This laboratory is devoted to the study of the human keratinocyte; its multiplication, its terminal differentiation, and its specific gene expression. The keratinocyte is a unique example of a terminally differentiating cell type with high susceptibility to neoplastic change. Because the cell type is now so efficiently cultivable and exhibits many differentiated properties in culture, most of the work uses cell cultures. However, the cultures are readily transplantable to athymic animals where they generate normal human epidermis. This is a very sensitive test for normal keratinocytes; transformation of the cultured cells with a viral oncogene results in very evident perturbation of the differentiated structure of the grafted epithelium. There is no other tissue which can be easily generated from cultured cells and studied this way. Much of the work will be focused on regulated gene expression, using involucrin and other specialized proteins of terminal differentiation. In this work, study of transfected genes and their resulting expression in small (proliferating) and large (terminally differentiating) cells, separated by elutriation, has already shown that genes are expressed with tissue and cell compartment specificity. Changes in gene expression after grafting of cultured cells will be studied. The signals that turn on gene expression in large cells must be closely related to those that arrest proliferation, since altered gene expression is basic to the development of neoplasia.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA040029-10
Application #
2090068
Study Section
Special Emphasis Panel (SRC (88))
Project Start
1985-07-01
Project End
1999-04-30
Budget Start
1994-06-21
Budget End
1995-04-30
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Harvard University
Department
Physiology
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Simon, M; Phillips, M; Green, H et al. (1989) Absence of a single repeat from the coding region of the human involucrin gene leading to RFLP. Am J Hum Genet 45:910-6
Morgan, J R; Barrandon, Y; Green, H et al. (1987) Expression of an exogenous growth hormone gene by transplantable human epidermal cells. Science 237:1476-9
Lewis, L; Barrandon, Y; Green, H et al. (1987) The reorganization of microtubules and microfilaments in differentiating keratinocytes. Differentiation 36:228-33