As more videos interviews are being uploaded to bhdsyndrome.org, we would like to introduce you to Dr Andrew Tee and his group at the Institute of Medical Genetics at Cardiff University’s School of Medicine. Their main focus involves tuberous sclerosis complex (TSC) and mTOR signalling in mammalian cells, and how its dysregulation can lead to cancer.
As discussed in a previous blog, the clinical similarities between BHD syndrome and TSC suggest that FLCN and the TSC proteins may function within a common pathway. Consequently, Dr Tee’s group in Cardiff are in an ideal position to bridge these fields in order to help elucidate the functions of FLCN and explain how its loss leads to BHD syndrome.
In particular, Research Fellow Dr Elaine Dunlop is studying mTOR signalling and its related pathways, and in recognition of this work she recently won the Third BHD Symposium poster prize for her study on ULK1 inhibition of mTORC1 signalling (Dunlop et al., 2011).
Additionally, as discussed in an earlier blog, work by PhD student Rachel Preston showed that HIF signalling also plays a role in BHD syndrome (Preston et al., 2010). This study will hopefully lead to many new avenues of research, and could also be used to help develop potential new therapies for BHD.
Dr Tee and his colleagues also collaborate extensively with numerous other research groups working on BHD syndrome around the world, and they hope to make use of next generation sequencing technologies to further their research in the near future.
To hear more about their BHD research and future plans, see our video interview with its accompanying transcript and audio-only file. Alternatively, the following publications may also be of interest and should give you an idea of the research currently being undertaken by this lab:
- Dunlop EA, Dodd KM, Land SC, Davies PA, Martins N, Stuart H, McKee S, Kingswood C, Saggar A, Corderio I, Medeira AM, Kingston H, Sampson JR, Davies DM, & Tee AR (2011). Determining the pathogenicity of patient-derived TSC2 mutations by functional characterization and clinical evidence. European journal of human genetics : EJHG.
- Dunlop EA, Hunt DK, Acosta-Jaquez HA, Fingar DC, & Tee AR (2011). ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding. Autophagy, 7 (7).
- Dunlop EA, & Tee AR (2009). Mammalian target of rapamycin complex 1: signalling inputs, substrates and feedback mechanisms. Cellular signalling, 21 (6), 827-35.
- Land SC, & Tee AR (2007). Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. The Journal of biological chemistry, 282 (28), 20534-43.
- Preston RS, Philp A, Claessens T, Gijezen L, Dydensborg AB, Dunlop EA, Harper KT, Brinkhuizen T, Menko FH, Davies DM, Land SC, Pause A, Baar K, van Steensel MA, & Tee AR (2011). Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility. Oncogene, 30 (10), 1159-73.
www.bhdsyndrome.org – the primary online resource for anyone interested in BHD Syndrome.