“Hepatitis A viral receptor (HAVR) / kidney injury molecule-1 (kim-1): Cancer and renal regeneration implications–HAVR/KIM-1 in renal tubular damage/regeneration “
Principal investigators: Anna Meseguer Navarro and Marta Riera Oliva 
In this project we try to elucidate the role of KIM-1 in ischemia-reperfusion or nephrotoxic-induced renal tubular lesion. This protein is overexpressed of in acute tubular lesion but it is yet unclear why. It may be involved either in tubular epithelium regeneration or have a role enhancing the damage. Using tubular cell culture models we will study whether the changes in KIM-1 expression have a correlation with the regeneration of the renal proximal tubule and therefore If It could have eventual therapeutic applications.
“Hepatitis A viral receptor (HAVR) / kidney injury molecule-1 (kim-1): Cancer and renal regeneration implications. HAVR/KIM-1 role in development and progression in human clear cells renal carcinoma (ccRCC) “
Principal investigators: Anna Meseguer Navarro and Maria Rosa Vilá
We have described HAVR/KIM-1 overexpression in 60% ccRCC. Its overexpression in ccRCC cell lines blocks cellular differentiation and induces cellular tight junction lost. We want to determine HAVR/KIM-1 diagnostic and prognostic value in human ccRCC evolution and to study HAVR/KIM-1 participation in tumoral progression by modifying its expression (overexpression versus silencing) in certain ccRCC cell lines known to be able to induce tumors in immunodepresed mice.
“Androgen action on renal physiopathology. Cyclophylin (Cyp) and acute renal failure. Mechanisms and biomarkers in cyclosporine induced renal toxicity”
Principal investigators: Anna Mesguer Navarro and Joan Lopez Hellin
Cyps are proteins of unknown endogenous function but with a well established peptidyl-prolyl cis-trans isomerase (PPIasa) activity which is inhibited by CsA. Folding and repair functions and a role as a chaperon are other activities attributed to these proteins. We hypothesize that CsA proximal tubule induced toxicity may be related to PPIasa activity inhibition. Our goal is to identify targets of this activity in these cells. We will determine proteomic changes produced after the inhibition of the PPIases specific for CypA,B and D by using RNAi or dominant negative techniques for each of them. We expect to see decreased or increased levels of proteins that could represent future targets in the prevention of CsA induced toxicity.
“Androgen action in renal physiopathology. KAP protein functional analysis”
Principal investigator: Anna Meseguer Navarro
KAP mRNA and protein levels are modified by renal ischemia or CsA related toxicity. In this later case KAP degradation has been observed, whereas KAP overexpression protects from CsA induced toxicity in cellular models. KAP interacts with CsA receptor, CypB. Since KAP constitutes a calpain target, we postulate a protective role of KAP acting on the proximal tubule in the processes, such as CsA induced toxicity, where this protease is active. We have generated KAP transgenic animals and in the process of obtaining conditional knock-outs to study KAP role in renal physiopathology, paying attention to histopathological changes, renal function and transcriptome, both in steady state and damage situations.
“Androgen action on renal physiopathology. Mechanisms of transcriptional regulation of proximal tubule specific genes”
Principal investigators: Anna Mesguer Navarro
Among the proximal tubule specific genes controlled by androgens identified in our lab, we are working specially on the kidney androgen-regulated protein (KAP) coding gene. We are characterizing the functional elements that control its expression in renal proximal tubule epithelial cells in response to androgens using a 1500bp proximal promoter fragment capable to direct heterologous gene expression in the proximal tubule of several transgenic models.
“Focal segmental Glomeruloseclerosis“
Principal investigator: Joan López Hellin
Non-familial idiopathic focal segmental glomerulosclerosis (FSGE) very often leads to terminal renal disease and currently lacks of an effective treatment. Our goal is, by using differential proteomic analysis, to detect and identify a putative blood factor that may be causing the proteinuria in these patients. Hopefully this Information can help to discover the cause of the disease. We are performing these studies using serum from pediatric patients.
“Molecular mechanisms involved in mitochondrial DNA depletion induced by thymidine kinase 2 (TK2) gene mutations“
Principal investigator: Maya Vila Iglesias
Mitocondrial DNA depletion syndrome (MDS) is characterized by mtDNA copy number decrease. TK2 and dGK gene mutations account for approximately 20% MDS cases. In this project we study from a molecular point of view how TK2 mutations lead to the MDS. We will analyze the effect of this gene alteration on: 1/ expression and/or regulation of other genes involved in mtDNA transcription and replication; 2/ in the nucleotide balance between the cytoplasmic and mitochondrial pools.