A5072437086- Pancreatic and Hepatic Oncology Research
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Chromatin Remodeling and Cancer
- Circular RNAs in diseases
- Cancer Genomics and Diagnostics
- Phagocytosis and Immune Regulation
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Pancreatitis Pathology and Treatment
- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Cancer-related gene regulation
- RNA modifications and cancer
- MXene and MAX Phase Materials
- Mechanisms of cancer metastasis
- Signaling Pathways in Disease
- Kruppel-like factors research
- Cancer Cells and Metastasis
- Galectins and Cancer Biology
- Pancreatic function and diabetes
- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
Mayo Clinic
2016-2025
Mayo Clinic in Florida
2003-2024
Novel (United States)
2015-2024
Mayo Clinic in Arizona
2015-2024
WinnMed
2010-2024
Novelis (Canada)
2021
Cold Spring Harbor Laboratory
2014
Justus-Liebig-Universität Gießen
2014
University of Würzburg
2014
Klinikum rechts der Isar
2014
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the deregulation of hedgehog signaling pathway. The Sonic Hedgehog ligand (Shh), absent in normal pancreas, highly expressed pancreatic tumors and sufficient to induce neoplastic precursor lesions mouse models. We investigated mechanism Shh PDAC carcinogenesis genetically ablating canonical bottleneck signaling, transmembrane protein Smoothened (Smo), epithelium PDAC-susceptible mice. report that multistage development not affected...
MicroRNAs regulate pathways contributing to oncogenesis, and thus the mechanisms causing dysregulation of microRNA expression in cancer are significant interest. Mature mir-29b levels decreased malignant cells, this alteration promotes phenotype, including apoptosis resistance. However, mechanism responsible for suppression is unknown. Here, we examined mir-29 from chromosome 7q32 using cholangiocarcinoma cells as a model downregulation. Using 5' rapid amplification cDNA ends,...
Abstract Recent studies using glycogen synthase kinase-3β (GSK-3β)–deficient mouse embryonic fibroblasts suggest that GSK-3β positively regulates nuclear factor κB (NFκB)–mediated gene transcription. Because NFκB is suggested to participate in cell proliferation and survival pathways pancreatic cancer, we investigated the role of regulating these cellular processes. Herein, show cancer cells contain a pool active pharmacologic inhibition GSK-3 kinase activity small molecule inhibitors or...
KLF11 (TIEG2) is a pancreas-enriched transcription factor that has elicited significant attention because of its role as negative regulator exocrine cell growth in vitro and vivo . However, functional the endocrine pancreas remains to be established. Here, we report, for first time, our knowledge, characterization glucose-inducible insulin gene. A combination random oligonucleotide binding, EMSA, luciferase reporter, chromatin immunoprecipitation assays shows binds promoter regulates...
ATF6α, a membrane-anchored transcription factor from the endoplasmic reticulum (ER) that modulates cellular response to stress as an effector of unfolded-protein (UPR), is key player in development tumors different origin. ATF6α activation has been linked oncogenic transformation and tumor maintenance; however, mechanism(s) underlying this phenomenon remains elusive. Here, using phenotypic small interfering RNA (siRNA) screening, we identified novel role for chemoresistance defined protein...
Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance standard therapies. A more comprehensive understanding complexity PDA pathobiology, especially role microenvironment in disease progression, should pave way for therapies improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed stroma, as major driver pancreatic...
Growing evidence supports a role for the unfolded protein response (UPR) in carcinogenesis; however, precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified circadian clock PER1 mRNA as novel substrate of endoribonuclease activity UPR sensor IRE1α. Analysis mechanism shows that IRE1α decreased tumor cells without affecting gene transcription. Inhibition signaling using either siRNA-mediated silencing or dominant-negative strategy prevented decay, reduced...
Large animal models, such as the dog, are increasingly being used for studying diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge gap between commonly rodents, humans, expand translational potential of dog model, we developed a three-dimensional (3D) canine GI organoid (enteroid colonoid) system. Organoids have recently gained interest in research this model system better...
Although the biological role of KRAS is clearly established in carcinogenesis, molecular mechanisms underlying this phenomenon are not completely understood. In study, we provide evidence a novel signaling network regulated by transcription factor GLI1 mediating KRAS-induced carcinogenesis. Using pancreatic cancer (a disease with high prevalence <i>KRAS</i> mutations) as model, show that loss blocks progression preneoplastic lesions mice pancreas-specific Cre-activated oncogenic mutant...
Abstract Cancer-associated inflammation is a molecular key feature in pancreatic ductal adenocarcinoma. Oncogenic KRAS conjunction with persistent known to accelerate carcinogenesis, although the underlying mechanisms remain poorly understood. Here, we outline novel pathway whereby transcription factors NFATc1 and STAT3 cooperate epithelial cells promote KrasG12D-driven carcinogenesis. activation induced by itself accelerates inflammation-induced carcinogenesis KrasG12D mice, whereas genetic...
Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as major source therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galectin-1 (Gal1) is highly expressed in PDAC but its roles there have not been studied. Here we report functions molecular pathways Gal1 that mediate oncogenic properties this setting....
Pancreatectomy is associated with significant morbidity and unpredictable outcome, few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before operation. This study aimed define a preoperative signature panel of serum markers indicate response pancreatectomy for pancreatic cancer. Over 1000 cancer treated at two independent high-volume institutions were included in divided into three groups, including resected, locally advanced metastatic....
Understanding the molecular events controlling melanoma progression is of paramount importance for development alternative treatment options this devastating disease. Here we report a mechanism regulated by oncogenic SOX2-GLI1 transcriptional complex driving invasion through induction sialyltransferase ST3GAL1. Using in vitro and vivo studies, demonstrate that ST3GAL1 drives metastasis. Silencing enzyme suppresses significantly reduces ability aggressive cells to enter blood stream, colonize...
Abstract Proliferative chronic myelomonocytic leukemia (pCMML), an aggressive CMML subtype, is associated with dismal outcomes. RAS pathway mutations, mainly NRAS G12D , define the pCMML phenotype as demonstrated by our exome sequencing, progenitor colony assays and a Vav-Cre - Nras mouse model. Further, these mutations promote transformation to acute myeloid leukemia. Using multiomics platform biochemical molecular studies we show that in are unique gene expression profile enriched mitotic...