Caroline Hill

Developmental Signalling Laboratory

The research in my lab is focused on understanding how cells communicate with their environment and with each other using extracellular signals that induce new programmes of gene expression and regulate cell behaviour.

This phenomenon underpins embryonic development and tissue homeostasis in adult organisms, and its misregulation can cause human diseases, the most widespread being cancer.

The work in the laboratory focuses on the Transforming Growth Factor β (TGF-β) superfamily, a group of growth and differentiation factors comprising the TGF-βs, 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-β, BMP and Nodal signalling occurs in cancer, and is important for both primary tumour formation and for metastasis.

Our goal is to understand the mechanism whereby these ligands signal from the plasma membrane to the nucleus and how they regulate transcription of target genes via activated complexes of Smad proteins. We want to determine how they function and are regulated during embryonic development, and how their activity is perturbed in cancer.

To do this we use the powerful combination of early vertebrate developmental systems (zebrafish and Xenopus embryos) with tissue culture systems and mouse tumour models. We use methodologies ranging from molecular, cell and developmental biology to computational modelling. We anticipate that our work will lead to diagnostic and prognostic markers for cancer and eventually to new cancer therapies.

 

TGF-β superfamily ligand.

TGF-β superfamily ligand. A general scheme for TGF-superfamily signalling pathways, which are studied in the Hill lab in both early vertebrate development systems (zebrafish and Xenopus) and in tissue culture systems. (Click to view larger image)

Selected publications

Gaarenstroom, T, Hill, CS. TGF-β signaling to chromatin: How Smads regulate transcription during self-renewal and differentiation. Semin Cell Dev Biol. 2014 32; 107-118. 

Harding JL, Horswell S, Heliot C, Armisen J, Luscombe NM, Zimmerman LB, Miska EA, Hill CS. Small RNA profiling of Xenopus embryos reveals novel miRNAs and a new class of small RNAs derived from intronic transposable elements. Genome Res. 2013 24; 96-106. 

Reichert S, Randall, RA, Hill CS. A BMP regulatory network controls ectodermal cell fate decisions at the neural plate border. Development. 2013 140; 4435-44.

Ramel MC, Hill CS. The ventral to dorsal BMP activity gradient in the early zebrafish embryo is determined by graded expression of BMP ligands. Dev Biol. 2013 378; 170-182. 

Vizán P, Miller DS, Gori I, Das D, Schmierer B, Hill CS. Controlling Long-Term Signaling: Receptor Dynamics Determine Attenuation and Refractory Behavior of the TGF-β Pathway. Sci Signa. 2013; 6(305):ra106 

Wakefield, LM, Hill, CS. Beyond TGFβ: roles of other TGFβ superfamily members in cancer. Nat Rev Cancer . 2013 13; 328-41.

Agricola E, Randall RA, Gaarenstroom T, Dupont S, Hill CS. Recruitment of TIF1γ via its PHD finger-bromodomain to histone H3 tails activates its E3 ubiquitin ligase and transcriptional repressor activities. Mol. Cell. 2011 43; 85-96 

Wu MY, Ramel MC, Howell M, Hill CS. SNW1 Is a Critical Regulator of Spatial BMP Activity, Neutral Plate Border Formation, and Neural Crest Specification in Vertebrate Embryos. PLoS Biol. 2011 9(2); e1000593 

Schmierer B, Tournier AL, Bates PA, Hill CS. Mathematical modelling identifies Smad nucleocytoplasmic shuttling as a dynamic signal-interpreting system. Proc. Natl. Acad. Sci. USA. 2008 105; 6608-6613 

Levy L, Howell M, Das D, Harkin S, Episkopou V, Hill CS. Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Mol. Cell. Biol. 2007 27; 6068-6083 

Ross S, Cheung E, Howell M, Petrakis TG, Kraus WL, Hill,CS. Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription. EMBO J. 2006 25; 4490-4502 

Inman GI, Nicolás FJ, Hill CS. Nucleocytoplasmic shuttling of Smads 2, 3 and 4 permits sensing of TGF- receptor activity. Mol. Cell. 2002 10; 283-294. (Highlight published in Nature Reviews Molecular Cell Biology. October 2002 p.728. Two-way Traffic) 

Germain S, Howell M, Esslemont GM, Hill CS. Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif. Genes Dev. 2000 14; 435-451

Caroline Hill

caroline.hill@crick.ac.uk
+44 (0)20 379 61251

  • Qualifications and history
  • 1989 PhD, Cambridge University, UK
  • 1991 Postdoctoral Research Fellow, Imperial Cancer Research Fund, UK
  • 1995 Established lab at Ludwig Institute for Cancer Research, UCL Branch, UK
  • 1998 Moved lab to the Imperial Cancer Research Fund, UK (in 2002 the Imperial Cancer Research Fund became Cancer Research UK)
  • 2015 Group Leader, the Francis Crick Institute, London, UK