Translational Molecular Pathology

Our group aims to unravel the molecular mechanisms of cancer progression and metastasis to identify new diagnostic, prognostic and therapeutic targets in cancer. By combining the knowledge and availability of human tumors in the Pathology department with the expertise of the basic molecular cell biology research group, we focus on:

Understanding: the molecular mechanisms underlying clonal cooperation and intercellular communication in heterogeneous tumors.
The role of MNK kinases in cellular stress resistance.
The role of ITGB3 in intercellular communication via extracellular vesicles in cancer metastasis (Santiago Ramon y Cajal).
The role of direct cell-cell communication via gap junctions and intercellular protrusions in cancer (Trond Aasen)
The malignant transition of Plexiform Neurofibromas (Cleofe Romagosa).

Research lines

Genomic transcriptional profile analysis in proliferative inflammatory atrophy (PIA) as a possible precursor of human prostate cancer

To analyse transcriptional profiles of normal, PIA (proliferative inflammatory atrophy), PIN (prostatic intraepithelial neoplasia) and tumoral prostate using microarrays of selected tumoral tissue of prostatectomy specimens, in order to characterize gene expression modifications in prostate cancer versus PIN and PIA.

To analyse the biological response on tumoral / non-tumoral and co-culture them with monocytes in order to study transcriptional profile changes.

From all the data obtained, overexpressed / underexpressed genes are being identified and validated. Stromal and inflammatory genes also will be explored for their potential use as early markers for prostatic cancer and their ability to identify PIA as a precursor lesion.

(Prostate Research Traslational Unit.)

IP: Inés de Torres Ramirez

Identification of molecular targets associated with tumor progression and therapy resistance in colorectal carcinoma.

Studying in colorectal cancer mechanisms of action of the central signal transduction pathways, identify potential molecular alterations that can be used as therapeutic targets and characterize the degree of genetic inestability.

IP: Santiago Ramon y Cajal Agüeras

Involvement of the human Hepatitis A Viral Receptor (hHAVcr-1) in renal cancer development and progression. Value as a diagnostic and prognostic biomarker in renal carcinomas

We have postulated that hHAVcr-1 might constitute an important biomarker for early detection of ccRCC and could also be used as a target for therapy of kidney carcinomas, since immunotoxins directed against the monkey homologue of hHAVcr-1 could kill kidney cells.

Specific aims are focused to: i) determine the diagnostic and prognostic potential of hHAVcr-1 expression in renal cell carcinomas, by correlating hHAVcr-1 levels in archive, fresh surgical and TMA tissues with tumor anatomo-pathological characteristics and patients outcome and, ii) determine the function of hHAVcr-1, which remains elusive, in development and progression of kidney carcinomas, using ccRCC derived cell lines with silenced or overexpressed hHAVcr-1. Tumors overexpressing or defective in hHAVcr-1 will be compared with controls, in relation to their behavior and anatomo-pathological characteristics. Differences are being correlated with proteomic and gene expression profiles obtained on each case. Differential expression pathways and target molecules correlating with absence/presence of hHAVcr-1 shall be identified. New strategies for diagnosis, prognosis and treatment of ccRCC must be further developed.

(Programa de Recerca en Cancer Renal CIBBIM-IRHUVH. )

IP: Inés de Torres Ramirez

Long-term mast cell stabilization downregulates mucosal microinflammation in the jejunum of diarrhea-prone irritable bowel syndrome (IBS)

Study of the effect of mast-cell stabilization on mucosal inflammation and the clinical response. Inmunohistochemistry analysis of microinflammation (mast cells, intraepithelial lymphocytes and eosinophils) in Irritable Bowel Syndome (IBS) Biological inflammation was evaluated in pooled biopsies by quantitative real time PCR to analyze the expression of preselected genes implicated in innate inmunity (Toll-like receptors (TLR) and defensins (DEF)), mast cell activation and growth and neuronal regulation.. Mucosal eosinophils show restrained activation in the yeyunum od diarrhea –prone irritable bowel sindrome patiens

Pharmacological stabilization of mucosal mast cells effectively reduces pro-inflammatory gene expression profiles in the jejunal mucosa of D-IBS patients and concomitantly improves clinical manifestations.

( Digestive Disease Research Unit)

IP: Inés de Torres Ramirez