- Planarian Biology and Electrostimulation
- Marine Ecology and Invasive Species
- Plant and Biological Electrophysiology Studies
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Cancer-related gene regulation
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- FOXO transcription factor regulation
- Cancer-related molecular mechanisms research
- Esophageal Cancer Research and Treatment
- Immune Cell Function and Interaction
- Chromatin Remodeling and Cancer
- Pancreatic and Hepatic Oncology Research
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Photoreceptor and optogenetics research
- Hydrogen's biological and therapeutic effects
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Neuroscience and Neural Engineering
University of Southern California
2022-2025
University of California, Merced
2020-2024
Cedars-Sinai Medical Center
2022-2023
Southern California University for Professional Studies
2023
Abstract Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate treatment resistance common. Improving the efficacy ICB requires better understanding mechanism immune evasion. Here, we identify that SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. inhibition leads to increased CD8 + T infiltration...
Histone modification H3K27me3 plays a critical role in normal development and is associated with various diseases, including cancer. This forms large chromatin domains, known as Large Organized Chromatin Lysine Domains (LOCKs), which span several hundred kilobases. In this study, we identify categorize LOCKs 109 human samples, distinguishing between long short LOCKs. Our findings reveal that are predominantly developmental processes, while enriched poised promoters most low gene expression....
Inactivation of the tumor suppressor genes protein p53 ( TP53 ) and cyclin-dependent kinase inhibitor 2A CDKN2A occurs early during gastroesophageal junction (GEJ) tumorigenesis. However, because a paucity GEJ-specific disease models, cancer-promoting consequences inactivation at GEJ have not been characterized. Here, we report development wild-type primary human organoid model CRISPR-edited transformed model. CRISPR-Cas9–mediated knockout TP53/CDKN2A KO in organoids induced morphologic...
Unlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify transcription factor (TF) FOXM1 as an important epigenetic regulator EAC. plays a critical role cellular proliferation and tumor growth EAC patient-derived organoids cell line models. We ERBB2 upstream expression transcriptional activity FOXM1. Unexpectedly, gene set enrichment analysis (GSEA)...
Abstract Background As one of the most common malignancies, esophageal cancer has two subtypes, squamous cell carcinoma and adenocarcinoma, arising from distinct cells-of-origin. Distinguishing cell-type-specific molecular features cancer-specific characteristics is challenging. Results We analyze whole-genome bisulfite sequencing data on 45 tumor nonmalignant samples both subtypes. develop a novel sequence-aware method to identify large partially methylated domains (PMDs), revealing...
ABSTRACT Nutrient availability upon feeding leads to an increase in body size the planarian Schmidtea mediterranea. However, it remains unclear how food consumption integrates with cell division at organismal level. Here, we show that NAD-dependent protein deacetylases sirtuins are evolutionarily conserved planarians, and specifically demonstrate homolog of human sirtuin-1 (SIRT1) (encoded by Smed-Sirt-1), regulates growth impairing both behavior intestinal morphology. Disruption Smed-Sirt-1...
Upper aerodigestive squamous cell carcinoma (UASCC) is a common and aggressive malignancy with few effective therapeutic options. Here, we investigate amino acid metabolism in this cancer, surprisingly noting that UASCC exhibits the highest methionine level across all human cancers, driven by its transporter LAT1. We show LAT1 also expressed at UASCC, transcriptionally activated UASCC-specific promoter enhancers, which are directly coregulated SCC master regulators TP63/KLF5/SREBF1....
Exposure to high levels of ionizing γ radiation leads irreversible DNA damage and cell death. Here, we establish that exogenous application electric stimulation enables cellular plasticity the re-establishment stem activity in tissues damaged by radiation. We show subthreshold direct current (DCS) rapidly restores pluripotent populations previously eliminated lethally γ-irradiated planarian flatworm Schmidtea mediterranea. Our findings reveal DCS enhances repair, transcriptional activity,...
In the planarian field, two techniques are mostly used for protein detection: immunohistochemistry (IHC) and western blotting. While IHC is great visualizing spatial distribution of proteins in whole organisms, it has limitations antibody availability issues related to nonspecific expression. The use blotting can circumvent expression, providing a dependable way quantify interest. Here, we present standardized, easily reproducible protocol with details on extractions planarians For complete...
Tissue homeostasis relies on the timely renewal of cells that have been damaged or surpassed their biological age. Nonetheless, underlying molecular mechanism coordinating tissue is unknown. The planarian Schmidtea mediterranea harbors a large population stem continuously divide to support restoration tissues throughout body. Here, we identify TNF Receptor Associated Factors (TRAFs) play critical roles in cellular survival during repair S. mediterranea. Disruption with RNA-interference TRAF...
Candida albicans is one of the most common fungal pathogens humans. Prior work introduced planarian Schmidtea mediterranea as a new model system to study host response infection at organismal level. In current study, we analyzed host–pathogen changes that occurred in situ during early with C. . We found transcription factor Bcr1 and its downstream adhesin Als3 are required for adhere colonize epithelial surface, adherence triggers multi-system mediated by Dectin signaling pathway. This...
Abstract Exposure to ionizing radiation can induce DNA fragmentation, leading double-strand breaks, the most toxic form of damage. Some organisms have developed mechanisms overcome adverse effects by enhancing protection and repair. However, underlying driving resistance maintain genomic integrity function remain poorly understood. Here, we provide evidence for development radiotolerance in flatworm planarian Schmidtea mediterranea . We implemented a strategy select animals capable...
ARID1A, a member of the chromatin remodeling SWI/SNF complex, is frequently lost in many cancer types, including esophageal adenocarcinoma (EAC). Here, we study impact ARID1A deficiency on anti-tumor immune response EAC. We find that EAC tumors with mutations are associated enhanced tumor-infiltrating CD8+ T cell levels. ARID1A-deficient cells exhibit heightened IFN signaling and promote recruitment cytolytic activity. Moreover, demonstrate regulates fatty acid metabolism genes EAC, showing...
Abstract Inactivation of the tumor suppressor genes TP53 and CDKN2A occurs early during gastroesophageal junction (GEJ) tumorigenesis. However, due to a paucity GEJ-specific disease models, cancer-promoting consequences inactivation at GEJ have been incompletely characterized. Here we report development first wild-type primary human organoid model, as well CRISPR-edited transformed model. CRISPR/Cas9 engineering inactivate ( TP53/CDKN2A KO ) in organoids induced morphologic dysplasia...
Background: The use of direct current electric stimulation (DCS) is an effective strategy to treat disease and enhance body functionality. Thus, treatment with DCS attractive biomedical alternative, but the molecular underpinnings remain mostly unknown. lack experimental models dissect effects from organismal levels important caveat. Here, we introduce planarian flatworm Schmidtea mediterranea as a tractable organism for in vivo studies DCS. We developed method that facilitates application...
Abstract As one of the most common malignancies, esophageal cancer has two subtypes, squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), arising from distinct cells-of-origin. However, distinguishing cell-type-specific molecular features cancer-specific characteristics been challenging. Here, we analyze whole-genome bisulfite sequencing (WGBS) data on 45 tumor nonmalignant samples both subtypes. We develop a novel sequence-aware method to identify large partially methylated domains...
Abstract Unlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify transcription factor (TF) FOXM1 as an important epigenetic regulator EAC. plays a critical role cellular proliferation and tumor growth EAC patient-derived organoids cell line models. We ERBB2 upstream expression transcriptional activity FOXM1. Unexpectedly, Gene Set Enrichment Analysis...
ABSTRACT Candida albicans is one of the most common fungal pathogens humans. Prior work introduced planarian Schmidtea mediterranea as a new model system to study host response infection at organismal level. In current study, we analyzed host-pathogen changes that occurred in situ during early with C. . We found transcription factor Bcr1 and its downstream adhesin Als3 are required for adhere colonize epithelial surface, adherence triggers multi-system mediated by Dectin signaling pathway....
Tissue homeostasis relies on the timely renewal of cells that have been damaged or surpassed their biological age. Nonetheless, underlying molecular mechanism coordinating tissue is unknown. The planarian Schmidtea mediterranea harbors a large population stem continuously divide to support restoration tissues throughout body. Here, we identify TNF Receptor Associated Factors (TRAFs) play critical roles in cellular survival during S. mediterranea. Disruption with RNA-interference TRAF...
Abstract Exposure to high levels of ionizing γ-radiation leads irreversible DNA damage and cell death. Here, we establish that exogenous application electric stimulation enables cellular plasticity reestablish stem activity in tissues damaged by radiation. We show sub-threshold direct current (DCS) rapidly restores pluripotent populations previously eliminated lethally γ-irradiated the planarian flatworm Schmidtea mediterranea . Our findings reveal DCS enhances repair, transcriptional...