Studies on the regulation of cell proliferation and growth are important to our understanding of developmental biology and tumorigenesis. The long-term goal of the proposed research is to investigate the molecular mechanisms that regulate cell proliferation and growth. In order to address this question, the investigators will analyze the Tsc1 and Tsc2 tumor suppressor genes as well as genes interacting with them in the developing imaginal tissues of Drosophila melanogaster. Mutations in either TSC1 or TSC2 result in a hereditary disease - tuberous sclerosis. The disease occurs in 1/6000 births and is characterized by benign neoplasms known as hamartomas, in multiple organs. Tsc1 and Tsc2 are functionally conserved from flies to humans. The investigators have previously shown that Tsc1 and Tsc2 function together in the Insulin/PI3K/Akt signaling pathway, downstream of Akt and upstream of S6K. Tsc1, Tsc2, and other upstream components of the pathway affect both cell proliferation and growth, however S6K only affects cell growth. The mechanism by which Tsc1 and Tsc2 regulate cell proliferation is not yet known. The investigators propose to investigate the mechanism by which cell proliferation is regulated by Tsc1 and Tsc2. Specifically, the investigators propose to identify Tsc1/Tsc2 interacting genes by performing genetic modifier screens and by using microarray to identify genes regulated by Tsc1/Tsc2. The investigators will then select several Tsc1/Tsc2 interacting genes and further characterize the interaction between these identified candidate genes and Tsc1/Tsc2 as well as their role in the regulation of cell proliferation. This application for the mentored K08 award is submitted so as to enable the candidate to gain necessary didactic and scientific training in developmental and molecular genetics. The eventual goal is to independently investigate molecular mechanisms underlying human disease and develop targeted therapeutic strategy utilizing model organisms.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD044706-03
Application #
6903424
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Coulombe, James N
Project Start
2003-07-24
Project End
2008-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$128,814
Indirect Cost
Name
Yale University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520