Cell death plays a central role in development and in many diseases. The research in my laboratory is focused on understanding the molecular mechanisms of programmed cell death and cell clearance. The model that we are using is the fruitfly Drosophila melanogaster, an organism with unique advantages in genetics and cell biology. A major interest of the lab is germline cell death, which can occur at several distinct stages in the fly ovary. The death of nurse cells in late oogenesis is developmentally programmed and occurs rapidly and synchronously in clusters as each oocyte develops. Germline cell death can also occur in response to starvation or other insults. While apoptosis is the major form of cell death occurring in response to starvation, a novel non-apoptotic type of cell death occurs during developmental nurse cell death.
The final step in programmed cell death is the removal of the corpse. Defective dead cell clearance is associated with auto-immune and neurodegenerative diseases in humans. In the fly ovary, “professional” phagocytes like macrophages are limited, and most of the cell clearance is carried out by epithelial follicle cells. Follicle cells synchronously engulf dying nurse cells, providing a powerful in vivo model system for investigating the genetics and cell biology of engulfment. We are also investigating cell clearance mechanisms by glia in the brain.
We are currently using genetic and molecular approaches to identify components of the cell death and cell clearance pathways in the ovary and the brain. Given the high degree of evolutionary conservation of known cell death mechanisms, we expect that pathways that we uncover in Drosophila will be conserved in humans.
- Yalonetskaya A, Mondragon AA, Hintze ZJ, Holmes S, McCall K (2019) Nuclear degradation dynamics in a non-apoptotic programmed cell death, Cell Death and Differentiation doi: 10.1038/s41418-019-0382-x.
- Mondragon AA, Yalonetskaya A, Ortega AJ, Zhang Y, Naranjo O, Elguero J, Chung W-S, McCall K (2019) Lysosomal machinery drives extracellular acidification to direct non-apoptotic cell death Cell Reports 27: 11-19.
- Santoso CS, Meehan TL, Peterson JS, Cedano TM, Turlo CV and McCall K (2018) The ABC transporter Eato promotes cell clearance in the Drosophila melanogaster ovary. G3: Genes, Genomes, Genetics. doi.org/10.1534/g3.117.300427.
- Serizier, S.B. and McCall, K (2017) Scrambled eggs: apoptotic cell clearance by non-professional phagocytes in the Drosophila ovary. Frontiers in Immunology. doi.org/10.3389/fimmu.2017.01642.
- Etchegaray JI, Elguero EJ, Tran J, Sinatra V, Feany MB, and McCall K (2016) Defective phagocytic corpse processing results in neurodegeneration and can be rescued by TORC1 activation, Journal of Neuroscience 36: 3170-83.
- Timmons AK, Mondragon AA, Schenkel CE, Taylor JD, Moynihan KE, Etchegaray JI, Meehan TL, and McCall K (2016) Phagocytosis genes non- autonomously promote developmental cell death in the Drosophila ovary, Proceedings of the National Academy of Sciences USA 113: E1246-55.
- Meehan TL, Kleinsorge S, Timmons AK, Taylor J, and McCall K (2015) Polarization of the epithelial layer and apical localization of integrins are required for engulfment of apoptotic cells, Disease Models and Mechanisms 8: 1603-1614.
- Etchegaray JI, Timmons A, Klein AP, Pritchett TL, Welch E, Meehan TL, Li C, McCall K (2012) Draper acts through the JNK pathway to control synchronous engulfment of dying germline cells by follicular epithelial cells, Development 139: 4029-4039.
- BI 572 Advanced Genetics