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ZFIN ID: ZDB-LAB-110602-1
Hill Lab
PI/Director: Hill, Caroline
Co-PI / Senior
Das, Debipriya
Kingston, Isabel
Randall, Becky
Contact Person: Hill, Caroline
Address: The Francis Crick Institute Lincoln's Inn Fields Laboratory 44 Lincoln's Inn Fields London WC2A 3LY UK
Country: United Kingdom
Phone: + 44 20 7269 2941
Fax: + 44 20 7269 3093
Line Designation: fci

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The work of Caroline Hill’s laboratory focuses on the Transforming Growth Factor beta (TGF-beta) superfamily, a group of growth and differentiation factors comprising the TGF-betas, Activins, Nodals, BMPs and GDFs. These ligands play critical roles during early vertebrate development in the specification and subsequent patterning of the germ layers, and deregulation of TGF-beta, BMP and Nodal signalling has been implicated in cancer.

Caroline Hill and her co-workers want to understand how these pathways function normally in early vertebrate development and in adult untransformed tissue culture cells, and how these signalling pathways are perturbed in cancer. They have been exploiting the very powerful combination of early Xenopus laevis and zebrafish embryos, together with a variety of model tissue culture systems, and have used methodologies ranging from developmental and cell biology to computational modelling. Their goal is to understand the mechanism by which signals from receptors for TGF-beta superfamily members are transduced to the nucleus and how this leads to regulation of transcription of target genes. They are defining what molecules are involved and how they act and elucidating how the pathways are regulated. They want to know in particular how parameters such as cell type, signalling context, and signal intensity and duration, contribute to shaping the biological response to TGF-beta superfamily ligands. They also aim to understand how TGF-beta signalling contributes to cancer, in particular how it acts as a tumour suppressor and a tumour promoter, and how it might switch between these two behaviours as tumours progress. They want to be able to use this knowledge to determine how the tumour promoting effects of TGF-beta can specifically be inhibited for therapeutic ends and to develop useful biomarkers for the diagnosis and prognosis of cancer.

Briones-Orta, Marco Post-Doc van Boxtel, Thijs Post-Doc Vizan, Pedro Post-Doc
Gaarenstroom, Tessa Graduate Student Harding, Joanne Graduate Student Reichert, Sabine Graduate Student

Reichert, S., Pavón Arocas, O., Rihel, J. (2019) The Neuropeptide Galanin Is Required for Homeostatic Rebound Sleep following Increased Neuronal Activity. Neuron. 104(2):370-384.e5
van Boxtel, A.L., Economou, A.D., Heliot, C., Hill, C.S. (2017) Long-Range Signaling Activation and Local Inhibition Separate the Mesoderm and Endoderm Lineages. Developmental Cell. 44(2):179-191.e5
Chen, S., Reichert, S., Singh, C., Oikonomou, G., Rihel, J., Prober, D.A. (2017) Light-Dependent Regulation of Sleep and Wake States by Prokineticin 2 in Zebrafish. Neuron. 95(1):153-168.e6
van Boxtel, A.L., Chesebro, J.E., Heliot, C., Ramel, M.C., Stone, R.K., Hill, C.S. (2015) A Temporal Window for Signal Activation Dictates the Dimensions of a Nodal Signaling Domain. Developmental Cell. 35:175-185
Reichert, S., Randall, R.A., and Hill C.S. (2013) A BMP regulatory network controls ectodermal cell fate decisions at the neural plate border. Development (Cambridge, England). 140(21):4435-4444
Ramel, M.C., and Hill, C.S. (2013) The ventral to dorsal BMP activity gradient in the early zebrafish embryo is determined by graded expression of BMP ligands. Developmental Biology. 378(2):170-82
Sanvitale, C.E., Kerr, G., Chaikuad, A., Ramel, M.C., Mohedas, A.H., Reichert, S., Wang, Y., Triffitt, J.T., Cuny, G.D., Yu, P.B., Hill, C.S., and Bullock, A.N. (2013) A New Class of Small Molecule Inhibitor of BMP Signaling. PLoS One. 8(4):e62721
Wu, M.Y., Ramel, M.C., Howell, M., and Hill, C.S. (2011) SNW1 Is a Critical Regulator of Spatial BMP Activity, Neural Plate Border Formation, and Neural Crest Specification in Vertebrate Embryos. PLoS Biology. 9(2):e1000593
Batut, J., Howell, M., and Hill, C.S. (2007) Kinesin-mediated transport of smad2 is required for signaling in response to tgf-Beta ligands. Developmental Cell. 12(2):261-274
Dorey, K., and Hill, C.S. (2006) A novel Cripto-related protein reveals an essential role for EGF-CFCs in Nodal signalling in Xenopus embryos. Developmental Biology. 292(2):303-316
Randall, R.A., Germain, S., Inman, G.J., Bates, P.A., and Hill, C.S. (2002) Different Smad2 partners bind a common hydrophobic pocket in Smad2 via a defined proline-rich motif. The EMBO journal. 21(1-2):145-156