A5023499384- Chromatin Remodeling and Cancer
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- Mechanisms of cancer metastasis
- DNA Repair Mechanisms
- Brain Metastases and Treatment
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Metabolism, Diabetes, and Cancer
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Machine Learning in Bioinformatics
- Lung Cancer Research Studies
The University of Texas MD Anderson Cancer Center
2023-2025
Anderson University - South Carolina
2024
Brain metastases in esophageal adenocarcinoma (EAC) patients are associated with poor prognosis and remain understudied. We performed multi-omics analysis whole-genome sequencing single-cell spatial transcriptomics on the brain matched primary tumors. Our identified ERBB2 as a recurrent oncogene EAC metastases, 9 out of 10 cases harboring amplifications. Single-cell multi-region revealed that alterations, occur early during disease progression monoclonal seeding. Although median survival our...
Abstract Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy dismal prognosis. Here, we corroborated findings by using immune-humanized, syngeneic, genetically engineered mouse models cancer harboring deficiency. Specifically, with loss showed decreased response anti-PD1...
Genomic studies have identified frequent mutations in subunits of the SWI/SNF (switch/sucrose non-fermenting) chromatin remodeling complex including SMARCA4 and ARID1A non-small cell lung cancer (NSCLC). Genetic evidence indicates that paralog SMARCA2 is synthetic lethal to suggesting a valuable therapeutic target. However, discovery selective inhibitors has been challenging. Here, we utilized structure-activity relationship (SAR) develop YD23, potent proteolysis targeting chimera (PROTAC)...
Abstract It is unclear how cells counteract the potentially harmful effects of uncoordinated DNA replication in context oncogenic stress. Here, we identify WRAD (WDR5/RBBP5/ASH2L/DPY30) core as a modulator pancreatic ductal adenocarcinoma (PDAC) models. Molecular analyses demonstrated that interacts with replisome complex, disruption DPY30 resulting re-replication, damage, and chromosomal instability (CIN) without affecting cancer cell proliferation. Consequently, immunocompetent models,...
Summary Genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A non-small cell lung cancer. Previously, we others that -mutant cancers are highly dependent on oxidative phosphorylation (OXPHOS). Despite initial excitements, therapeutics targeting metabolic pathways such as OXPHOS largely been disappointing due to rapid adaptation cancer cells inhibition single enzymes or pathways, suggesting novel combination...
Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung but data from these are disparate, siloed, difficult compare in a centralized fashion. Here we established Cancer Mouse Model Database (LCMMDB), an extensive repository 1,354 samples 77 transcriptomic datasets covering 974 genetically engineered (GEMMs), 368 carcinogen-induced models, 12 spontaneous model....
Abstract The SWI/SNF chromatin remodeling complex is frequently mutated in non-small cell lung cancer with a frequency of 33% advanced stage disease, making it the most commonly altered cancer. Among various subunits complex, SMARCA4 and ARID1A are by far mutated. Importantly, multiple clinical reports have shown that mutant cancers one worst prognosis among genetically defined subtypes lack response to both immunotherapy KRAS G12C inhibitors. Recent reports, our own data, identified...
Abstract Lung cancer is the top cause of mortality. Despite recent advances, majority patients with lung still lack effective therapeutic options, underscoring dire need for additional treatment approaches. Genomic studies have identified frequent mutations in subunits SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A non-small cell a frequency up to 33% advanced stage disease, making it most frequently mutated cancer. Previous work our lab, as well others, metabolic...
Abstract Cancer genomic studies have identified frequent alterations in components of the SWI/SNF (SWItch/Sucrose Non- Fermenting) chromatin remodeling complex including SMARCA4 and ARID1A . Importantly, clinical reports indicate that -mutant lung cancers respond poorly to immunotherapy dismal prognosis. However, mechanistic basis resistance is unknown. Here, we corroborated findings by using immune-humanized, syngeneic, genetically engineered mouse models cancer harboring deficiency....
ABSTRACT Cancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex including SMARCA4 non-small cell lung cancer with a frequency up to 33% advanced stage disease, making it most frequently mutated cancer. We and others SMARCA2 be synthetic lethal SMARCA4, indicating is high value therapeutic target. Here, we disclose discovery characterization potent, selective orally bioavailable Cereblon-based PROTACs. Biochemically, YDR1 YD54 are...
Abstract Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized non-humanized mice delineate potential mechanisms. No new EGFR mutations or loss of the T790M mutation found clones. Resistant tumors grown under continuous pressure both show aggressive tumor regrowth which is significantly less as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) identified a driver resistance, its selective inhibition...
Abstract Lung cancer is the top cause of mortality. Despite recent advances, majority patients with lung still lack effective therapeutic options, underscoring dire need for additional treatment approaches. Genomic studies have identified frequent mutations in subunits SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A non-small cell a frequency up to 33% advanced stage disease, making it most frequently mutated cancer. Recent reports, our own data, paralogue SMARCA2 be...
Abstract Lung cancer is the top cause of mortality. Despite recent advances, majority patients with lung still lack effective therapeutic options, underscoring dire need for additional treatment approaches. Genomic studies have identified frequent mutations in subunits SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A non-small cell a frequency up to 33% advanced stage disease, making it most frequently mutated cancer. Recent reports, as well our own data, paralogue SMARCA2...