We use the fruit fly Drosophila to study how organ size is maintained and how metabolism can shape organ growth.
We are interested in a number of questions:
- How differentiation is maintained in the developing nervous system
- How the niche surrounding the neural stem cells affect 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
- 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 (Froldi et al., 2015). 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.
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.
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.
PhD and postdoc positions are available in the areas of research outlined above. Please contact Louise Cheng for further information.