Drosophila lab studying organ size control, organ crosstalk and metabolism
We use the fruit fly Drosophila to study how organ size is maintained and how metabolism can shape organ growth.
- How differentiation is maintained in the developing nervous system
- How the niche surrounding the neural stem cells affects stem cell behaviour
- How one specialized cell type in the CNS can become another through trans-differentiation
- How regeneration is regulated in the CNSs of flies and zebrafish (in collaboration with Patricia Jusuf, UoM)
- How tumours breakdown fat and muscles during cachexia
- How organs communicate with each other to maintain tissue homeostasis
How do neurons maintain their specialised status?
The bidirectional conversion between differentiated cells and stem cells often underlies carcinogenesis. Mechanisms must be in place to prevent differentiated cells from reverting to multipotent stem cells. We have recently discovered that zinc finger transcription factor Nerfin-1 is required to maintain neurons in a differentiated state. In the absence of Nerfin-1, neurons rapidly increase their cellular growth and switch on stem cell markers, then form tumours. The lab is interested in identifying novel transcription factors that regulate this process, and investigate whether these factors are involved in regeneration. Related papers: Francesca Froldi, Milan Szuperak et al., G&D, 2015, Joep Vissers, Francesca Froldi et a., Cell Reports, 2018
How do dietary nutrients affect the ability of stem cells and stem cell-derived tumours to grow and divide?
The effect of diet on stem cell proliferation and tumour growth is poorly characterised. Using a chemically defined diet together with metabolomic approaches, we are interested in identifying metabolic alterations associated with dedifferentiation, stem cell reactivation and cancer. Related papers: Francesca Froldi, Milan Szuperak et al., G&D, 2015, Francesca Froldi et al., EMBO J, 2019
Lodge W#, Zavortink M#, Golenkina S# , Froldi F*, Dark C*, Cheung S, Parker BL, Blazev R, Bakopoulos D, Christie EL, Wimmer VC, Duckworth BC, Richardson HE, Cheng LY (2021) Tumor-derived MMPs regulate cachexia in a Drosophila cancer model. Dev Cell 2021 Aug 31;S1534-5807(21)00638-9. doi: 10.1016/j.devcel.2021.08.008.
Dong Q, Zavortink M, Froldi F, Golenkina S, Lam T, Cheng LY* (2021). Glial Hedgehog signalling and lipid metabolism regulate neural stem cell proliferation in Drosophila. EMBO Rep. 2021 May 5;22(5): Epub 2021 Mar 10. PMID: 33751817, https://pubmed.ncbi.nlm.nih.gov/33751817
Qian Dong and LY Cheng* (2020). Getting in shape: ATP pumps up the volume in Hh signalling. EMBO J. 2020 Nov 2;39(21):e106564. doi: 10.15252/embj.2020106564. Epub 2020 Oct 6.
Alvarez-Ochoa E, Froldi F, Cheng LY* (2020). Interorgan communication in development and cancer. Wiley Interdiscip Rev Dev Bio. 2020 Aug 27;e394. doi: 10.1002/wdev.394.
Froldi F, Pachnis P, Szuperak M, Costas O, Fernando T, Gould AP, Cheng LY* (2019). Histidine is selectively required for the growth of Myc-dependent dedifferentiation tumours in the Drosophila CNS. EMBO J. Apr 1;38(7)
Vissers JHA#, Froldi F#, Schroder J, Papenfuss AT, Cheng LY*, Harvey KF* (2018). The Scalloped and Nerfin-1 transcription factors cooperate to maintain neuronal cell fate. Cell Rep. Nov 6;25(6): 1561-1567 (# equal contribution, *Joint senior authors)
Poon CLC, Mitchell KA, Kondo S, Cheng LY*, Harvey KF* (2016). The Hippo pathway regulates neuroblasts and brain size in Drosophila melanogaster. Curr Biol. 26(8):1034-1042. (* Joint senior author)
Froldi F, Szuperak M, Weng CF, Shi W, Pappenfus T, Cheng LY (2015). The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells. Genes Dev. 29(2):129-143.
Cheng LY, Bailey AP, Leevers SJ, Ragan TJ, Driscoll PC, Gould AP (2011). Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila. Cell. 146(3):435–447.
Maurange C, Cheng L, Gould AP (2008). Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell. 133(5):891-902.