Research

Area 5

Human and experimental functional oncomorphology.

Team leader

Strategic objectives

  1. Identification of genetic and molecular mechanisms implicated in the development and progression of human neoplasms.
  2. Development of strategies for transferring to clinical practice the knowledge generated by basic research on human tumors. Identification of parameters allowing the improved diagnosis and prognosis of neoplastic disease, and the identification of possible therapeutic targets

Main lines of research

  1. Lymphoid neoplasms
    a) Study of the alterations of the molecular mechanisms related to the cell cycle, genomic instability and the transcriptional expression profiles involved
    in the development and progression of these tumors as biomarkers of clinicopathological relevance.
    b) Functional study of molecular factors that may contribute to tumor pathogenesis, and which therefore may be candidates for the development of novel guided treatment strategies.
  2. Solid neoplasms
    a) Study of the molecular mechanisms of invasion and metastasis, transcriptional expression profiles implicated in the development and progression of different human tumors
    in relation to development, biological aggressivity (adhesion molecules) and therapeutic options. We focus mainly on breast and prostate tumors as neoplasms under
    hormone influence, and urological tumors and airway neoplasms – including head and neck tumors.
    b) Study of the possible criteria of treatment response and prognosis in neurological tumors.

Grups

Molecular pathology of solid tumors (Associated)

FERNANDEZ, PEDRO LUIS

(CDB)

The group studying the progression of solid neoplasms has continued with the analysis of different tumor types, including urological, breast, neurological and head and neck neoplasms. In reference to prostate cancer, mention may be made of the investigation of practical applications of its genetic signature, based on the analysis of surplus biopsy material. Different potential partners in the industry have been contacted to this effect. In addition, in collaboration with the group of Dr. Thomson, or the IBM-CSIC in Barcelona, studies have been of cellular models of prostate cancer with different aggressivity profiles and phenotypes, and which are being extended to “in vivo” studies in mice. In breast cancer, analyses have been made of the transcriptional profiles of primary infiltrating ductal carcinomas and their lymph node metastases, which have allowed us to define genetic signatures of disease progression and potential metabolic pathways affected by them in the early metastatic process. Furthermore, inverse genetic studies based on transcriptomic results have given rise to the discovery of genic alterations in chromosomes 5 and 12 that may help to differentiate tumors with lymph node metastatic potential.

In reference to neural neoplasms, confirmation and validation studies are ongoing, referred to the candidate genes EPHB1, BNIP3 and STAT1, obtained from the genic expression analyses of glioblastomas in patients with an unusually prolonged survival. These identified genes are implicated in signaling pathways and intercellular interactions, in the development and function of the nervous system, and in cell movement and cancer. On the other hand, analyses are being continued of 1p and 19q by FISH in oligodendrogial tumors and their morphological correlation, and of the clinical course and prognostic or predictive value of the methylation status of MGMT in malignant gliomas amenable to treatment with alkylating agents. In 2010, we have introduced the study of a new diagnostic and prognostic marker of malignant gliomas, known as IDH1, the full potential role of which remains to be defined. The research line in head and neck disorders explores the genetic alterations characterizing premalignant lesions of the oral cavity, with special emphasis on those that may be predictive of the development of oral carcinoma. In addition, analyses are made of the molecular alterations implicated in laryngeal cancer, and particularly of acquisition of the metastatic phenotype.

Group of Regulation of Gene Expression in Cell Differentiation and Cancer (Emergent)

POSTIGO, ANTONIO

(IDIBAPS-ICREA)

The laboratory investigates the molecular mechanisms involved in the regulation of gene expression during cell differentiation and in cancer. To that effect, our research focuses on ZEB1 (deltaEF1) and ZEB2 (SIP1) factors, key modulators of cell differentiation, stemness maintenance in normal and cancer stem cells, oncogenic transformation, and tumor invasion and metastasis.

The group uses in vitro and in vivo models to address the following two main research lines:

  1. Study of the mechanisms by which ZEB1 and ZEB2 regulate tumorigenesis and the epithelial-mesenchymal transition (EMT) during cancer progression.
  2. Role of ZEB1 and ZEB2 in the regulation of normal hematopoietic differentiation and its malignant transformation

Research of the group at IDIBAPS has been funded, among other, by grants from the Spanish Ministry of Economy and Competitiveness (formerly, of Science and Innovation), European Union, Spanish Association Against Cancer (AECC), La Caixa Foundation, O. Torres Foundation and AVON Cosmetics SAU.