Group Leader Eduardo Arzt NEUROENDOCRINOLOGY and IMMUNOLOGY Molecular and functional neuro-immune pathways The aim of our group is to understand of how hormone and cytokine signals are integrated in the framework of normal and pathological neuroendocrine and immune circuits at the level of cellular signaling, new target genes and cross-talk of transcription factors. We employ animal and cellular models, and collaborate in studies in patient pathology, in our research. Novel signaling pathways of corticotropin releasing hormone (CRH): Our previous results indicate that CRH stimulation of pituitary corticotrops activates the Mitogen-Activated protein kinase (MAPK) pathway. In order to contribute to the understanding of the signaling pathways of CRH in the central nervous system (CNS) we study specific kinase pathways activated in neurons. We are searching by means of confocal microscopy and antibodies specific for phosphorylated forms of activated MAPK in the CNS of mice (normal animals and several strains genetically modified in the CRH pathway -CRH-R1 and R2 KO, CRH-R1 conditional KO), injected icv with CRH. We are characterizing the molecular details of the MAPK pathways defined in vivo by the CRH icv studies, by further studies in cellular models (i.e. HT22 and HN9 cells). The answers to these questions could open new avenues in the pharmacological treatment of the CRH system. Efforts aim to identify and describe molecular transcriptional pathways involved in pituitary tumor pathogenesis. We use a specific directed approach in which specific factors are analyzed (smads for BMP-4/TGF-Beta -family and STAT cascades for gp130 cytokines) and an open/unbiased study of gene differential expression by means of microarray analysis. The functional relevance of the induced factors in tumor formation is studied in nude mice (an animal model for tumorigenesis) in which we inject the pituitary tumoral cell clones obtained by stable transfection either with the active or inactive forms of the transcription factors. This project contributes to the understanding of brain pituitary tumor pathogenesis, and its potential molecular pharmacological treatment. Specific functions in endocrine epithelial cells need to be controlled by integrated mechanisms that allow the coordination of endocrine signals together with paracrine and autocrine signals within the glands but little is known about the integration of these pathways at the molecular level. We study the mechanisms involved in the integration and regulatory interaction (cross-talk) of specific cytokine and hormone signals that regulate cell function, at the transcriptional level that controls gene expression and determines the action of estrogens and glucocorticoid hormones on their target tissues. Hormones, neuropeptides and cytokines interact at different levels maintaining the homeostasis of the whole body. Several pathological conditions show an imbalance between molecular messengers of the endocrine, nervous and immune systems. We focus on the molecular manipulation of key immune cells (eg., T and dendritic cells) by means of gene transfer and pharmacological conditioning with the final goal to be employed as therapeutic tools in immune disorders. Associated researchers Marta Labeur (Junior researcher at Max-Planck Insitute, Munich) Marcelo Perone Susana Silberstein Research group Matias Acuña Alberto Carbia Nagashima Jimena Druker Damiana Paula Giacomini Juan Gerez Ana Liberman Damián Refojo (until March 2006) Jose Bonfiglio Mariana Graciarena (until December 2003) Sebastian Sosa Damian Bellio (technician until May 2007) Carlos Gregorio Echenique (until December 2003)