A5060805275- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Cytokine Signaling Pathways and Interactions
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- Genomics and Rare Diseases
- Evolution and Genetic Dynamics
- Renal cell carcinoma treatment
- Genetics, Bioinformatics, and Biomedical Research
- Melanoma and MAPK Pathways
- Nutrition, Genetics, and Disease
- Ubiquitin and proteasome pathways
- Chromosomal and Genetic Variations
- Cutaneous Melanoma Detection and Management
- Molecular Biology Techniques and Applications
- Lung Cancer Treatments and Mutations
Northwestern University
2018-2023
Broad Institute
2011-2023
Massachusetts General Hospital
2016-2023
Shaoyang University
2022-2023
Anhui Polytechnic University
2020-2023
Affiliated Hospital of Southwest Medical University
2022
Wuhan University of Technology
2021
Memorial Sloan Kettering Cancer Center
2017-2020
Midwestern University
2019
Yangzhou University
2019
Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns and epigenetic phenotypes not yet clear. We analyzed genomes 200 clinically annotated adult cases de novo AML, using either whole-genome sequencing (50 cases) or whole-exome (150 cases), along with RNA microRNA DNA-methylation analysis. AML have fewer than most other cancers, an average only 13 found in genes. Of these, 5 genes recurrently mutated AML. A total...
Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths 2008 alone. This malignancy represents a heterogeneous group tumours characteristic molecular features, prognosis responses to available therapy. Recurrent somatic alterations breast cancer have been described, including mutations copy number alterations, notably ERBB2 amplifications, first successful therapy target defined by genomic aberration....
To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant DLBCL, including MYD88 , CARD11 EZH2 CREBBP . also somatic for which a functional role has not been previously suspected. These include MEF2B MLL2 BTG1 GNA13 ACTB P2RY8 PCLO TNFRSF14 Further,...
Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely mutations in BTK and related pathway molecules. Using whole-exome deep-targeted sequencing, we dissect evolution of resistance serial samples from five chronic lymphocytic leukaemia patients. In two patients, detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion clones harbouring del(8p) with additional driver (EP300, MLL2 EIF2A), one patient...
Recent studies of cellular networks have revealed modular organizations genes and proteins. For example, in interactome networks, a module refers to group interacting proteins that form molecular complexes and/or biochemical pathways together mediate biological process. However, it is still poorly understood how information transmitted between different modules. We developed flow analysis, new computational approach identifies central the transmission throughout network. In we represent an...
Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and function these alleles remains undefined. We have developed a scalable systematic approach to interrogate cancer-associated gene variants. subjected 474 mutant curated from 5,338 tumors pooled vivo tumor formation assays expression profiling. identified 12 transforming alleles, including two genes (PIK3CB, POT1) that not...
Resistance to anoikis, the subtype of apoptosis triggered by lack adhesion, contributes malignant transformation and development metastasis. Although several lines evidence suggest that p53 plays a critical role in pathway(s) connect cell detachment remain undefined. Here, through use kinome-wide loss-of-function screen, we identify serine-threonine kinase SIK1 (salt-inducible 1) as regulator p53-dependent anoikis. Inactivation compromised function anoikis allowed cells grow an...
Breast cancer is often associated with inappropriate activation of transcription factors involved in normal mammary development. Two related factors, signal transducer and activator (STAT) 5 STAT3, play important distinct roles development both can be activated breast cancer. However, the relative contribution these STATs to tumorigenesis unknown. We have found that primary human tumors displaying are more differentiated than those STAT3 alone display favorable prognostic characteristics. To...
The tet methylcytosine dioxygenase 2 (TET2) enzyme catalyzes the conversion of modified DNA base 5-methylcytosine to 5-hydroxymethylcytosine. TET2 is frequently mutated or dysregulated in multiple human cancers, and loss associated with changes methylation patterns. Here, using newly developed TET2-specific antibodies estrogen response as a model system for studying regulation gene expression, we demonstrate that endogenous occupies active enhancers facilitates proper recruitment receptor α...
Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway understand underlying mechanisms. can be either intrinsic or acquired. We derived series of subcloned MCF7 cell lines that were highly sensitive naturally resistant studied the factors lead drug resistance. Gene-expression studies revealed signature 67 genes differentially respond vs. subclones, which also predicts disease-free survival tamoxifen-treated patients. High-throughput...
Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months completing RT. No further clinical benefit achieved using alternative radiation strategies. Here, we tested hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in DIPG.Experimental Design: We evaluated effects on genes...
Significance DOT1L is a histone methyltransferase that catalyzes H3K79 methylation, chromatin modification correlated with active transcription. Inhibition of DOT1L’s catalytic activity has been studied for cancer therapy; however, the mechanisms underlying its function in development and pathogenesis remain elusive. To understand catalytic-dependent catalytic-independent functions DOT1L, we generated dead null embryonic stem cells found but not activity, required establishing proper...
Background Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets therapeutic intervention since this property is believed to be critical displaced from their natural niches. Anchorage-independent induced by growth factor receptor hyperactivation in many cell types. We aimed identify molecules critically regulate IGF-1-induced survival. Methods and Results conducted a high-throughput siRNA screen identified PTK6 as component IGF-1...
The rice black-streaked dwarf virus (RBSDV) disease causes severe yield losses in Eastern China and other East Asian countries. Breeding resistant cultivars is the most economical effective strategy to control disease. However, few varieties QTLs for RBSDV resistance have been identified date. In this study, we conducted a genome-wide association study (GWAS) on using diversity panel 1 (RDP1) that were genotyped by 44,000 high-density single nucleotide polymorphism (SNP) markers array. We...