A5051180471- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- RNA modifications and cancer
- MicroRNA in disease regulation
- Cancer Research and Treatments
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Organ Transplantation Techniques and Outcomes
- Diet and metabolism studies
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- PARP inhibition in cancer therapy
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- Axon Guidance and Neuronal Signaling
- Neuroendocrine Tumor Research Advances
- Liver physiology and pathology
- Biological Research and Disease Studies
- FOXO transcription factor regulation
- Circular RNAs in diseases
- Metabolism, Diabetes, and Cancer
- Ferroptosis and cancer prognosis
University of California, Davis
2019-2025
UC Davis Comprehensive Cancer Center
2021-2025
Cornell University
2010-2023
Cold Spring Harbor Laboratory
2014-2021
Lustgarten Foundation
2014-2020
Ithaca College
2010-2011
Ludwig-Maximilians-Universität München
2010
Ruhr University Bochum
2010
Fox Chase Cancer Center
2010
National University College
2007
Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of with distinct phenotypes PDA exist. We identified a CAF subpopulation elevated expression α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic mouse human...
The miR-34 family is directly transactivated by tumor suppressor p53, which frequently mutated in human epithelial ovarian cancer (EOC). We hypothesized that expression would be decreased EOC and reconstituted might reduce cell proliferation invasion of cells.miR-34 was determined quantitative reverse transcription-PCR situ hybridization a panel 83 samples. Functional characterization accomplished reconstitution cells with synthetic pre-miR molecules followed determining changes...
Recent observations suggest that p53 mutations are responsible not only for growth of primary tumors but also their dissemination. However, mechanisms involved in p53-mediated control cell motility and invasion remain poorly understood. By using the ovarian surface epithelium culture, we show conditional inactivation or expression its mutant forms results overexpression MET receptor tyrosine kinase, a crucial regulator invasive growth. At same time, cells acquire increased MET-dependent...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common malignancy, with little improvement in patient outcomes over past decades. Recently, subtypes of pancreatic cancer different prognoses have been elaborated; however, inability to model these has precluded mechanistic investigation their origins. Here, we present a xenotransplantation PDAC which neoplasms originate from patient-derived organoids injected directly into murine ducts. Our enables distinction two main...
The miR-34 family was originally found to be a direct target of p53 and is group putative tumor suppressors. Surprisingly, mice lacking all mir-34 genes show no increase in cancer formation by 18 months age, hence placing the physiological relevance previous studies doubt. Here, we report that with prostate epithelium-specific inactivation expansion stem cell compartment develop early invasive adenocarcinomas high-grade prostatic intraepithelial neoplasia, whereas such lesions are observed...
Abstract Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within PDAC tumor microenvironment (TME), associated with poor clinical prognosis. However, despite recent advances in understanding neutrophil biology cancer, therapies targeting tumor-associated neutrophils lacking. Here, we demonstrate, using pre-clinical mouse models...
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. Altered metabolism is cancer vulnerability, several metabolic pathways have been shown to promote PDAC. However, the changes in cholesterol their role during PDAC progression remain largely unknown. Here we used organoid mouse models determine drivers of altered consequences its disruption on tumor progression. We identified sterol O-acyltransferase 1 (SOAT1) as key player sustaining mevalonate...
We recently established organoid models from normal and neoplastic murine human pancreas tissues. These organoids exhibit ductal- disease stage-specific characteristics and, after orthotopic transplantation, recapitulate the full spectrum of tumor progression. Pancreatic technology provides a novel platform for study biology discovery potential biomarkers, therapeutics, personalized medicine strategies.
Abstract Purpose: KRAS is mutated in the majority of pancreatic ductal adenocarcinoma. MAPK and PI3K-AKT are primary effector pathways, but combined PI3K inhibition has not been demonstrated to be clinically effective date. We explore resistance mechanisms uniquely employed by malignant cells. Experimental Design: evaluated expression activation receptor tyrosine kinases response MEK AKT KPC mice organoids. In addition, we sought determine therapeutic efficacy targeting pathways induced...
The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding its biological relevance limited. Here, we investigated functional role cue SEMA3A supporting PDAC progression.
Lipid rafts provide a platform for regulating cellular functions and participate in the pathogenesis of several diseases. However, role caveolin-1 this process has not been elucidated definitely neuron. Thus, study was performed to examine whether can regulate amyloid precursor protein (APP) processing neuronal cells identify molecular mechanisms involved regulation. Caveolin-1 is up-regulated all parts old rat brain, namely hippocampus, cerebral cortex elderly human cortex. Moreover,...
Abstract The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range vitro studies on model that closely recapitulates the tumor. One outstanding question biology is causes and consequences genomic heterogeneity observed disease. However, use organoids as study variations, we need first understand degree its stability within organoids. Here, used single-cell whole-genome sequencing investigate...
To date, driver genes for pancreatic cancer treatment are difficult to pursue therapeutically. Targeting mutated KRAS, the most renowned gene in cancer, is an active area of study. We discovered a named SEMA3C was highly expressed cell lines and patients with G12D mutation KRAS. High expression significantly associated decreased survival based on TCGA database. In cells, knockdown or inhibition exhibited growth/colony cycle arrest. addition, sensitized KRAS MEK1/2 cells. Overexpression...
Pancreatic ductal adenocarcinoma (PDAC) continues to be a major health problem. A ketogenic diet (KD), characterized by very low carbohydrate and high fat composition, has gained attention for its anti-tumor potential. We evaluated the effect mechanisms of feeding strict KD alone or in combination with gemcitabine autochthonous LSL-KrasG12D/+; LSL-Trp53 R172H/+; Pdx1-Cre (KPC) mouse model. For this purpose, both male female pancreatic tumor-bearing KPC mice were allocated control (CD; %kcal:...
Abstract Pancreatic cancer (PC), one of the most aggressive and life-threatening human malignancies, is known for its resistance to cytotoxic therapies. This increasingly ascribed subpopulation undifferentiated cells, as pancreatic stem cells (PCSCs), which display greater evolutionary fitness than other tumor evade effects chemotherapy. PCSCs are crucial relapse they possess ‘stem cell-like’ features that characterized by self-renewal differentiation. However, molecular mechanisms maintain...
Inherited mutation in breast cancer susceptibility gene 1 (BRCA1) is strongly associated with mammary tumors that exhibit triple-negative characteristics, are insensitive to endocrine-targeted therapies, and show basal-like properties, including aggressive phenotypes [1, 2]. It has been reported the average cumulative risk of for BRCA1 carriers by age 70 years 57% (95% confidence interval [CI]: 47%-66%) [3]. Despite high incidence characteristics BRCA1-associated cancer, few substantial...