A5066905697- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Extracellular vesicles in disease
- Dietary Effects on Health
- Esophageal Cancer Research and Treatment
- Inflammatory Bowel Disease
- Tissue Engineering and Regenerative Medicine
- Genetic factors in colorectal cancer
- Cancer, Hypoxia, and Metabolism
- Phagocytosis and Immune Regulation
- Immunodeficiency and Autoimmune Disorders
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Electrospun Nanofibers in Biomedical Applications
- Pediatric Hepatobiliary Diseases and Treatments
- Pancreatic and Hepatic Oncology Research
- Hydrogen's biological and therapeutic effects
- Whipple's Disease and Interleukins
- Gut microbiota and health
- Thermal Regulation in Medicine
- Clinical Nutrition and Gastroenterology
- Infant Nutrition and Health
- Cancer Cells and Metastasis
Children's Hospital of Philadelphia
2018-2024
Salk Institute for Biological Studies
2024
Institute for Biological Sciences
2024
University of Pennsylvania
2019-2023
Philadelphia University
2019-2023
Autophagy inhibitors are promising compounds to treat pancreatic ductal adenocarcinoma (PDA) but their efficacy in patients is unclear, highlighting a need understand mechanisms of resistance. We used novel approach uncover metabolic adaptations that bypass autophagy inhibition. Utilizing PDA cells with acquired resistance different inhibitors, we found severe depletion induces rewiring sustain TCA intermediates and nucleotides for biosynthesis. Long-term inhibition results altered pyruvate...
This work demonstrates that the RNA binding protein IGF2BP1/IMP1 alters transcript profile of colorectal cancer cell (CRC) mRNAs from extracellular vesicle (EV) pathways. IMP1 does not alter EV production or secretion in vitro vivo, but rather enters CRC cells where it may further impact cargo. Our shows has ability to shape cargo human CRC, which could serve as a diagnostic/prognostic circulating tumor biomarker.
Calorie restriction is associated with enhanced intestinal regeneration after irradiation, but the requirement of autophagy for this process not known. Our data support premise that epithelial required regenerative benefit calorie restriction. We also report luminal levels primary bile acid glycocholic are modulated by cell during direct effects on stem function.
Intestinal epithelial transit-amplifying cells are essential stem progenitors required for intestinal homeostasis, but their rapid proliferation renders them vulnerable to DNA damage from radiation and chemotherapy. Despite these cells' critical roles in homeostasis disease, few studies have described genes that cell function. We report RNA methyltransferase-like 3 (METTL3) is survival of the murine small intestine. Transit-amplifying death after METTL3 deletion was associated with crypt...
Autophagy plays roles in esophageal pathologies both benign and malignant. Here, we aim to define the role of autophagy epithelial homeostasis. We generated tamoxifen-inducible, squamous epithelial-specific Atg7 (autophagy related 7) conditional knockout mice evaluate effects on homeostasis response carcinogen 4-nitroquinoline 1-oxide (4NQO) using histologic biochemical analyses. fluorescence-activated cell sorted basal cells based fluorescence autophagic vesicle (AV)-identifying dye Cyto-ID...
Understanding how macroautophagy/autophagy contributes to tissue homeostasis is essential for understanding organismal health. The intestinal epithelium an ideal model define mechanisms that regulate because it houses well-defined populations of stem cells. Active cells (a-ISCs) are defined by their active cycling and self-renewal during homeostasis, which supports continual turnover in vivo. In vitro, this observed as long-term organoid formation capacity. A second population cells, called...
Intestinal epithelial transit amplifying cells are essential stem progenitors required for intestinal homeostasis, but their rapid proliferation renders them vulnerable to DNA damage from radiation and chemotherapy. Despite critical roles in homeostasis disease, few studies have described genes that cell function. We report the RNA methyltransferase, METTL3, is survival of murine small intestine. Transit death after METTL3 deletion was associated with crypt villus atrophy, loss absorptive...
The intestinal epithelium interfaces with a diverse milieu of luminal contents while maintaining robust digestive and barrier functions. Facultative stem cells are that survive tissue injury divide to re-establish the epithelium. Prior studies have shown autophagic state as functional marker facultative cells, but regulatory mechanisms not known. current study evaluated post-transcriptional regulation autophagy an important factor for cell regeneration. We composition, vesicle content,...
ABSTRACT Cytokines mediating epithelial and immune cell interactions modulate mucosal healing-a process that goes awry with chronic inflammation as in inflammatory bowel disease. TNFSF13 is a cytokine important for B maturation function, but roles putative contribution to disease are poorly understood. We evaluated functional consequences of novel monoallelic variant using biopsies, tissue-derived colonoids induced pluripotent stem (iPSC)-derived colon organoids. exhibited >50% reduction...
Background and rationale: The intestinal epithelium is a layer of cells that creates protective barrier separating immune from the luminal contents gut. Homeostasis maintained by actively-dividing stem (aISC). When aISCs are depleted via tissue damaging agents such as chemotherapy, irradiation, inflammation, other cell types aid in epithelial regeneration. We call these facultative because they can arise differentiated repurpose themselves unknown mechanisms. Previous work our lab showed...
Summary The intestinal epithelium exhibits a rapid and efficient regenerative response to injury. Emerging evidence supports model where plasticity of differentiated cells, particularly those in the secretory lineages, contributes epithelial regeneration upon ablation injury-sensitive stem cells. However, such facultative cell activity is rare within populations. Here we ask whether specific functional properties predict activity. We utilize vivo labeling combined with ex organoid formation...
Abstract Background & Aims Autophagy has been demonstrated to play roles in esophageal pathologies both benign and malignant. Here, we aim define the role of autophagy epithelium under homeostatic conditions. Methods We generated tamoxifen-inducible, squamous epithelial-specific Atg7 (autophagy related 7) conditional knockout mice evaluate effects on homeostasis response carcinogen 4-nitroquinoline 1-oxide (4NQO) using histological biochemical analyses. FACS sorted basal cells based upon...
Homeostatic tissue maintenance requires coordinated regulation of metabolic processes including macroautophagy/autophagy. Autophagy dysregulation underlies numerous human diseases. Our prior work revealed that the RNA binding protein IGF2BP1/IMP1 binds transcripts encoding autophagy-related proteins. Furthermore, Imp1 deletion in gastrointestinal epithelial cells mice was associated with enhanced autophagy flux and improved recovery from injury. In current study, we evaluated molecular...
Esophageal squamous epithelium comprises a basal layer of proliferative cells that differentiate in suprabasal layers before luminal desquamation, facilitating tissue renewal. Controversy exists as to whether the esophageal are functionally homogenous, with each cell having equal potential proliferate and differentiate, or heterogenous, subsets harboring differential proliferation differentiation kinetics. To examine relationship between stemness/proliferation axis autophagy cells, we...
The intestinal epithelium is a highly proliferative tissue that undergoes complete turnover in 3 to 5 days. presence of stem cells expressing the canonical Wnt target gene Lgr5, known as active (a-ISCs), are responsible for generating daughter differentiate into specialized epithelial carryout various functions intestine. nature renders it susceptible DNA damage-inducing injury, such high-dose irradiation and chemotherapy. Although a-ISCs early killed by these insults, radio-resistant...