A5067535832- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Testicular diseases and treatments
- Sepsis Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Sarcoma Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Immune Response and Inflammation
- Respiratory Support and Mechanisms
- Protein Degradation and Inhibitors
- Renal and related cancers
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Chromatin Remodeling and Cancer
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Gestational Trophoblastic Disease Studies
- Cancer Cells and Metastasis
- Molecular Biology Techniques and Applications
- Genetic Syndromes and Imprinting
- Adrenal Hormones and Disorders
- Bioinformatics and Genomic Networks
- Cancer Mechanisms and Therapy
Northwestern University
2019-2024
Midwestern University
2019
The University of Texas Southwestern Medical Center
2017-2018
Children's Medical Center
2018
Objective The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes patients with hepatocellular carcinoma (HCC). We sought develop non-invasive approach using circulating cell-free DNA (cfDNA) for early detection HCC. Design Applying 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2554 Chinese subjects: 1204 HCC, 392 chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC) 958...
OBJECTIVES: Untangling the heterogeneity of sepsis in children and identifying clinically relevant phenotypes could lead to development targeted therapies. Our aim was analyze organ dysfunction trajectories with sepsis-associated multiple syndrome (MODS) identify reproducible determine if they are associated treatment effect (HTE) common DESIGN: Multicenter observational cohort study. SETTING: Thirteen PICUs United States. PATIENTS: Patients admitted suspected infections PICU between 2012...
Abstract Studies have revealed dozens of functional peptides in putative ‘noncoding’ regions and raised the question how many proteins are encoded by noncanonical open reading frames (ORFs). Here, we comprehensively annotate genome-wide translated ORFs across five eukaryotes ( human , mouse zebrafish worm yeast ) analyzing ribosome profiling data. We develop a logistic regression model named PepScore based on ORF features (expected length, domain, conservation) to calculate probability that...
<h3>Importance</h3> Multiple organ dysfunction syndrome (MODS) is a dynamic and heterogeneous process associated with high morbidity mortality in critically ill children. <h3>Objective</h3> To determine whether data-driven phenotypes of MODS based on the trajectories 6 dysfunctions have prognostic therapeutic relevance <h3>Design, Setting, Participants</h3> This cohort study included 20 827 pediatric intensive care encounters among 14 285 children admitted to 2 large academic units (PICUs)...
Abstract The genomic distribution of cleavage and polyadenylation (polyA) sites should be co-evolutionally optimized with the local gene structure. Otherwise, spurious can cause premature transcription termination generate aberrant proteins. To obtain mechanistic insights into polyA site optimization across human genome, we develop deep/machine learning models to identify genome-wide putative at unprecedented nucleotide-level resolution calculate their strength usage in context. Our...
We describe a low-input RNase footprinting approach for the rapid quantification of ribosome-protected fragments with as few 1000 cultured cells. The assay uses simplified procedure to selectively capture ribosome footprints based on optimized digestion. It simultaneously maps cytosolic and mitochondrial translation single-nucleotide resolution. applied it reveal selective functions elongation factor TUFM in translation, well synchronized repression after perturbation. show is applicable...
Many childhood Wilms tumors are driven by mutations in the microRNA biogenesis machinery, but mechanism which these drive tumorigenesis is unknown. Here we show that transcription factor pleomorphic adenoma gene 1 (PLAG1 ) a target overexpressed with processing genes. can also overexpress PLAG1 through copy number alterations, and expression correlates prognosis tumors. overexpression accelerates growth of tumor cells vitro induces neoplastic developing mouse kidney vivo. In both settings,...
Germ cell tumors (GCT) are malignant that arise from pluripotent embryonic germ cells and occur in children young adults. GCTs treated with cisplatin-based regimens which, while overall effective, fail to cure all patients cause significant adverse late effects. The seminoma nonseminoma forms of GCT exhibit distinct differentiation states, clinical behavior, response treatment; however, the molecular mechanisms not fully understood. We tested whether activity mTORC1 MAPK pathways were...
DICER1 syndrome1 predisposes to a variety of cancers, including pleuropulmonary blastoma (PPB),2 ovarian Sertoli-Leydig cell tumor (SLCT),3 embryonal rhabdomyosarcoma,4 and kidney tumors.5–8 In syndrome, most patients bear germline null mutation in DICER1, the tumors uniformly second-hit missense substitution at one five hotspot positions (1705E, 1709D, 1809G, 1810D, 1813E). A wide range clinical phenotypes can be seen syndrome5,9; some are asymptomatic, whereas others develop multiple...
The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. In different genetically engineered mouse models tumor-expressed CD95 was shown to be critical for cell growth. Using a combination of immune-deficient and immune-competent models, we now establish that loss in metastatic triple negative breast cancer (TNBC) cells prevents tumor growth by modulating the immune landscape. CD95-deficient, but not wild-type, tumors barely grow an environment show increase infiltrates...
3'-end cleavage and polyadenylation is an essential process for eukaryotic mRNA maturation. In yeast species, the signals that recruit processing machinery are degenerate remain poorly characterized compared with well-defined regulatory elements in mammals. Here we address this issue by developing deep learning models to deconvolute
Abstract Ribosome profiling isolates ribosome‐protected fragments for sequencing and is a valuable method studying different aspects of RNA translation. However, conventional protocols require millions input cells time‐consuming steps to isolate translating ribosome complexes using ultracentrifugation or immunoprecipitation. These limitations have prevented their application rare physiological samples. To address these technical barriers, we developed an RNase footprinting approach named...
BackgroundIdentifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these to specific patient populations is unclear. Given that paediatric cancer with have different host response and pathogen profiles higher mortality rates when compared non-cancer patients, we determined whether unique, reproducible, clinically-relevant exist this population.MethodsWe studied underlying malignancies admitted one 25 intensive care units (PICUs)...
Abstract Background Wilms tumor and rhabdoid can have similar clinical presentations, but they distinct histological biological features. For instance, tumors commonly bear mutations in kidney differentiation or microRNA processing genes, whereas is characterized by loss of SMARCB1 . Aims We initially set out to characterize identify suppressor microRNAs WT‐CLS1, which had been described as a cell line. Methods Results the line WT‐CLS1 whole exome sequencing, RNA‐seq, xenograft histology....
Multiple organ dysfunction syndrome (MODS) is one of the most common causes death in critically ill children. However, despite decades clinical trials, there are no comprehensive approaches to management MODS or effective targeted therapies that have consistently improved outcomes. Better understanding heterogeneity and characterizing subgroups patients could improve our help us develop new strategies. We analyzed a cohort 5,297 children with from two children's hospitals used...
Abstract Studies have identified genes and molecular pathways regulating cancer metastasis. However, it remains largely unknown whether metastatic potentials of cells from different lineage types are driven by the same or gene networks. Here, we aim to address this question through integrative analyses 493 human cells’ transcriptomic profiles their in vivo. Using an unsupervised approach considering both coexpression protein–protein interaction networks, identify networks associated with...
Abstract The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. Stimulation by its cognate ligand CD95L on many cancer cells increases their growth, motility, ability to invade and/or stemness. Using genetically engineered mouse models of ovarian and liver cancer, we previously reported that deletion CD95 in the tumor strongly reduced grow vivo [1, 2]. a combination immune-deficient immune-competent models, now establish loss metastatic triple negative breast prevents...
Pancreatic adenocarcinoma is the most common malignancy of pancreas, accounting for about 85% all pancreatic cancer cases. Although it only 11th globally, comprises a disproportionate number total deaths. It ranks 7th worldwide mortality, responsible over 400,000 annual deaths globally. Though advances in research and clinical oncology have significantly improved patient outcomes many human cancers, prognosis remains dismal: ~5% would live five years after diagnosis. Early detection high...
<p>Supplementary Table 1. Combined immunohistochemistry scores, yolk sac tumor and seminoma Supplementary 2. Immunohistochemistry scores for all tumors 3. Sequences of primers used quantitative RT-PCR Figure Complete blots NCCIT NTERA-2 cells treated with ligands. See 4A more details. rapamycin. 5 erlotinib. 4. Effect EGFR mTORC1 inhibitors on the viability cells. 5. Model depicting signaling pathways inhibited by erlotinib rapamycin in NSGCTs</p>
<div>Abstract<p>Germ cell tumors (GCT) are malignant that arise from pluripotent embryonic germ cells and occur in children young adults. GCTs treated with cisplatin-based regimens which, while overall effective, fail to cure all patients cause significant adverse late effects. The seminoma nonseminoma forms of GCT exhibit distinct differentiation states, clinical behavior, response treatment; however, the molecular mechanisms not fully understood. We tested whether activity...
<p>Supplementary Table 1. Combined immunohistochemistry scores, yolk sac tumor and seminoma Supplementary 2. Immunohistochemistry scores for all tumors 3. Sequences of primers used quantitative RT-PCR Figure Complete blots NCCIT NTERA-2 cells treated with ligands. See 4A more details. rapamycin. 5 erlotinib. 4. Effect EGFR mTORC1 inhibitors on the viability cells. 5. Model depicting signaling pathways inhibited by erlotinib rapamycin in NSGCTs</p>
ABSTRACT 3’-end cleavage and polyadenylation is an essential process for eukaryotic mRNA maturation. In yeast species, the signals that recruit processing machinery are degenerate remain poorly characterized compared to well-defined regulatory elements in mammals. Especially, recent deep sequencing experiments showed extensive heterogeneity some mRNAs Saccharomyces cerevisiae uncovered polyA motif differences between S. vs. Schizosaccharomyces pombe . The findings raised fundamental question...
<div>Abstract<p>Germ cell tumors (GCT) are malignant that arise from pluripotent embryonic germ cells and occur in children young adults. GCTs treated with cisplatin-based regimens which, while overall effective, fail to cure all patients cause significant adverse late effects. The seminoma nonseminoma forms of GCT exhibit distinct differentiation states, clinical behavior, response treatment; however, the molecular mechanisms not fully understood. We tested whether activity...
ABSTRACT Background Rhabdoid tumor is a highly aggressive pediatric cancer characterized by biallelic loss and/or mutation of SMARCB1 . Outcomes remain poor, and there are no established ways to target the tumorigenic pathways driven inactivation. leads an increase in cyclin D transcription. Procedure We cell line WT-CLS1, which has been described previously as Wilms tumor, whole-exome sequencing, RNA-seq, xenograft histology. measured effect microRNA overexpression on BT-12, CHLA-06-ATRT....