to understand the mechanisms and associated markers of neoplastic progression in the epidermis and oral epithelium toward squamous cell carcinoma (SCC). We have identified p16INK4A and Laminin ?2 chain overexpression in late stage premalignant dysplastic lesions of these epithelia in vivo and are investigating SCC cells and engineered keratinocyte models to find cause and effect relationships between hyperstimulation of mitogen and survival signal pathways and Laminin ?2 dysregulation. These studies seek to identify prognostic immunohistochemical markers and potential targets for kinase inhibitors to identify and treat premalignant lesions at an early stage, before they become large, deeply invasive, and incurable cancers.
The second project seeks to understand the role of the transcriptional regulator p63 in determining expression of a set of cell-substratum adhesion proteins and growth control mechanisms that are shared by a large family of epithelial cell types and play important roles in the maintenance of tissue stem cell character. We are engineering cells to stably express or to knock down expression of p63 to determine the consequences to cell type identity, patterns of gene and protein expression, and growth control mechanisms.
Dr. Rheinwald also directs a Cell Culture Core. The Core provides well-characterized primary human cell lines, squamous cell carcinoma-derived, TERT-immortalized, and other engineered cell lines from our large cryopreserved collection. The Core also provides other services, as described on the Rheinwald lab website: http://rheinwaldlab.bwh.harvard.edu.
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