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My lab will develop genetic models of liver and lung cancer using small RNA tools, such as RNAi-mediated silencing and CRISPR/Cas9-mediated genome editing. The CRISPR/Cas9 system allows us to quickly generate somatic loss-of-function mutations in tumor suppressor genes or gain-of-function mutations in oncogenes. Our approach presents a new avenue for rapid development of cancer models, functional genomics, and proof-of-concept targeted cancer therapy. My laboratory will engage in the following areas of research over the next few years:

Discover and correct liver cancer genes using CRISPR-mediated genome editing

Many candidate cancer genes are being discovered through cancer genome-sequencing efforts, and simple genetic methods are needed to validate candidate cancer genes in vivo. CRISPR/Cas genome-editing has been successfully used in many organisms, including mouse and human cells. We will use in vivo CRISPR/Cas-mediated genome editing tools to discover, validate, and correct liver cancer genes in the mouse. To identify potential liver cancer therapeutic targets, we will devise novel CRISPR strategies to delete candidate oncogenes and test the effect on liver cancer progression. Because our approach allows us to perform genetic tests without breeding mice, our approach will speed up cancer gene discovery and drug target validation for liver cancer.

Characterize response and resistance to KRAS inhibition using in vivo RNAi and genome editing

KRAS is mutated in >30% of lung cancer. While most studies in the literature use inducible Kras cDNA, conditional shRNA system allows knockdown of endogenous levels of Kras in vivo, offering a more physiologic model of Kras inhibition. We will model the response and resistance to Kras inhibition in mouse models using lentiviral-based tet-on shRNA in the lung. Our recent studies show that after long-term Kras inhibition by RNAi, Kras-driven tumors relapse and become Kras-independent. We will explore the molecular basis of resistance to Kras inhibition using gene expression profiling. To completely delete the oncogenic KRAS gene and compare the phenotype with RNAi-mediated knockdown, we plan to use CRISPR to generate floxed KRAS conditional knockout alleles in lung cancer cell lines. These small RNA-based experiments will generate in vivo and in vitro platforms to uncover important KRAS biology.

Investigate oncogenic and tumor suppressor miRNA networks in lung cancer

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate mRNA translation or stability. Delineating miRNA networks can identify new miRNAs and miRNA antagonists for lung cancer treatment. We will cross-compare human lung adenocarcinoma miRNA expression profiles and cancer genome copy number analyses from TCGA (the Cancer Genome Atlas) to identify candidate miRNAs that drive or suppress tumor formation. We will use tet-on miRNA expression system to conditionally express miRNA at various stages of tumor progression and study the impact on tumor growth in vivo. Together, these studies will unveil miRNA networks in cancer using genetic tools.  

Post Docs

We are looking for postdoc candidates with experience in cancer biology, mouse models and genome-engineering. Please email CV and 3 letters of recommendation to Wen.Xue@umassmed.edu.

Rotation Projects

Our lab uses CRISPR tools to speed up cancer gene discovery and disease gene repair. Rotation projects are available to explore experimental techniques such as molecular cloning of CRISPR plasmids, measuring genome-editing efficiency, dissecting mice, and processing of mouse tumor/tissue for histology.

One or more keywords matched the following items that are connected to Xue, Wen
Item TypeName
Concept Lung Neoplasms
Concept Bile Duct Neoplasms
Concept Liver Neoplasms
Concept Liver Neoplasms, Experimental
Concept Neoplasms
Concept Colonic Neoplasms
Academic Article CRISPR-mediated direct mutation of cancer genes in the mouse liver.
Academic Article Small RNA combination therapy for lung cancer.
Academic Article KRAS and YAP1 converge to regulate EMT and tumor survival.
Academic Article p53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer.
Academic Article A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions.
Academic Article An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer.
Academic Article Topoisomerase levels determine chemotherapy response in vitro and in vivo.
Academic Article DLC1 is a chromosome 8p tumor suppressor whose loss promotes hepatocellular carcinoma.
Academic Article Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas.
Academic Article Mouse genomic representational oligonucleotide microarray analysis: detection of copy number variations in normal and tumor specimens.
Academic Article Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach.
Academic Article Response and resistance to NF-?B inhibitors in mouse models of lung adenocarcinoma.
Academic Article Rapid modelling of cooperating genetic events in cancer through somatic genome editing.
Academic Article Reciprocal interaction of Wnt and RXR-? pathways in hepatocyte development and hepatocellular carcinoma.
Academic Article IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis.
Academic Article Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma.
Academic Article Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors.
Academic Article Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology.
Academic Article Precision cancer mouse models through genome editing with CRISPR-Cas9.
Award or Honor Receipt Scientific Merit Award
Award or Honor Receipt Session co-chair
Award or Honor Receipt Research Scholars Grant
Academic Article Genomic Amplifications Cause False Positives in CRISPR Screens.
Award or Honor Receipt Research fund
Award or Honor Receipt Pediatric Cancer Grant
Academic Article Genome-Wide CRISPR Screen Identifies Regulators of Mitogen-Activated Protein Kinase as Suppressors of Liver Tumors in Mice.
Academic Article Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis.
Academic Article Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma.
Academic Article A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma.
Academic Article CRISPR-Cas-related technologies in basic and translational liver research.
Academic Article The search for precision models clinically relevant to human liver cancer.
Grant An integrative approach to study KRAS inhibition in lung cancer
Academic Article Targeted Metabolomics Identifies the Cytochrome P450 Monooxygenase Eicosanoid Pathway as a Novel Therapeutic Target of Colon Tumorigenesis.
Academic Article CRISPR-SONIC: targeted somatic oncogene knock-in enables rapid in vivo cancer modeling.
Academic Article p53 Represses the Mevalonate Pathway to Mediate Tumor Suppression.
Academic Article Depletion of TRRAP Induces p53-Independent Senescence in Liver Cancer by Down-Regulating Mitotic Genes.
Academic Article YAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte-Like Cells.
Academic Article Targeting the De Novo Purine Synthesis Pathway Through Adenylosuccinate Lyase Depletion Impairs Liver Cancer Growth by Perturbing Mitochondrial Function.
Academic Article Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice.
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  • Cancers