WORLD CLASS BASIC, TRANSLATIONAL AND CLINICAL RESEARCH

Introduction

Prostate cancer is a very heterogeneous disease both clinically and biologically. New therapies have produced some clinical successes, but a subset of patients progress to incurable castration-resistant PCa (CRPC) and it is not yet possible to predict which patients will respond best to which treatment.

The initiation of CRPC and metastatic dissemination likely involves the existence of tumour cells, so called cancer-initiating or propagating cells, with the ability to self-renew, survive anti-tumoural treatment effect and interact with the niche to promote daughter cells growth to recapitulate the heterogeneity of the tumour of origin. Despite the number of mutations, recent evidences suggest a key role cell of origin and their reprogrammed niche for the progression of the disease. By combining conditional mouse models, primary cell 3D culture (human and mouse), and genomics, we aim to characterise the molecular pathways that regulate tumour-initiating/propagating cells, which are responsible of tumour recurrence, to develop novel therapeutics that tackle the residual disease.

Selected Publications

Mevel R, Steiner I, Mason S, Galbraith LC, Patel R, Fadlullah MZ, Ahmad I, Leung HY, Oliveira P, Blyth K, Baena E, Lacaud G. (2020)
RUNX1 marks a luminal castration-resistant lineage established at the onset of prostate development.
Elife 9:e60225. PubMed abstract

Murphy RG, Roddy AC, Srivastava S, Baena E, Waugh DJ, M O'Sullivan J, McArt DG, Jain S, LaBonte MJ. (2020)
Prostate cancer heterogeneity assessment with multi-regional sampling and alignment-free methods. 
NAR Genom Bioinform. 2(3):lqaa062. PubMed abstract

Parry MA, Srivastava S, Ali A, Cannistraci A, Antonello J, Barros-Silva JD, Ubertini V, Ramani V, Lau M, Shanks J, Nonaka D, Oliveira P, Hambrock T, Leong HS, Dhomen N, Miller C, Brady G, Dive C, Clarke NW, Marais R, Baena E. (2019)
Genomic evaluation of multiparametric magnetic resonance imaging-visible and -nonvisible lesions in clinically localised prostate cancer.
European Urology Oncology 2(1):1-11. PubMed abstract

Barros-Silva JD, Linn DE, Steiner I, Guo G, Ali A, Pakula H, Ashton G, Peset I, Brown M, Clarke NW, Bronson RT, Yuan GC, Orkin SH, Li Z, Baena E. (2018)
Single-cell analysis identifies LY6D as a marker linking castration-resistant prostate luminal cells to prostate progenitors and cancer.
Cell Reports 25(12):3504-3518. PubMed abstract

Wang P, Dreger M, Madrazo E, Williams CJ, Samaniego R, Hodson NW, Monroy F, Baena E, Sánchez-Mateos P, Hurlstone A, Redondo-Muñoz J. (2018)
WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment.
Proc Natl Acad Sci U S A [Epub 9 July] PubMed abstract

Ali A, Hoyle A, Baena E, Clarke NW. (2017)
Identification and evaluation of clinically significant prostate cancer: a step towards personalized diagnosis.
Current Opinion in Urology 27(3):217-224. PubMed abstract

Baena E, Shao Z, Linn DE, Glass K, Hamblen MJ, Fujiwara Y, Kim J, Nguyen M, Zhang X, Godinho FJ, Bronson RT, Mucci LA, Loda M, Yuan GC, Orkin SH, Li Z. (2013)
ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients.
Genes & Development 27(6):683-98. PubMed abstract

Vallespinós M, Fernández D, Rodríguez L, Alvaro-Blanco J, Baena E, Ortiz M, Dukovska D, Martínez D, Rojas A, Campanero MR, Moreno de Alborán I. (2011)
B Lymphocyte commitment program is driven by the proto-oncogene c-Myc.
Journal of Immunology 186(12):6726-36. PubMed abstract

Baena E, Ortiz M, Martínez-A C, de Alborán IM. (2007)
c-Myc is essential for hematopoietic stem cell differentiation and regulates Lin(-)Sca-1(+)c-Kit(-) cell generation through p21.
Experimental Hematology 35(9):1333-43. PubMed abstract

Baena E, Gandarillas A, Vallespinós M, Zanet J, Bachs O, Redondo C, Fabregat I, Martinez-A C, de Alborán IM.(2005)
c-Myc regulates cell size and ploidy but is not essential for postnatal proliferation in liver.
Proc Natl Acad Sci U S A 102(20):7286-91. PubMed abstract

Scientific Officer
Pengbo Wang

Postdoctoral Fellow
Valentina Ubertini

Graduate Student
Ivana Steiner
Alexander Du Feu

ERASMUS Student
Silvia D’Ambrosi