A5026087488- Chromatin Remodeling and Cancer
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Bioinformatics and Genomic Networks
- Endoplasmic Reticulum Stress and Disease
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Signaling Pathways in Disease
- RNA regulation and disease
- Lung Cancer Treatments and Mutations
- Protein Tyrosine Phosphatases
- Epigenetics and DNA Methylation
- Head and Neck Cancer Studies
- Gene expression and cancer classification
- PI3K/AKT/mTOR signaling in cancer
- Ovarian cancer diagnosis and treatment
- Genetic factors in colorectal cancer
- Cancer Mechanisms and Therapy
- Biochemical and Molecular Research
- Cancer Immunotherapy and Biomarkers
- Colorectal and Anal Carcinomas
- Advanced Breast Cancer Therapies
- Plant Disease Resistance and Genetics
- Gene Regulatory Network Analysis
The University of Texas MD Anderson Cancer Center
2014-2024
University of California, San Diego
2015-2023
Johns Hopkins University
2022-2023
Johns Hopkins Medicine
2022
ASML (Netherlands)
2021
La Jolla Bioengineering Institute
2018
Albany Medical Center Hospital
2018
Mount Sinai Hospital
2018
Centre for Addiction and Mental Health
2018
University of Toronto
2018
Appendiceal neoplasms are heterogeneous and often treated with chemotherapy similarly to colorectal cancer (CRC). Genomic profiling was performed on 703 appendiceal specimens compare the mutation profiles of subtypes CRC other cancers, ultimate aim identify potential biomarkers novel therapeutic targets.Tumor were submitted a Clinical Laboratory Improvement Amendments-certified laboratory (Foundation Medicine, Cambridge, MA) for hybrid-capture-based sequencing 3,769 exons from 315...
Src homology 2 domain-containing phosphatase (SHP2) is a that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and required for full activation the MAPK pathway. SHP2 inhibition has demonstrated tumor growth in RTK-activated cancers preclinical studies. The long-term effectiveness kinase inhibitors such as EGFR inhibitor (EGFRi), osimertinib, non-small cell lung cancer (NSCLC) limited by acquired resistance. Multiple clinically identified mechanisms underlie...
Abstract Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR–Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate renal tumors. Disruption 9p21 locus is an evolutionary driver systemic disease through the rapid acquisition complex karyotypes cancer cells. Cross-species analysis revealed recurrent patterns copy number variations, including 21q loss and dysregulation...
Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) represents a distinct classification of cancer with worse expected outcomes. Of the 11 genes recurrently mutated in HNSCC, we identify singular substantial survival advantage for mutations gene encoding Nuclear Set Domain Containing Protein 1 (NSD1), histone methyltransferase altered approximately 10% patients. This effect, 55% decrease risk death NSD1-mutated versus non-mutated patients, can be validated an...
Cellular dedifferentiation is a key mechanism driving cancer progression. Acquisition of mesenchymal features has been associated with drug resistance, poor prognosis, and disease relapse in many tumor types. Therefore, successful targeting tumors harboring these characteristics priority oncology practice. The SWItch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complex also emerged as critical player progression, leading to the identification several SWI/SNF genes potential...
We present an accessible, fast, and customizable network propagation system for pathway boosting interpretation of genome-wide association studies. This system-NAGA (Network Assisted Genomic Association)-taps the NDEx biological resource to gain access thousands protein networks select those most relevant performative a specific study. The method works efficiently, completing analysis in under 5 minutes on modern laptop computer. show that NAGA recovers many known disease genes from...
In patients with metastatic colon cancer, response to first line chemotherapy is a strong predictor of overall survival (OS). Currently, oncologists lack diagnostic tests determine which regimen offers the greatest chance for in an individual patient. Here we present results gene expression analysis two genes, ERCC1 and TS, measured commercially available ResponseDX: Colon assay (Response Genetics, Los Angeles, CA) 41 de novo cancer diagnosed between July 2008 August 2013 at University...
We present pyNBS: a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes. In addition to release software, we benchmark its key parameters provide compact cancer reference network that increases significance using NBS algorithm. The structure code exposes steps foster further collaborative development.The package, along with examples data, can be downloaded...
Many recent efforts to analyze cancer genomes involve aggregation of mutations within reference maps molecular pathways and protein networks. Here, we find these pathway studies are impeded by interactions that functionally irrelevant or the patient's tumor type, as diminish contrast driver relative individual frequently mutated genes. This problem can be addressed creating stringent tumor-specific networks biophysical interactions, identified signatures epistatic selection during evolution....
Mutated KRAS protein is a pivotal tumor driver in pancreatic cancer. However, despite comprehensive efforts, effective therapeutics that can target oncogenic are still under investigation or awaiting clinical approval. Using specific KRAS-dependent gene signature, we implemented computer-assisted inspection of drug-gene network to silico repurpose drugs work like inhibitors KRAS. We identified and validated decitabine, an FDA-approved drug, as potent inhibitor growth cancer cells...
Abstract Background: The high mortality rate of colorectal cancer (CRC) is primarily due to metastatic disease. Microscopic minimal residual disease (MRD) detected in patients by circulating tumor DNA (ctDNA) may remain radiographically undetectable and persist following therapeutic intervention, resulting recurrence. Preclinical models are urgently needed elucidate the mechanisms whereby MRD escapes anti-tumor immune surveillance. We have developed characterized a preclinical liver model...
Abstract Gene networks are rapidly growing in size and number, raising the question of which most appropriate for a particular application. Here, we evaluate 21 human genome-wide interaction their ability to recover gene sets associated with 446 different diseases 9 cancer hallmarks. While all have some these recovery tasks, observe wide range performance STRING, GeneMANIA GIANT having best overall. A general tendency is that scales network size, suggesting new discovery currently outweighs...
Abstract Dedifferentiation and acquisition of chromosomal instability in renal cell carcinoma portends dismal prognosis aggressive clinical behavior. However, the absence reliable experimental models dramatically impacts understanding mechanisms underlying malignant progression. Here we established an vivo genetic platform to rapidly generate somatic mosaic genetically engineerd immune-competent mouse tumors, recapitulating genomic phenotypic features these malignancies. Leveraging...
Abstract Osimertinib, a third generation EGFR inhibitor, is front-line therapy for mutated non-small lung cancer (NSCLC). The long-term effectiveness of osimertinib limited by acquired resistance. Clinically identified resistance mechanisms include EGFR-dependent such as mutations on that preclude drug binding, and EGFR-independent activation the MAPK pathway, instance via alternate RTKs. It has also been noted frequently tumor from single patient harbors more than one mechanism, plasticity...
An after etch overlay measurement on device is typically used as a reference this what determines the final overlay. The delta between target from develop (ADI) and (AEI) known metrology to offset (MTD). As fab controlled by run-to-run control of ADI overlay, it preferred minimize MTD. MTD concept in has long been present industry many ways mitigate problem have adopted (such designing at that similarly low aberration response device, or dialing static AEI etc.). margins continue shrink,...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal adult cancers with an average 5-year survival rate less than 10% due in part to limited number effective therapies. Activation TRAILR2 (Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand Receptor 2) has emerged as important therapeutic concept cancer treatment. Traditional agonists have had clinical success lack efficacy or, importantly, severe hepatotoxicity. Here we present anti-tumor activity preclinical...
<p>Supplementary Figure 1. Characterization of 23 PDAC cell lines.</p>