Patologia Molecular Translacional

Nuestro grupo pretende elucidar los mecanismos moleculares implicados en la progresión tumoral hasta sus metástasis con el fin de identificar nuevos marcadores diagnósticos, pronósticos así como nuevas dianas terapéuticas. Gracias al profundo conocimiento en las bases moleculares tumorales del grupo de investigación, así como la disponibilidad de muestras tumorales humanas, desarrollamos diferentes líneas de investigación centradas en:

Conocer los mecanismos moleculares que subyacen de la cooperación clonal así como la comunicación intercelular implicadas en la heterogeneidad tumoral.
Describir el papel de las MNKs en el desarrollo de resistencias frente al estrés celular.
Ahondar en el papel de ITGB3 en la comunicación intercelular mediada por vesículas extracelulares en modelos de metástasis (Santiago Ramón y Cajal).
Estudiar de las comunicaciones célula-célula mediante uniones intercelulares comunicantes (gap junctions) y/o protrusiones celulares en cáncer (Trond Aasen).
Estudiar de la transformación oncogénica de los Neurofibromas plexiformes (Cleofe Romagosa).

Líneas de investigación

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