Autophagy is a cellular catabolic process through which cytoplasmic materials are targeted for lysosomal degradation via a series of intracellular vesicular formation and fusion events. After lysosomal degradation, biological bulding blocks and energy can be recycled to maintain essential cellular activity. Autophagy is required for various biological processes and is closely associated with a number of human diseases including cancer. The long-term goal of this proposal is to understand the molecular basis of autophagy in mammalian cells and to dissect the role of autophagy in cancer. Specifically, in this proposal I will (1) determine the molecular mechanisms by which LRRFIP1, a novel autophagic protein I recently identified, regulates autophagy;and (2) investigate the role of autophagy in cancer development and treatment by using an RCAS-tva based mouse model for glioblastoma. To achieve these goals, a combination of biochemical, cellular and molecular biological, and animal modelling techniques will be used. Success of this study will not only lead to the understanding of novel molecular mechanisms underlying mammalian autophagy, but will also provide insights into development of novel cancer therapeutic approaches that target autophagy.

Public Health Relevance

Success of this study will not only lead to the understanding of novel molecular mechanisms underlying mammalian autophagy, but will also provide insights into development of novel cancer therapeutic approaches that target autophagy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA162691-02
Application #
8653420
Study Section
Special Emphasis Panel (ZRG1-F09-E (20))
Program Officer
Jakowlew, Sonia B
Project Start
2012-01-01
Project End
2013-09-30
Budget Start
2013-01-01
Budget End
2013-09-30
Support Year
2
Fiscal Year
2013
Total Cost
$42,794
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Gammoh, Noor; Florey, Oliver; Overholtzer, Michael et al. (2013) Interaction between FIP200 and ATG16L1 distinguishes ULK1 complex-dependent and -independent autophagy. Nat Struct Mol Biol 20:144-9
Gammoh, Noor; Lam, Du; Puente, Cindy et al. (2012) Role of autophagy in histone deacetylase inhibitor-induced apoptotic and nonapoptotic cell death. Proc Natl Acad Sci U S A 109:6561-5