Dr Ferran Valderrama is the principal investigator of the Prostate Cancer Cell Biology Laboratory and the academic director of the Image Resource Facility at St George’s. He is a senior lecturer in Anatomy and Coordinator of the Anatomy Demonstrator Programme.
Dr Valderrama’s laboratory has developed a 3D cell model that recapitulates the morphogenesis of the glandular units that constitute the prostate – known as acini. Using this model, his lab is investigating the mechanisms of prostate cancer progression and the role of cell migration in this process, with particular interest in the role of the ERM and Cadherin family of proteins.
Prostate cancer (PC) is one of the leading causes of cancer death, carrying the second highest male cancer mortality rate in the UK (Cancer Research UK, 2010). PC originates from early lesions in their acini - the glandular structures of the prostate. These alterations are characterized by intraluminal hyperproliferation – high rate of cell division in the inside cavity – of the acini. Therefore, identification of factors altering the epithelial organization of acini - leading to intraluminal proliferation - may represent a strategy to determine the causes of prostate cancer progression.
The 3D cellular model Dr Valderrama’s lab has established monitors morphogenesis of prostate acinar-like structures using microscopy techniques. With this model the group aims to identify the molecular factors that would lead to PC.
Two main areas of research are currently ongoing in the laboratory - firstly, the role of cell migration in prostate cancer. ERM and Cadherins are two families of proteins that play a relevant role in cell-cell and cell-substrate interactions, processes that are altered during prostate cancer progression. The lab is interested in investigating the role of these families of proteins during the migration and invasion observed during prostate cancer progression. The group also aims to investigate the reciprocal effects of the stromal environment on PC cells and how this affects migration and invasion.
Secondly, the lab are working on patient stratification. The outcome that prostate cancer treatment has in patient survival is not optimal. This is due to the inability to consistently distinguish aggressive prostate cancer from indolent disease, which leads to inappropriate treatment and high morbidity and mortality. Therefore, uncovering molecular events in PC aiming to develop methods that facilitate patient stratification is paramount. Using their 3D acini model, Dr Valderrama’s lab is developing methods which aim to bring objective measurements for the grade of the disease, which could complement the current clinical classification of patients diagnosed with prostate cancer
Dr Valderrama joined the Division of Biomedical Sciences in November 2009 and is currently a member of the Biomedical Sciences Research Centre.
Dr Valderrama obtained his PhD in Cell and Molecular Biology under the supervision of Professor Gustavo Egea studying Intracellular membrane dynamics, where his studies established for the first time the presence of actin microfilaments in COP-I vesicles derived from the Golgi complex.
During his postdoctoral training – when he was awarded a European Union-Marie Curie Postdoctoral fellowship - Dr Valderrama first joined the laboratory of Dr Michael Way at the European Molecular Biology Laboratories (EMBL) in Heidelberg (Germany) and later on at the London Research Institute (LRI-CRUK) in London (UK). Of interest, amongst the investigations carried on during that period is the identification of a vaccinia virus (a relative of the smallpox causative virus) protein able to induce migration of the host cells upon infection. Subsequently, Dr Valderrama moved to the laboratory of Professor Anne Ridley first at the Ludwig Institute for Cancer Research and subsequently at the Randall Institute in King’s College London, where he studied the role of the Ezrin-Radixin-Moesin (ERM) family of proteins - involved in the regulation of the interface between the actin cytoskeleton and the plasma membrane - during migration of prostate cancer cells.
Brown L, Waseem A, Cruz IN, Szary J, Gunic E, Mannan T, Unadkat M, Yang M, Valderrama F, O Toole EA, Wan H. (2013). Desmoglein 3 promotes cancer cell migration and invasion by regulating activator protein 1 and protein kinase C-dependent-Ezrin activation. Oncogene doi:10.1038/onc.2013.186.
Reymond N, Im JH, Garg R, Vega FM, Borda d'Agua B, Riou P, Cox S, Valderrama F, Muschel RJ and Ridley AJ (2012). Cdc42 promotes transendothelial migration of cancer cells through β1 integrin. J Cell Biol, 199(4), 653-668. doi:10.1083/jcb.201205169.
Valderrama F, Thevapala S and Ridley AJ (2012). Radixin regulates cell migration and cell-cell adhesion through Rac1. J Cell Sci, 125(Pt 14), 3310-3319. doi:10.1242/jcs.094383.
Wojtala RL, Tavares IA, Morton PE, Valderrama F, Thomas NS and Morris JD (2011). Prostate-derived sterile 20-like kinases (PSKs/TAOKs) are activated in mitosis and contribute to mitotic cell rounding and spindle positioning. J Biol Chem, 286(34), 30161-30170. doi:10.1074/jbc.M111.228320.
Valderrama F and Ridley AJ (2008). Getting invasive with GEP100 and Arf6. Nat Cell Biol, 10(1), 16-18. doi:10.1038/ncb0108-16
Valderrama F, Cordeiro JV, Schleich S, Frischknecht F and Way M (2006). Vaccinia virus-induced cell motility requires F11L-mediated inhibition of RhoA signaling. Science, 311(5759), 377-381. doi: 10.1126/science.1122411
Krause M, Leslie JD, Stewart M, Lafuente EM, Valderrama F, Jagannathan R, Strasser GA, Rubinson DA, Liu H, Way M, Yaffe MB, Boussiotis VA and Gertler FB (2004). Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics. Dev Cell, 7(4), 571-583. doi:10.1016/j.devcel.2004.07.024.
Valderrama F, Luna A, Babia T, Martinez-Menarguez JA, Ballesta J, Barth H, Chaponnier C, Renau-Piqueras J and Egea G. (2000). The golgi-associated COPI-coated buds and vesicles contain beta/gamma -actin. Proc Natl Acad Sci U S A, 97(4), 1560-1565.
Ms Jarama Clucas (PhD student – St George's PhD programme): Jazz aims to investigate the role of the ERM proteins in the morphogenesis and disruption of prostate acini and how this would affect prostate cancer progression.
Mr Behnam Tahmassebypour (visiting student / part time technician): Behnam aims to investigate the role of Cadherins (in particular E- and N-cadherin) during the early events that lead to prostate cancer.
Mr Antoni Olona (visiting student): Toni is investigating the role of the RhoGTPase family of proteins in the regulation of the activity of ERM proteins and how this regulation might affect prostate cancer progression.
Professor Guy Whitley: Effect of Angiogenesis in prostate cancer (PC) tumour formation; Role of ERM proteins in trophoblast invasion.
Dr Francesc Miralles: Role of ERM proteins in skeletal muscle. cells.
Dr Tristan McKay: Tumour hypoxia signalling in PC.
Dr Catherine Corbishley - St George’s University Hospitals NHS Foundation Trust
Professor Peter Parker (Cancer Research UK - London Research Institute/Cancer Division Kings College London)
Professor Harry Mellor (University of Bristol)
Professor Freddie Hamdy and Dr Richard Bryant (Nuffield Department of Surgical Sciences – University of Oxford)
Development and characterisation of a multichannel micro-plate for the analysis of 3-dimensional cell migration, award from the Centre for Enterprise and Innovation (St George's, University of London), principal investigator, December 2010 to June 2011, £14,400.
Start-up grant, St George's, principal investigator, January 2010 to January 2012, £25,000
Role of ERM proteins in cancer cell invasion, Cancer Research UK, Co-investigator with Professor Anne Ridley, January 2006 to January 2009, £180,000.
Dr Valderrama lectures Biomedical Science BSc (Hons) students on the cell nucleus, the cytoskeleton, an introduction to microscopy and gives student-based learning tutorials.
As part of SGUL's Medicine MBBS degrees Dr Valderrama is coordinator of the Anatomy Demonstrator Programme. He gives anatomy lectures and dissection room practical sessions He is also responsible for Student Selected Component (SSC) tutorials and is an SSC examiner for transition year students.
Dr Valderrama lectures and is responsible for tutorials on the Pharmacy MPharm (Hons) course (run jointly by Kingston University and St George's) and the Biomedical Science MRes course.
Dr Valderrama is also an undergraduate personal tutor and supervisor.
At postgraduate level as part of the MRes Biomedical Sciences course Dr Valderrama lectures and gives tutorials. He also supervises student projects on this course.