Current Research

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.

Selected Publications

  • Elguero JE, Liu G, Tiemeyer K, Bandyadka S, Gandevia H, Duro L, Yan Z, McCall K (2023). Defective phagocytosis leads to neurodegeneration through systemic increased innate immune signaling, iScience 12:108052.
  • Serizier SB, Peterson JS and McCall K (2022). Non-autonomous cell death induced by the Draper phagocytosis receptor requires signaling through the JNK and Src pathways, Journal of Cell Science 35:jcs250134.
  • Lebo DPV and McCall K (2021). Murder on the ovarian express, a tale of non-autonomous cell death in the Drosophila ovary, Cells 10:1454.
  • Lebo DPV, Chirn A, Taylor J, Levan A, Doerre Torres V , Agreda E, Serizier SB, Lord A, Jenkins VK, and McCall K (2021). An RNAi screen of the kinome in epithelial follicle cells of the Drosophila melanogaster ovary reveals genes required for proper germline death and clearance, G3: Genes, Genomes, Genetics 11:jkaa066.
  • Yalonetskaya A, Mondragon AA, Hintze ZJ, Holmes S, McCall K (2020). Nuclear degradation dynamics in a non-apoptotic programmed cell death, Cell Death and Differentiation 27:711-724.
  • 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.
  • 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.

Courses Taught:

  • BI 572 Advanced Genetics
  • BI 576 Carcinogenesis

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