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
Research projects
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, Francesca Froldi et al., EMBO J, 2019
How do tumours grow at the expense of other tissues in cancer cachexia
Cancer cells are known to drive altered metabolic circuits to meet the bioenergetic and biosynthetic demands of increased cell growth and proliferation. Under nutrient restriction, when growth of most organs shut down, cancer cells can bypass these brakes imposed on cellular growth, thus gaining a growth advantage under these conditions. Furthermore, during cachexia, which causes more than one third of deaths in cancer patients, tumour derived factors can also induce the break down of fat and skeletal muscles, in order to generate metabolic intermediates necessary for the preferential tumour growth. The signalling between tumours and other tissues is highly complex, and the adaptations that allow cancer cells to preferentially activate growth are largely unknown. We seek to uncover novel mediators of cancer cachexia and investigate their mechanisms of action using Drosophila genetics, confocal microscopy, proteomics and metabolomics. We then seek to further this work by validating our findings in human samples. Related papers: Lodge et al., Dev Cell, 2021
People
Key publications
Dedifferentiation-derived neural stem cells exhibit perturbed temporal progression. Kellie Veen,, Phuong-Khanh Nguyen, Francesca Froldi, Qian Dong, Edel Alvarez-Ochoa, Kieran F. Harvey, John P D McMullen, Owen Marshall, Patricia R Jusuf, Louise Y Cheng, EMBO Reports, in press.
Non-autonomous regulation of neurogenesis by extrinsic cues: a Drosophila perspective Phuong-Khanh Nguyen, Louise Y Cheng, Oxford Open Neuroscience, Volume 1, 2022, kvac004, https://doi.org/10.1093/oons/kvac004
Analyzing cachectic phenotypes in the muscle and fat body of Drosophila larvae. Dark C, Cheung S, Cheng LY. STAR Protoc. 2022 Mar 9;3(1):101230. doi: 10.1016/j.xpro.2022.101230. eCollection 2022 Mar 18. PMID: 35284841
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.
