A5074322188- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Erythrocyte Function and Pathophysiology
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Blood properties and coagulation
- NF-κB Signaling Pathways
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Hemoglobinopathies and Related Disorders
- interferon and immune responses
- Pancreatic function and diabetes
- Cancer-related Molecular Pathways
- MicroRNA in disease regulation
- Cancer-related gene regulation
- FOXO transcription factor regulation
- Cancer Genomics and Diagnostics
- Blood groups and transfusion
- Acute Myeloid Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Complement system in diseases
- Colorectal Cancer Treatments and Studies
Universidade de São Paulo
2014-2024
Universidade Cidade de São Paulo
2022
Harvard University
2010-2016
Beth Israel Deaconess Medical Center
2005-2016
Harvard Stem Cell Institute
2016
UNC Lineberger Comprehensive Cancer Center
2006-2014
University of North Carolina at Chapel Hill
2006-2014
Hadassah Medical Center
2004-2006
Universidade Estadual de Campinas (UNICAMP)
1994-2005
Hospital de Clínicas da Unicamp
2005
Mutations constitutively activating FLT3 kinase are detected in approximately 30% of acute myelogenous leukemia (AML) patients and affect downstream pathways such as extracellular signal-regulated (ERK)1/2. We found that activation human AML inhibits CCAAT/enhancer binding protein alpha (C/EBPalpha) function by ERK1/2-mediated phosphorylation, which may explain the differentiation block leukemic blasts. In MV4;11 cells, pharmacological inhibition either or MEK1 leads to granulocytic...
K-Ras-induced lung cancer is a very common disease, for which there are currently no effective therapies. Because therapy directly targeting the activity of oncogenic Ras has been unsuccessful, different approach novel design to identify critical downstream targets. Given that proteins activate transcription factor NF-kappaB, and importance NF-kappaB in oncogenesis, we hypothesized would be an important K-Ras target cancer. To address this hypothesis, generated NF-kappaB-EGFP reporter mouse...
The serine/threonine protein kinase Akt promotes cell survival, growth, and proliferation through phosphorylation of different downstream substrates. A key effector is the mammalian target rapamycin (mTOR). known to stimulate mTORC1 activity tuberous sclerosis complex 2 (TSC2) PRAS40, both negative regulators mTOR activity. We previously reported that IκB α (IKKα), a component leads NF-κB activation, plays an important role in promoting activated Akt. Here, we demonstrate IKKα-dependent...
Abstract Background Activating mutations in KRAS are prevalent lung cancer and have been causally linked to the oncogenic process. However, therapies targeted RAS ineffective date identification of targets that impinge on phenotype is warranted. Based published studies showing mitotic kinases Aurora A (AURKA) B (AURKB) cooperate with promote malignant transformation AURKA phosphorylates effector pathway components, aim this study was investigate whether AURKB targeting these might be...
In lung cancers with low expression of C/EBPα, BMI1 correlates worse prognosis but can be targeted a drug.
Abstract We showed previously that CCAAT/enhancer binding protein α (C/EBPα), a tissue-specific transcription factor, is candidate tumor suppressor in lung cancer. In the present study, we have performed transcriptional profiling study of C/EBPα target genes using an inducible cell line system. This led to identification hepatocyte nuclear factor 3β (HNF3β), known play role airway differentiation, as downstream C/EBPα. found down-regulation HNF3β expression large proportion cancer lines...
The leucine zipper family transcription factor CCAAT enhancer binding protein alpha (C/EBP␣) inhibits proliferation and promotes differentiation in various cell types.In this study, we show, using a lung-specific conditional mouse model of C/EBP␣ deletion, that loss the respiratory epithelium leads to failure at birth due an arrest type II alveolar program.This results lack I cells differentiated surfactant-secreting cells.In addition showing block differentiation, neonatal lungs display...
Activating mutations in KRAS are prevalent cancer, but therapies targeted to oncogenic RAS have been ineffective date. These results argue that targeting downstream effectors of will be an alternative route for blocking RAS-driven pathways. We and others shown activates the NF-κB transcription factor pathway KRAS-induced lung tumorigenesis is suppressed by expression a degradation-resistant form IκBα inhibitor or genetic deletion IKKβ RELA/p65 subunit NF-κB. Here, pharmacological approaches...
Abstract Lung cancer is the leading cause of deaths. Tumor heterogeneity, which hampers development targeted therapies, was herein deconvoluted via single cell RNA sequencing in aggressive human adenocarcinomas (carrying Kras -mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation conserved both lung cancer. previously reported key role for oncogene BMI-1 adenocarcinomas. therefore investigated effects vivo PTC596 treatment, affects...
Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In several kindreds with recessive, ankyrin-deficient HS, mutations have been identified in ankyrin promoter that proposed to decrease synthesis. We analyzed effects two mutations, −108T C and cis −153G A, on expression. No difference between wild type mutant promoters was demonstrated transfection or gel shift assays vitro. Transgenic mice a linked humanAγ-globin gene expressed γ-globin 100% erythrocytes copy...
Abstract Lung cancer is the leading cause of deaths. Lethal pulmonary adenocarcinomas (ADC) present with frequent mutations in EGFR. Genetically engineered murine models lung expedited comprehension molecular mechanisms driving tumorigenesis and drug response. Here, we systematically analyzed evolution tumor heterogeneity context dynamic interactions occurring intermingled microenvironment (TME) by high-resolution transcriptomics. Our effort identified vulnerable tumor-specific epithelial...
Hereditary spherocytosis (HS) is a common hemolytic anemia caused by defects in the erythrocyte membrane proteins. The screening of mutations ankyrin-1 (ANK1) gene 28 Brazilian HS patients showed two new missense (His276Arg and Ile1054Thr) one novel promoter mutation (-153 G-->A). His276Arg affected invariable TPLH sequence on repeat 9. -153 was linked cis to known -108 T-->C mutation. In contrast other populations, we were able detect only 10% our patients. It also interesting point out...
Peptide active ingredients show great promise regarding the treatment of various health-endangering diseases. It is reported that L-lysine inhibits proliferation several tumour lines in vitro and vivo. However, proteins peptide drugs possess certain disadvantages such as vivo instability short biological half-life. On grounds drug delivery systems can overcome a wide spectrum bioactive compounds issues, biopolymeric blend-based microparticulated system capable delivering ε-polylysine (PLL)...