Cell growth, division, and death are determinants of tissue and animal size, and defects in these fundamental cellular processes result in a variety of human disorders including cancer. The mechanistic relationship between growth and cell death is poorly defined in the context of normal animal development even though they have been the focus of many studies. Apoptosis and autophagic cell death are the two most prominent morphological forms of programmed cell death that occur during development. We are studying steroid-activated autophagic programmed cell death during development of the fruit fly Drosophila melanogaster using larval salivary gland cell death as a model. An increase in steroid triggers a genetic hierarchy that activates nearly synchronous cell death in salivary glands. These developmentally-regulated cell deaths utilize apoptosis genes including caspase proteases, but salivary glands also possess the morphology of cells that die-by autophagic cell death. Mutations in caspases only partially inhibit salivary gland cell death, and our recent studies suggest an important relationship between steroid signaling, growth that is regulated by phosphoinositide 3 kinase (PI3K), and death of this tissue. Here we propose to: (1) determine the relationship between salivary gland growth and autophagic cell death during development, (2) determine how PI3K-induced growth influences steroid signaling and cell destruction mechanisms in dying salivary glands, and (3) identify new genes that function in autophagic cell death. The recent association of autophagic cell death with neurodegenerative disorders and cancer indicates the importance of investigating this understudied form of programmed cell death. ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BDA-F (02))
Program Officer
Zatz, Marion M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Massachusetts Medical School Worcester
Schools of Medicine
United States
Zip Code
Velentzas, Panagiotis D; Zhang, Lejie; Das, Gautam et al. (2018) The Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death. Dev Cell 47:281-293.e4
Zhao, Shaowei; Fortier, Tina M; Baehrecke, Eric H (2018) Autophagy Promotes Tumor-like Stem Cell Niche Occupancy. Curr Biol 28:3056-3064.e3
Lin, Lin; Rodrigues, Frederico S L M; Kary, Christina et al. (2017) Complement-Related Regulates Autophagy in Neighboring Cells. Cell 170:158-171.e8
Anding, Allyson L; Baehrecke, Eric H (2017) Cleaning House: Selective Autophagy of Organelles. Dev Cell 41:10-22
Lee, T V; Kamber Kaya, H E; Simin, R et al. (2016) The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila. Cell Death Differ 23:1555-64
Tracy, Kirsten; Velentzas, Panagiotis D; Baehrecke, Eric H (2016) Ral GTPase and the exocyst regulate autophagy in a tissue-specific manner. EMBO Rep 17:110-21
Lindqvist, L M; Simon, A K; Baehrecke, E H (2015) Current questions and possible controversies in autophagy. Cell Death Discov 1:
Zhang, Hong; Baehrecke, Eric H (2015) Eaten alive: novel insights into autophagy from multicellular model systems. Trends Cell Biol 25:376-87
Anding, Allyson L; Baehrecke, Eric H (2015) Autophagy in Cell Life and Cell Death. Curr Top Dev Biol 114:67-91
Galluzzi, Lorenzo; Pietrocola, Federico; Bravo-San Pedro, José Manuel et al. (2015) Autophagy in malignant transformation and cancer progression. EMBO J 34:856-80

Showing the most recent 10 out of 43 publications