Abstract

This multidisciplinary program focuses on the molecular mechanisms involved in cell survival and on the modalities whereby conventional anti- cancer agents interfere with the function of anti-apoptosis proteins. The program has four projects. There is also request for an administrative and a nucleic acids core component. The investigators intend to study the mechanisms involved in protection from apoptosis by the oncoprotein BCR/ABL and the role of BCR/ABL- dependent anti-apoptotic pathways in leukemogenesis pathways in leukemogenesis, the functional relationship between IGF-1 receptor and BCL-2 family members and the role of this pathway in apoptosis protection, the relevance of post-translational modification of BCL-2 in the anti-tumor effects of certain conventional anti-cancer agents, and the regulation of apoptosis and survival via signals involving novel members of the tumor necrosis factor receptors. The four principal investigators are established and very productive researchers with outstanding track records in the study of cell proliferation, survival, and neoplastic transformation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA078890-02
Application #
6173981
Study Section
Subcommittee G - Education (NCI)
Program Officer
Spalholz, Barbara A
Project Start
1999-06-01
Project End
2002-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
2
Fiscal Year
2000
Total Cost
$1,064,985
Indirect Cost

  Institution

Name
Thomas Jefferson University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107

  Publications

Zou, Yaqun; Zwolanek, Daniela; Izu, Yayoi et al. (2014) Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice. Hum Mol Genet 23:2339-52
Lidonnici, Maria Rosa; Audia, Alessandra; Soliera, Angela Rachele et al. (2010) Expression of the transcriptional repressor Gfi-1 is regulated by C/EBP{alpha} and is involved in its proliferation and colony formation-inhibitory effects in p210BCR/ABL-expressing cells. Cancer Res 70:7949-59
Bellodi, Cristian; Lidonnici, Maria Rosa; Hamilton, Ashley et al. (2009) Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J Clin Invest 119:1109-23
Chen, Jia; Capozza, Franco; Wu, An et al. (2008) Regulation of insulin receptor substrate-1 expression levels by caveolin-1. J Cell Physiol 217:281-9
Fernandes-Alnemri, Teresa; Alnemri, Emad S (2008) Assembly, purification, and assay of the activity of the ASC pyroptosome. Methods Enzymol 442:251-70
Trapasso, Francesco; Pichiorri, Flavia; Gaspari, Marco et al. (2008) Fhit interaction with ferredoxin reductase triggers generation of reactive oxygen species and apoptosis of cancer cells. J Biol Chem 283:13736-44
Khan, F S; Fujioka, M; Datta, P et al. (2008) The interaction of DIAP1 with dOmi/HtrA2 regulates cell death in Drosophila. Cell Death Differ 15:1073-83
Wu, A; Chen, J; Baserga, R (2008) Nuclear insulin receptor substrate-1 activates promoters of cell cycle progression genes. Oncogene 27:397-403
Yu, Je-Wook; Fernandes-Alnemri, Teresa; Datta, Pinaki et al. (2007) Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol Cell 28:214-27
Shi, Bin; Sepp-Lorenzino, Laura; Prisco, Marco et al. (2007) Micro RNA 145 targets the insulin receptor substrate-1 and inhibits the growth of colon cancer cells. J Biol Chem 282:32582-90

Showing the most recent 10 out of 49 publications