A5086210274- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- Protein Degradation and Inhibitors
- Plant Virus Research Studies
- Histone Deacetylase Inhibitors Research
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Genomic variations and chromosomal abnormalities
- Molecular Biology Techniques and Applications
- Ubiquitin and proteasome pathways
- Childhood Cancer Survivors' Quality of Life
- Asthma and respiratory diseases
- Circadian rhythm and melatonin
- Acute Lymphoblastic Leukemia research
- RNA Research and Splicing
- Genomics and Rare Diseases
- Cystic Fibrosis Research Advances
- Acute Myeloid Leukemia Research
- Advanced biosensing and bioanalysis techniques
- Viral-associated cancers and disorders
Case Western Reserve University
2018-2025
University School
2023-2024
Case Comprehensive Cancer Center
2019
St. Jude Children's Research Hospital
2014-2016
Tulane University
2010-2013
Approaches to mitigate the severity of infections and immune responses are still needed for treatment cystic fibrosis (CF) even with success highly effective modulator therapies. Previous studies identified reduced levels melatonin in a CF mouse model related circadian rhythm dysregulation. Melatonin is known have immunomodulatory properties it was hypothesized that would improve bacterial infection mice. Data demonstrate mice (G542X/G542X) treated (10 µg/mL) drinking water 10 weeks had...
The TBX2 subfamily of T-box transcription factors (including Tbx2, Tbx3, Tbx4, Tbx5) plays an essential role in lung development. Downregulation these genes human Lung adenocarcinoma (LUAD) suggests that may be tumor suppressive, however because downregulation appears to occur primarily via epigenetic change, it remains unclear if changes causally drive progression or are merely the consequence upstream events. Herein, we developed first multiplexed mouse model study impact loss, alongside...
The World Health Organization and the U.S. Centers for Disease Control Prevention have reported that antibiotic resistant infections with Pseudomonas aeruginosa present a significant health risk world-wide. In genetic disease Cystic Fibrosis (CF), chronic lung persistent inflammation remain leading causes of morbidity mortality. While highly effective modulator therapy (HEMT) dramatically improves function in CF, they fail to eradicate or eliminate associated hyperinflammatory state. Thus,...
Despite progress in intensification of therapy, outcomes for patients with metastatic osteosarcoma (OS) have not improved thirty years. We developed a system that enabled preclinical screening compounds against OS cells the context native lung microenvironment. Using this strategy to screen library epigenetically targeted compounds, we identified inhibitors CDK12 be most effective, reducing cell outgrowth by more than 90% at submicromolar doses. found knockout an vivo model metastasis...
Commonly-mutated genes have been found for many cancers, but less is known about mutations in cis-regulatory elements. We leverage gains tumor-specific enhancer activity, coupled with allele-biased mutation detection from H3K27ac ChIP-seq data, to pinpoint potential enhancer-activating colorectal cancer (CRC). Analysis of a genetically-diverse cohort CRC specimens revealed that microsatellite instable (MSI) samples high indel rate within active enhancers. Enhancers indels show evidence...
Cells adapt to various chronic toxic exposures in a multitude of ways minimize further damage and maximize their growth potential. Expression L1 elements the human genome can be greatly deleterious cells, generating numerous double strand breaks (DSBs). have been reported respond DSBs by altering repair these breaks, including increasing rate homology independent DSB repair. Retrotransposition is strongly affected proteins involved Therefore, expression has potential source thus bring about...
Abstract The metastasis-invasion cascade describes the series of steps required for a cancer cell to successfully spread from its primary tumor and ultimately grow within secondary organ. Despite metastasis being dynamic, multistep process, most omics studies date have focused on comparing tumors metastatic deposits that define end-stage disease. This static approach means we lack information about genomic epigenomic changes occur during majority progression. One particularly understudied...
The non-long terminal repeat (non-LTR) retrotransposons, long interspersed element-1 (LINE-1) and Alu are currently active retroelements in humans. We, others, have observed that different populations of HeLa cells from laboratories support retrotransposition LINE-1 to varying degrees. We therefore tested whether individual cell clones HCT116 lines supported levels retrotransposition, these variations were stable upon re-cloning.Standard tissue culture assays used measure a cell's ability...
Abstract Lung adenocarcinoma (LUAD) is a multifaceted and genetically diverse cancer, shaped by myriad of oncogenic tumor suppressive events. Through recent clinical in vitro investigations, we have discovered that the TBX2 subfamily genes, encompassing TBX2, TBX3, TBX4, TBX5, are linked to LUAD progression. Specifically, observed marked downregulation their expression specimens, reduced growth cell lines when re-activated- hinting at potential function. Paradoxically, role genes other...
Abstract The metastasis-invasion cascade describes the series of steps required for a cancer cell to successfully spread from its primary tumor and ultimately grow within secondary organ. Despite metastasis being dynamic, multistep process, most omics studies date have focused on comparing tumors metastatic deposits that define end-stage disease. This static approach means we lack information about genomic epigenomic changes occur during majority progression. One particularly understudied...
Abstract Transposable elements become increasingly active in both cancerous and aging cells, driven by loss of DNA methylation as cells divide. Here we leverage the epigenomes colon cancers with matched adjacent tissue, addition to non-cancerous normals cell line models, assess role transposable drivers or passengers cancer development. Using baseline activity from normal show that youngest subfamilies LINE1 (L1) family exhibit a degree recurrence across patients goes beyond what is expected...
Abstract Lung adenocarcinoma (LUAD) is a complex cancer driven by diverse combinations of oncogenic and tumor suppressive events. The TBX2 subfamily genes, including TBX2, TBX3, TBX4, TBX5, are known to play crucial role in lung development as master transcriptional regulators. Our previous clinical vitro studies found that their expression significantly suppressed LUADs, suggesting potential suppressor through modulating methylation patterns early tumorigenesis. However, the genes other...
Abstract Commonly-mutated genes have been found for many cancers, but less is known about mutations in cis -regulatory elements. We leverage gains tumor-specific enhancer activity, coupled with allele-biased mutation detection from H3K27ac ChIP-seq data, to pinpoint potential enhancer-activating colorectal cancer (CRC). Analysis of a genetically-diverse cohort CRC specimens revealed that microsatellite instable (MSI) samples high indel rate within active enhancers. Enhancers indels show...
Abstract The metastasis-invasion cascade describes the series of steps required for a cancer cell to successfully spread from its primary tumor and ultimately grow within secondary organ. Despite metastasis being dynamic, multistep process, most omics studies date have focused on comparing tumors metastatic deposits that define end-stage disease. This static approach means we lack information about genomic epigenomic changes occur during majority progression. One particularly understudied...