Future research project program

A) Fruit fly pupa. In the developing pupal legs (blue), small sections (white) allow confocal imaging for a long time (B,C). Within these regions, various systems display examples of tissue crowding, including sections of tarsal segments (pink) and joints (red). The sex comb is a rotating bristle row (yellow; arrow indicates comb rotation direction). t1 and t2 represent 1st and 2nd tarsal segment, respectively. Scale bar = 20 um. AP = After pupation.

Misregulation of cell turnover is believed to be at the heart of cancer formation, but the mechanisms that coordinately regulate cell loss and division are just beginning to be understood 1–3. Although contact inhibition is thought to regulate overall cell numbers within epithelia, cells constantly divide and die while retaining contacts with each other, so other factors must regulate the equilibrium between these two cell processes 4.

Recent work showed that under crowded cellular conditions, an increase in mechanical tension triggers cell extrusion 1,3,5. This suggests that modifications in this mechanism can lead to various epithelial pathologies and cancer 3,5. However, despite its potential application to understand early stages of cancer, this mechanism has only been studied in a few systems due to various technical impediments 1,3,5. I have pioneered the study of cell turnover in several new epithelial systems during my PhD and postdoctoral work, developing a successful research program mainly conducted by undergraduate students 6–8.

 

 

To see additional research projects…………………………………(To read more about it)

 

REFERENCES

  1. Eisenhoffer, G. T. et al. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature 484, 546–9 (2012).
  2. Marinari, E. et al. Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding. Nature 484, 542–5 (2012).
  3. Gudipaty, S., Lindblom, J., Loftus P., Redd, M., Edes, K., Davey, C. Krishnegowda, J., and Rosenblatt, J. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature 543, 118–121 (2017).
  4. Eisenhoffer, G. T. & Rosenblatt, J. Bringing balance by force: live cell extrusion controls epithelial cell numbers. Trends Cell Biol. 23, 185–192 (2014).
  5. Levayer, R., Dupont, C. & Moreno, E. Tissue Crowding Induces Caspase-Dependent Competition for Space. Curr. Biol. 26, 670–677 (2016).
  6. Malagón, J. N., Ahuja, A., Sivapatham, G., Hung, J. & Lee, J. Evolution of Drosophila sex comb length illustrates the inextricable interplay between selection and variation. Proc Nat Acad Sci 111, E4103–E4109 (2014).
  7. Malagon, J. & Larsen, E. Heredity and self-organization: partners in the generation and evolution of phenotypes. Int Rev Cell Mol Biol. 315, 153–181 (2015).
  8. Ma, X. et al. PP6 Disruption Synergizes with Oncogenic Ras to Report PP6 Disruption Synergizes with Oncogenic Ras to Promote JNK-Dependent Tumor Growth and Invasion. Cell Rep. 19, 2657–2664 (2017).
  9. Malagon, J. Sex combs in motion: Cellular processes involved in sex comb rotation in Drosophila melanogaster. (University of Toronto, 2013).