A5049172617- Cancer Genomics and Diagnostics
- Wnt/β-catenin signaling in development and cancer
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Mechanisms of cancer metastasis
- Digestive system and related health
- Virus-based gene therapy research
- Bioinformatics and Genomic Networks
- Nutrition, Genetics, and Disease
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Polyamine Metabolism and Applications
- RNA regulation and disease
- BRCA gene mutations in cancer
- Berberine and alkaloids research
- RNA modifications and cancer
- DNA Repair Mechanisms
- Cytomegalovirus and herpesvirus research
- Biochemical and Molecular Research
- bioluminescence and chemiluminescence research
- Cancer therapeutics and mechanisms
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
Cornell University
2018-2023
Weill Cornell Medicine
2018-2023
University of Chicago
2021-2023
Abstract KRAS is the most frequently mutated oncogene in cancer, yet there little understanding of how specific amino acid changes affect tumor initiation, progression, or therapy response. Using high-fidelity CRISPR-based engineering, we created an allelic series new LSL-Kras mutant mice, reflecting codon 12 and 13 mutations that are highly prevalent lung (KRASG12C), pancreas (KRASG12R), colon (KRASG13D) cancers. Induction each allele either murine revealed striking quantitative qualitative...
Abstract The majority of colorectal cancers show hyperactivated WNT signaling due to inactivating mutations in the adenomatous polyposis coli (APC) tumor suppressor. Genetically restoring APC suppresses and induces rapid sustained regression, implying that reengaging this endogenous tumor-suppressive mechanism may be an effective therapeutic strategy. Here, using new animal models, human cell lines, ex vivo organoid cultures, we tankyrase (TNKS) inhibition can control hyperactivation provide...
Abstract Base editing (BE) is a powerful tool for engineering single nucleotide variants (SNVs) and has been used to create targeted mutations in cell lines, organoids animal models. Recent development of new BE enzymes provided an extensive toolkit genome modification; however, identifying isolating edited cells analysis proven challenging. Here we report ‘Gene On’ (GO) reporter system that indicates precise cytosine or adenine base situ with high sensitivity specificity. We test GO using...
Hyperactive WNT signaling is a potent cancer driver, but clinical translation of inhibitors has been hampered on-target toxicities. can be constrained through inhibition the PARP family enzymes Tankyrase 1 (TNKS1) and 2 (TNKS2), however, existing TNKS suppress in both tumor healthy tissues. In this study, we show that loss chromosome 8p occurs approximately half advanced epithelial malignancies, creates collateral vulnerability enables tumor-selective activity. depletes expression TNKS1...
ABSTRACT Base editing (BE) is a powerful tool for engineering single nucleotide variants (SNVs) and has been used to create targeted mutations in cell lines, organoids, animal models. Recent development of new BE enzymes provided an extensive toolkit genome modification; however, identifying isolating edited cells analysis proven challenging. Here we report “Gene On” (GO) reporter system that indicates precise cytosine or adenine base situ with high sensitivity specificity. We test GO using...
ABSTRACT Single nucleotide variants (SNVs) comprise the majority of cancer-associated genetic changes and can have diverse effects on protein function. Despite a comprehensive catalogue SNVs across human cancers, little is known about their impact tumor initiation progression. To enable functional interrogation SNVs, we developed murine system for temporal regulatable in vivo cytosine base editing (iBE). The iBE mice show robust, doxycycline-dependent expression broad range tissues with no...
We investigated a Spanish and Catalan family in which multiple cancer types tracked across three generations, but for no genetic etiology had been identified. Whole-exome sequencing of germline DNA from affected members was performed to identify candidate variants explain this occurrence familial cancer. discovered all cancer-affected single rare heterozygous variant (I654V, rs1801201) ERBB2/HER2, is located transmembrane glycine zipper motif critical ERBB2-mediated signaling complete...
<p>Supplementary Figures 1-14</p>
<p>Supplementary Figures and legends</p>