A5028308930- Protein Kinase Regulation and GTPase Signaling
- Phosphodiesterase function and regulation
- Renal and related cancers
- Congenital heart defects research
- Genetics, Aging, and Longevity in Model Organisms
- Congenital Ear and Nasal Anomalies
- Estrogen and related hormone effects
- Tracheal and airway disorders
- RNA Research and Splicing
- MicroRNA in disease regulation
- Renal cell carcinoma treatment
- Retinoids in leukemia and cellular processes
- Stress Responses and Cortisol
- Macrophage Migration Inhibitory Factor
- PI3K/AKT/mTOR signaling in cancer
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Mass Spectrometry Techniques and Applications
- Signaling Pathways in Disease
- Genetic and Kidney Cyst Diseases
- Genomics and Chromatin Dynamics
- Receptor Mechanisms and Signaling
- Nuclear Receptors and Signaling
- Birth, Development, and Health
Universidad Maimónides
2023
Consejo Nacional de Investigaciones Científicas y Técnicas
2003-2023
University of Buenos Aires
2002-2022
Fundación Ciencias Exactas y Naturales
2002-2022
Magee-Womens Research Institute
2015-2016
UPMC Hillman Cancer Center
2015-2016
Cancer Research Center
2015-2016
University of Pittsburgh
2007-2011
Max Planck Institute of Psychiatry
2002
Max Planck Society
2002
Abstract Nur factors are critical for proopiomelanocortin (POMC) induction by CRH in corticotrophs, but the pathways linking to unknown. In this study we show that AtT-20 corticotrophs and cAMP induce Nur77 Nurr1 expression transcription at NurRE site protein kinase A (PKA) calcium-dependent -independent mechanisms. Calcium depend on calmodulin II (CAMKII) activity, calcium-independent accounted part MAPK activation (Rap1/B-Raf/MAPK-ERK kinase/ERK1/2), demonstrated use of molecular...
Exposure to sources of UV radiation, such as sunlight, induces a number cellular alterations that are highly dependent on its ability affect gene expression. Among them, the rapid activation genes coding for two subfamilies proto-oncoproteins, Fos and Jun, which constitute AP-1 transcription factor, plays key role in subsequent regulation expression involved DNA repair, cell proliferation, cycle arrest, death by apoptosis, tissue extracellular matrix remodeling proteases. Besides being...
Thyroid cancer is the most common type of endocrine malignancy, encompassing tumors with various levels invasive growth and aggressiveness. Rap1GAP, a Rap1 GTPase-activating protein, inhibits RAS superfamily protein by facilitating hydrolysis GTP to GDP. In this study, we analyzed 197 thyroid tumor samples showed that Rap1GAP was frequently lost or downregulated in types tumors, particularly aggressive forms cancer. The downregulation due promoter hypermethylation and/or loss heterozygosity,...
The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that hormones, cortisol, catecholamines induce rapid DNA damage repair in NIH 3T3 fibroblasts. This study investigates whether increase cells if this impacts drug efficacy.We first screened a panel of 39 cell lines for expression adrenergic glucocorticoid receptors examined alter cycle regulation vitro. A TNBC xenograft model was used to assess the...
cAMP stimulates proliferation in many cell types. For years, cAMP-dependent protein kinase (PKA) represented the only known effector. PKA, however, does not fully mimic action of cAMP, indicating existence a PKA-independent component. Since cAMP-mediated activation G-protein Rap1 and its phosphorylation by PKA are strictly required for effects on mitogenesis, we hypothesized that activator Epac might represent factor. Here report acts synergistically with mitogenesis. We have generated new...
The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development unfavorable conditions, and modulation of adult aging. Despite biologic importance DAF-12, target genes for this are largely unknown. To identify targets, we performed chromatin immunoprecipitation followed by hybridization whole-genome tiling arrays. We identified 1,175 genomic regions be bound vivo these enriched known binding motifs act as response elements transfected cells transgenic...
Guanine nucleotide exchange factors (GEFs) and their associated GTP-binding proteins (G-proteins) are key regulatory elements in the signal transduction machinery that relays information from extracellular environment into specific intracellular responses. Among them, MAPK cascades represent ubiquitous downstream effector pathways. We have previously described that, analogous to Ras-dependent activation of Erk-1/2 pathway, members Rho family small G-proteins activate JNK cascade when GTP is...
Rap1b has been implicated in the transduction of cAMP mitogenic response. Agonists that increase intracellular rapidly activate (i.e. GTP binding) and phosphorylate on Ser(179) at its C terminus. cAMP-dependent protein kinase (PKA)-mediated phosphorylation is required for mitogenesis, tumorigenesis, inhibition AKT activity. However, role still remains unknown. In this study, we utilized amide hydrogen/deuterium exchange mass spectroscopy (DXMS) to assess potential conformational changes...
cAMP is an ubiquitous second messenger. Localized areas with high concentration, i.e. microdomains, provide elegant mechanism to generate signaling specificity and transduction efficiency. However, the mechanisms underlying effector targeting into these compartments still unclear. Here we report identification of radixin as a scaffolding unit for both effectors, Epac PKA. This complex localizes in submembrane compartment where synthesis occurs. Compartment disruption by shRNA dominant...
The number of laboratories using the free living nematode C. elegans is rapidly growing. popularity this biological model attributed to a rapid generation time and short life span, easy inexpensive maintenance, fully sequenced genome, array RNAi resources mutant animals. Additionally, analysis genome revealed great similarity between worms higher vertebrates, which suggests that research in could be an important adjunct studies performed whole mice or cultured cells. A powerful part worm...
CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding protein-7 (CHD7) and characterized retarded growth malformations heart nervous system. Despite public health relevance of this disorder, relevant cellular pathways targets CHD7 that relate to disease pathology are still poorly understood. Here we report chd-7, nematode ortholog Chd7, required for dauer morphogenesis, lifespan determination, stress response, body size...
The molecular events driving specification of the kidney have been well characterized. However, how initial field size is established, patterned, and proportioned not Lhx1 a transcription factor expressed in pronephric progenitors required for kidney, but few interacting proteins or downstream targets identified. By tandem-affinity purification, we isolated FRY like transcriptional coactivator (Fryl), one two paralogous genes, fryl furry (fry), described vertebrates. Both were found to...
Abstract The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given high evolutionary conservation gene expression segmentation patterning between mammalian amphibian nephrons, Xenopus laevis pronephric kidney offers a simplified model for studying nephrogenesis. Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes by forming multiprotein complexes with LIM binding protein 1...
ABSTRACT CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding protein7 (CHD7) and characterized retarded growth malformations heart nervous system. Despite public health relevance of this disorder, relevant targets CHD7 that relate to disease pathology are still poorly understood. Here we report chd-7 , nematode ortholog Chd7, required for dauer morphogenesis, lifespan determination, stress response. Consistent with our discoveries,...
The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given high evolutionary conservation gene expression segmentation patterning between mammalian amphibian nephrons, Xenopus laevis pronephric kidney offers a simplified model for studying nephrogenesis. Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes by forming multiprotein complexes with LIM binding protein 1 (Ldb1)....