A5063428489- Adrenal and Paraganglionic Tumors
- Hormonal Regulation and Hypertension
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Pituitary Gland Disorders and Treatments
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Cancer, Lipids, and Metabolism
- Growth Hormone and Insulin-like Growth Factors
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- Immune responses and vaccinations
- Genetic Syndromes and Imprinting
- Genomics and Rare Diseases
- Connective tissue disorders research
- Renal and related cancers
- Thyroid Cancer Diagnosis and Treatment
- 14-3-3 protein interactions
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Neuroblastoma Research and Treatments
- Genetic factors in colorectal cancer
University of Michigan–Ann Arbor
2016-2025
Universidade de São Paulo
2014-2023
Diabetes Australia
2021-2022
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2011-2021
Regional West Medical Center
2015-2020
Hospital de Clínicas
2017
University of North Carolina at Chapel Hill
2017
Instituto do Câncer do Estado de São Paulo
2012-2016
Universidad Unidad
2016
The University of Texas Southwestern Medical Center
2016
Adrenocortical tumors are heterogeneous neoplasms with incompletely understood pathogenesis. IGF-II overexpression has been consistently demonstrated in adult adrenocortical carcinomas.The objective of the study was to analyze expression and its receptor (IGF-IR) pediatric effects a selective IGF-IR kinase inhibitor (NVP-AEW541) on tumor cells.Fifty-seven (37 adenomas 20 carcinomas) from 23 children 34 adults were studied.Gene determined by quantitative real-time PCR. Cell proliferation...
Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic syndromic forms adrenocortical carcinoma (ACC). Abnormal β-catenin staining CTNNB1 mutations are reported to be common both adenoma ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand contribution these tumorigenesis we examined clinicopathological molecular data used mouse models. Evaluation adrenal tumors from 118 adult patients...
Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, usually characterized by functioning macronodules and increased cortisol production. Familial clustering PMAH has been described, suggesting an inherited genetic for this condition. The aim the present study was to identify gene responsible familial PMAH. Forty-seven individuals Brazilian family with were evaluated. A single-nucleotide polymorphism-based genome-wide linkage analysis followed whole-exome...
Context: Adrenarche refers to the rise of dehydroepiandrosterone sulfate (DHEA-S) associated with development a functional adrenal zona reticularis.Clinical features adrenarche include onset body odor, axillary hair, and pubic which reflect increased androgen action.An early in androgens, or premature (PremA), is risk factor for adverse metabolic profiles adolescence adulthood.The bioactive androgens PremA remain poorly understood.The gland potential source testosterone (T) 11-oxygenated...
The transcription factor BCL11B is essential for development of the nervous and immune system, Bcl11b deficiency results in structural brain defects, reduced learning capacity, impaired cell mice. However, precise role humans largely unexplored, except a single patient with missense mutation, affected by multisystem anomalies profound deficiency. Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations BCL11B. Notably, all them are global...
Spatiotemporal control of Wnt signaling is essential for the development and homeostasis many tissues. The transmembrane E3 ubiquitin ligases ZNRF3 (zinc ring finger 3) RNF43 (ring protein 43) antagonize by promoting degradation frizzled receptors. are frequently inactivated in human cancer, but molecular therapeutic implications remain unclear. Here, we demonstrate that adrenocortical-specific loss ZNRF3, not RNF43, results adrenal hyperplasia depends on Porcupine-mediated ligand secretion....
Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. Several genes have been associated with the pathogenesis of CHH, but most cases still remain without molecular diagnosis. The advent next-generation sequencing (NGS) has allowed simultaneous genotyping several regions, faster, making possible extension genetic knowledge CHH.Genetic characterization large cohort Brazilian CHH patients.A 130 unrelated patients (91 males, 39 females) (75 normosmic 55...
Patients born small for gestational age (SGA) who present with persistent short stature could have an underlying genetic etiology that will account prenatal and postnatal growth impairment. We applied a unique massive parallel sequencing approach in cohort of patients exclusively nonsyndromic SGA to simultaneously interrogate clinically substantial variants. To perform investigation children isolated SGA. Screening by exome (n = 16) or targeted gene panel 39) sequencing. Tertiary referral...
Microglia are the tissue-resident macrophages of CNS. They originate in yolk sac, colonize CNS during embryonic development and form a self-sustaining population with limited turnover. A consequence their relative slow turnover is that microglia can serve as long-term memory for inflammatory or neurodegenerative events.Using ATAC-, ChIP- RNA-sequencing, we characterized epigenomes transcriptomes FACS-purified from mice exposed to different stimuli. repeated endotoxin challenge (LPS) was used...
A recent microarray study identified a set of genes whose combined expression patterns were predictive poor outcome in cohort adult adrenocortical tumors (ACTs). The difference between the values measured by qRT-PCR DLGAP5 and PINK1 was best molecular predictor recurrence malignancy. Among carcinomas, BUB1B most reliable overall survival. prognostic heterogeneity ACTs raises need to applicability these markers other cohorts.To validate BUB1B, DLGAP5, as from Brazilian pediatric...
The atrophy and hypofunction of the adrenal cortex following long-term pharmacologic glucocorticoid therapy is a major health problem necessitating chronic replacement that often prolongs ultimate return endogenous adrenocortical function. Underlying this functional recovery anatomic regeneration, cellular molecular mechanisms which are poorly understood. Investigating lineage contribution cortical Sonic hedgehog (Shh)+ progenitor cells SHH-responsive capsular Gli1+ to regenerating cortex,...
Genetic evaluation has been recognized as an important tool to elucidate the causes of growth disorders. To investigate cause short stature and determine phenotype patients with IHH mutations, including response recombinant human hormone (rhGH) therapy. We studied 17 families autosomal-dominant by using whole exome sequencing screened defects in 290 Molecular analyses were performed evaluate potential impact N-terminal variants. identified 10 pathogenic or possibly variants IHH, regulator...
Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with few therapies; however, patients locoregional disease have variable outcomes. The Cancer Genome Atlas project on ACC (ACC-TCGA) identified that cancers of homogeneously rapidly recurrent or fatal bear unique CpG island hypermethylation phenotype, "CIMP-high." We sought to identify biomarker faithfully captures this subgroup.Experimental Design: analyzed ACC-TCGA data characterize differentially regulated biological...
Abstract Context Massively parallel sequencing (MPS) technologies have emerged as a first-tier approach for diagnosing several pediatric genetic syndromes. However, MPS has not been systematically integrated into the diagnostic workflow along with clinical/biochemical data 46,XY differences of sex development (DSD). Objective To analyze contribution phenotypic classification either alone or in association evaluations, mainly MPS, large cohort DSD patients. Design/patients 209 nonsyndromic...
Steroidogenic factor 1 (SF-1) is a key determinant of endocrine development and function adrenal cortex. SF-1 overexpression gene amplification were previously demonstrated in small group pediatric adrenocortical tumors.Our objective was to determine the frequency protein expression large cohort adult tumors.SF-1 assessed 103 tumors from 36 children 67 adults, whereas studied 38 (17 children).Tissue microarray, multiplex ligation-dependent probe amplification, quantitative real-time PCR...