The long-term goal of this project is to determine the mechanism(s) by which autophagy contributes to tumor development, maintenance, and treatment. We will assess the role of autophagy in Myc-induced lymphoma development and maintenance. Beclin, a gene required for autophagy, is monoallelically deleted in approximately 70% of breast cancers and heterozygous deletion of Beclin leads to tumor development. Beclin heterozygosity can also co-operate with c-Myc over expression to increase the rate of tumor development (see preliminary data). This grant focuses on the role of autophagy in Myc-induced B-cell lymphoma.
Specific aim 1 will further characterize the role of autophagy as a checkpoint in cancer development and determine its role in the cell cycle and apoptotic functions attributed to Myc overexpression.
Specific aim 2 will address whether or not a minimal level of autophagy is required for tumor maintenance. It is suggested that a complete ablation of autophagy may be theraputic, and we will test this hypothesis genetically. ? ? ? ?
|Ouellette, Scot P; Dorsey, Frank C; Moshiach, Simon et al. (2011) Chlamydia species-dependent differences in the growth requirement for lysosomes. PLoS One 6:e16783|
|Joo, Joung Hyuck; Dorsey, Frank C; Joshi, Aashish et al. (2011) Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy. Mol Cell 43:572-85|
|Steeves, Meredith A; Dorsey, Frank C; Cleveland, John L (2010) Targeting the autophagy pathway for cancer chemoprevention. Curr Opin Cell Biol 22:218-25|
|Dorsey, Frank C; Rose, Kristie L; Coenen, Silvia et al. (2009) Mapping the phosphorylation sites of Ulk1. J Proteome Res 8:5253-63|