The long-range goal of this program project grant is to understand the basic molecular mechanisms involved in human cellular senescence and the reverse phenomenon of immortalization.
The specific aims are to: 1) Bring together five individual laboratories using disparate model systems of cellular senescence: normal human fibroblasts, adrenocortical cells and melanocytes and various immortal human cell lines; to work together on similar goals, using common techniques and approaches to answer questions regarding the molecular and cellular mechanisms involved in senescence and immortalization. These studies will examine the changes in gene expression that occur in cells as they are in vitro and in vivo, and will establish the differences and similarities in the pathways that lead to inhibition of cell proliferation. 2) Provide core facilities that are requisite for all the projects and thereby consolidate resources that will benefit the research at a much lower cost.
The aims of a program project will thereby be met, encouraging successful interactions and enhancing the utilization of common resources. 3) Provide a formal mechanism to promote research interactions via joint planning meetings.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG013663-04
Application #
2899779
Study Section
Special Emphasis Panel (ZAG1-DAG-1 (01))
Program Officer
Sierra, Felipe
Project Start
1996-04-11
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Young, Juan I; Sedivy, John M; Smith, James R (2003) Telomerase expression in normal human fibroblasts stabilizes DNA 5-methylcytosine transferase I. J Biol Chem 278:19904-8
Tominaga, Kaoru; Olgun, Abdullah; Smith, James R et al. (2002) Genetics of cellular senescence. Mech Ageing Dev 123:927-36
Thomas, Michael; Suwa, Tetsuya; Yang, Lianqing et al. (2002) Cooperation of hTERT, SV40 T antigen and oncogenic Ras in tumorigenesis: a cell transplantation model using bovine adrenocortical cells. Neoplasia 4:493-500
Zhang, Hao; Hornsby, Peter J (2002) Intradermal cell transplantation in soluble collagen. Cell Transplant 11:139-45
Hornsby, Peter J (2002) Aging of the human adrenal cortex. Ageing Res Rev 1:229-42
Tominaga, Kaoru; Pereira-Smith, Olivia M (2002) The genomic organization, promoter position and expression profile of the mouse MRG15 gene. Gene 294:215-24
Pardo, Patricia S; Leung, James K; Lucchesi, John C et al. (2002) MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation. J Biol Chem 277:50860-6
Hornsby, Peter J; Yang, Lianqing; Thomas, Michael (2002) Adrenocortical cell proliferation in a cell transplantation model: the role of SV40 T antigen. Endocr Res 28:777-83
Hornsby, Peter J (2002) Cellular senescence and tissue aging in vivo. J Gerontol A Biol Sci Med Sci 57:B251-6
Thomas, Michael; Wang, Xiangdong; Hornsby, Peter J (2002) Human adrenocortical cell xenotransplantation: model of cotransplantation of human adrenocortical cells and 3T3 cells in scid mice to form vascularized functional tissue and prevent adrenal insufficiency. Xenotransplantation 9:58-67

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