Jorge Andrade - Academia.edu (original) (raw)

Papers by Jorge Andrade

International Journal of Molecular Sciences

Night shift work increases risk of metabolic disorders, particularly obesity and insulin resistan... more Night shift work increases risk of metabolic disorders, particularly obesity and insulin resistance. While the underlying mechanisms are unknown, evidence points to misalignment of peripheral oscillators causing metabolic disturbances. A pathway conveying such misalignment may involve exosome-based intercellular communication. Fourteen volunteers were assigned to a simulated day shift (DS) or night shift (NS) condition. After 3 days on the simulated shift schedule, blood samples were collected during a 24-h constant routine protocol. Exosomes were isolated from the plasma samples from each of the blood draws. Exosomes were added to naïve differentiated adipocytes, and insulin-induced pAkt/Akt expression changes were assessed. ChIP-Seq analyses for BMAL1 protein, mRNA microarrays and exosomal miRNA arrays combined with bioinformatics and functional effects of agomirs and antagomirs targeting miRNAs in NS and DS exosomal cargo were examined. Human adipocytes treated with exosomes from...

Endothelial Cells Don’t Waste: Endothelial-Derived Lactate Boosts Muscle Regeneration

Developmental Cell

Pathogenesis of Human Papillomaviruses Requires the ATR/p62 Autophagy-Related Pathway

mBio

High-risk human papillomaviruses (HPVs) constitutively activate the ataxia telangiectasia and Rad... more High-risk human papillomaviruses (HPVs) constitutively activate the ataxia telangiectasia and Rad3-related (ATR) DNA damage response pathway, and this is required for viral replication. In fibroblasts, activated ATR regulates transcription of inflammatory genes through its negative effects on the autophagosome cargo protein p62. In addition, suppression of p62 results in increased levels of the transcription factor GATA4, leading to cellular senescence. In contrast, in HPV-positive keratinocytes, we observed that activation of ATR resulted in increased levels of phosphorylated p62, which in turn lead to reduced levels of GATA4. Knockdown of ATR in HPV-positive cells resulted in decreased p62 phosphorylation and increased GATA4 levels. Transcriptome sequencing (RNA-seq) analysis of HPV-positive cells identified inflammatory genes and interferon factors as negative transcriptional targets of ATR. Furthermore, knockdown of p62 or overexpression of GATA4 in HPV-positive cells leads to i...

Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism

Nature

System for Informatics in the Molecular Pathology Laboratory (SIMPL): An Open-Source End-to-End Solution for Next-Generation Sequencing Clinical Data Management

The Journal of molecular diagnostics : JMD, Jan 23, 2018

Next-generation sequencing (NGS) diagnostic assays are increasingly becoming the standard of care... more Next-generation sequencing (NGS) diagnostic assays are increasingly becoming the standard of care in oncology practice. As the scale of an NGS laboratory grows, management of these assays requires organizing large amounts of information, including patient data, laboratory processes, genomic data, as well as variant interpretation and reporting. Although several Laboratory Information Systems (LIS) and/or Laboratory Information Management Systems (LIMS) are commercially available, they may not meet all of the needs of a given laboratory, in addition to being frequently cost prohibitive. Herein, we present System for Informatics in the Molecular Pathology Laboratory (SIMPL), a free and open-source LIS/LIMS system for academic and nonprofit molecular pathology NGS laboratories, developed at the Genomic and Molecular Pathology division at the University of Chicago Medicine (UCM-GMP). SIMPL was designed as a modular end-to-end information system to handle all stages of the NGS laboratory...

Clinical cancer research : an official journal of the American Association for Cancer Research, 2018

Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical functi... more Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS-HOX interactions in prostate cancer etiology and progression. The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored. Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression. These analyses demonstrate a stepwise decrease in the expression of both MEIS1 and MEIS2 from benign epithelia, to primary tumor, to metastatic tissues. Positive expression of MEIS proteins in primary tumors, however, is associated with a lower hazard of clinical metastasis (HR = 0.28) after multivariable analysis. Pathway and gene set enrichment analyses identified MEIS-associated networks involved in cMYC signaling, cellular proliferation, motility, and local tumor environment. Depleti...

Nature communications, May 4, 2018

The oligometastasis hypothesis suggests a spectrum of metastatic virulence where some metastases ... more The oligometastasis hypothesis suggests a spectrum of metastatic virulence where some metastases are limited in extent and curable with focal therapies. A subset of patients with metastatic colorectal cancer achieves prolonged survival after resection of liver metastases consistent with oligometastasis. Here we define three robust subtypes of de novo colorectal liver metastasis through integrative molecular analysis. Patients with metastases exhibiting MSI-independent immune activation experience the most favorable survival. Subtypes with adverse outcomes demonstrate VEGFA amplification in concert with (i) stromal, mesenchymal, and angiogenic signatures, or (ii) exclusive NOTCH1 and PIK3C2B mutations with E2F/MYC activation. Molecular subtypes complement clinical risk stratification to distinguish low-risk, intermediate-risk, and high-risk patients with 10-year overall survivals of 94%, 45%, and 19%, respectively. Our findings provide a framework for integrated classification and tr...

Memorias do Instituto Oswaldo Cruz, 2018

Acute Chagas disease (ACD) has a distinct epidemiological profile in the Amazon Region, with case... more Acute Chagas disease (ACD) has a distinct epidemiological profile in the Amazon Region, with cases and outbreaks of Trypanosoma cruzi infection being possibly related to the ingestion of contaminated food. Data on ACD in the state of Pará retrieved from 2000 to 2016 from the Brazilian Notifiable Diseases Information System (SINAN) were evaluated. During this period, 2,030 of the 16,807 reported cases were confirmed, with a higher incidence between the months of August and December, thus characterising a seasonal pattern of acute infection, and coinciding with the higher production of "açaí", one fruit likely involved in the oral transmission of the disease. Evaluation of the absolute numbers of confirmed ACD cases secondary to oral infection suggests that infection through this route increased during the 2010-2016 period, differing from what was recorded in terms of vectorial or other infection routes. These findings point to the need of intensifying strategies to prevent ...

Cell reports, Jan 10, 2018

The emergence of influenza A viruses (IAVs) from zoonotic reservoirs poses a great threat to huma... more The emergence of influenza A viruses (IAVs) from zoonotic reservoirs poses a great threat to human health. As seasonal vaccines are ineffective against zoonotic strains, and newly transmitted viruses can quickly acquire drug resistance, there remains a need for host-directed therapeutics against IAVs. Here, we performed a genome-scale CRISPR/Cas9 knockout screen in human lung epithelial cells with a human isolate of an avian H5N1 strain. Several genes involved in sialic acid biosynthesis and related glycosylation pathways were highly enriched post-H5N1 selection, including SLC35A1, a sialic acid transporter essential for IAV receptor expression and thus viral entry. Importantly, we have identified capicua (CIC) as a negative regulator of cell-intrinsic immunity, as loss of CIC resulted in heightened antiviral responses and restricted replication of multiple viruses. Therefore, our study demonstrates that the CRISPR/Cas9 system can be utilized for the discovery of host factors critic...

New Q(ues) to keep blood vessels growing

The EMBO journal, Aug 15, 2017

Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations

Translational stroke research, Feb 17, 2017

The clinical course of cerebral cavernous malformations (CCMs) is highly variable. Based on recen... more The clinical course of cerebral cavernous malformations (CCMs) is highly variable. Based on recent discoveries implicating angiogenic and inflammatory mechanisms, we hypothesized that serum biomarkers might reflect chronic or acute disease activity. This single-site prospective observational cohort study included 85 CCM patients, in whom 24 a priori chosen plasma biomarkers were quantified and analyzed in relation to established clinical and imaging parameters of disease categorization and severity. We subsequently validated the positive correlations in longitudinal follow-up of 49 subjects. Plasma levels of matrix metalloproteinase-2 and intercellular adhesion molecule 1 were significantly higher (P = 0.02 and P = 0.04, respectively, FDR corrected), and matrix metalloproteinase-9 was lower (P = 0.04, FDR corrected) in patients with seizure activity at any time in the past. Vascular endothelial growth factor and endoglin (both P = 0.04, FDR corrected) plasma levels were lower in pat...

The Journal of physiology, Apr 15, 2017

Late gestation during pregnancy has been associated with a relatively high prevalence of obstruct... more Late gestation during pregnancy has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia, a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis and metabolic function in offspring. Here we show that late gestation intermittent hypoxia induces metabolic dysfunction as reflected by increased body weight and adiposity index in adult male offspring that is paralleled by epigenomic alterations and inflammation in visceral white adipose tissue. Fetal perturbations by OSA during pregnancy impose long-term detrimental effects manifesting as metabolic dysfunction in adult male offspring. Pregnancy, particularly late gestation (LG), has been associated with a relatively high prevalence of obstructive sleep apnoea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis, and metabolic function in offspring. We hypothesiz...

Scientific reports, Feb 27, 2017

Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic interm... more Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, increased accumulation and proliferation of pro-inflammatory metabolic M1-like macrophages highly expressing CD36, emerged in aorta. Transcriptomic and MeDIP-seq approaches identified activation of pro-atherogenic pathways involving a complex interplay of histone modifications in functionally-relevant biological pathways, such as inflammation and oxidative stress in aorta macrophages. Discontinuation of CIH did not elicit significant improvements in aorta wall macrophage phenotype. However, CIH-induced aorta changes were absent in CD36 knockout mice, Our results provide mechanistic insights showing that CIH exposures during sleep in absence of concurrent pro-atherogenic settings (i.e., genetic propensity or dietary manipulation) lead to the re...

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 24, 2017

Molecular-based cancer tests have been developed to augment the standard clinical and pathologic ... more Molecular-based cancer tests have been developed to augment the standard clinical and pathologic features used to tailor treatments to individual breast cancer patients. Homologous recombination (HR) repairs double-stranded DNA breaks and promotes tolerance to lesions that disrupt DNA replication. Recombination Proficiency Score (RPS) quantifies HR efficiency based on the expression of four genes involved in DNA damage repair. We hypothesized low RPS values can identify HR-deficient breast cancers most sensitive to DNA-damaging chemotherapy. We collected pathologic tumor responses and tumor gene expression values for breast cancer patients that were prospectively enrolled on clinical trials involving pre-operative chemotherapy followed by surgery (N=513). We developed an algorithm to calculate breast cancer-specific RPS (RPSb) values on an individual sample basis. Low RPSb tumors are approximately twice as likely to exhibit a complete pathologic response or minimal residual disease ...

Proceedings of the National Academy of Sciences, 2016

Antigen processing and presentation genes found within the MHC are among the most highly polymorp... more Antigen processing and presentation genes found within the MHC are among the most highly polymorphic genes of vertebrate genomes, providing populations with diverse immune responses to a wide array of pathogens. Here, we describe transcriptome, exome, and whole-genome sequencing of clonal zebrafish, uncovering the most extensive diversity within the antigen processing and presentation genes of any species yet examined. Our CG2 clonal zebrafish assembly provides genomic context within a remarkably divergent haplotype of the core MHC region on chromosome 19 for six expressed genes not found in the zebrafish reference genome: mhc1uga, proteasome-β 9b (psmb9b), psmb8f, and previously unknown genes psmb13b, tap2d, and tap2e. We identify ancient lineages for Psmb13 within a proteasome branch previously thought to be monomorphic and provide evidence of substantial lineage diversity within each of three major trifurcations of catalytic-type proteasome subunits in vertebrates: Psmb5/Psmb8/Ps...

El momento en que el ser humano culmina una meta, es cuando se detiene a hacer un recuento de tod... more El momento en que el ser humano culmina una meta, es cuando se detiene a hacer un recuento de todas las ayudas recibidas, de las voces de aliento, de las expresiones de amor y comprensión; es por eso que nosotros dedicamos éste triunfo estudiantil a nuestros queridos padres quienes con su infinita adhesión nos han brindado todo su apoyo sin escatimar sacrificio alguno, gracias al Dr. Jorge Banegas Zambrano, mi padre, gracias Lcda. Ruby Andrade Yépez, mi madre, quienes siempre a mi lado han estado.

En la ciudad posmoderna

Cuadernos Hispanoamericanos, 2005

Marco conceptual de la educación médica en la América Latina

Ops Serie Desarrollo De Recursos Humanos, 1979

... JORGE ANDRADE EN SU DILATADA CARRERA-COMO PROFESOR Y DIRECTIVO DE LA FACULTAD DE MEDICINA DE ... more ... JORGE ANDRADE EN SU DILATADA CARRERA-COMO PROFESOR Y DIRECTIVO DE LA FACULTAD DE MEDICINA DE LA UNIVERSIDAD DE MEDICINA DE LA UNIVERSIDAD CENTRAL DE VENEZUELA Y COMO FUNCIONARIO DE LA DIVISION DE RECURSOS ...

CHAPTER 1 3.3.7 Does the Zrsr1 protein interact with U2AF 65 ? 80 3.3.8 Expression and Purificati... more CHAPTER 1 3.3.7 Does the Zrsr1 protein interact with U2AF 65 ? 80 3.3.8 Expression and Purification of recombinant U2AF-family members in E.coli 80 3.3.9 Expression and purification of recombinant proteins in HEK293T cells 86 3.3.10 Zrsr1interacts with U2AF 65 and associates with spliceosomal components 3.3.11 Subcellular localization of the Zrsr1 protein in MEL cells 92 3.3.12 The Zrsr1 gene is required for normal erythropoiesis 94 3.3.13 Erythroid-specific alternative splicing decisions are altered in Zrsr1-deficient mice 3.4 Discussion CHAPTER 4 4.1 Concluding Remarks and Future Perspectives 105 4.1 Concluding Remarks and Future Perspectives 106 4.1.1 Why splicing factors may regulate alternative splicing in a tissue-specific manner? 107 4.1.2 Is there a link between histone modifications and splicing? 109 4.1.3 Subcellular localization: a way to control the U2AF-related proteins function? 111 4.1.4 The role of Zrsr1 in erythropoiesis 112

Carta de Argentina. Vida de náufragos

Cuadernos Hispanoamericanos, 2002