A5090281741- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Pancreatitis Pathology and Treatment
- Pancreatic function and diabetes
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Extracellular vesicles in disease
- Epigenetics and DNA Methylation
- Phagocytosis and Immune Regulation
- Ferroptosis and cancer prognosis
- Neuroblastoma Research and Treatments
- Colorectal Cancer Treatments and Studies
- HIV Research and Treatment
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Congenital gastrointestinal and neural anomalies
- MicroRNA in disease regulation
- Diabetes and associated disorders
- Gastric Cancer Management and Outcomes
- Hedgehog Signaling Pathway Studies
- Cancer, Lipids, and Metabolism
- Mycobacterium research and diagnosis
- Hepatocellular Carcinoma Treatment and Prognosis
- RNA and protein synthesis mechanisms
University of California, San Francisco
2019-2025
City College of San Francisco
2024
California Institute for Regenerative Medicine
2020
Johns Hopkins Medicine
2014-2016
Johns Hopkins University
2011-2016
The University of Texas Health Science Center at Houston
2014-2016
Johns Hopkins Hospital
2015
University of Baltimore
2014-2015
To study disease development, an inventory of organ's cell types and understanding physiologic function is paramount. Here, we performed single-cell RNA-sequencing to examine heterogeneity murine pancreatic duct cells, pancreatobiliary intrapancreatic bile cells. We describe epithelial-mesenchymal transitory axis in our three subpopulations identify osteopontin as a regulator this fate decision well human dedifferentiation. Our results further functional within by elucidating role for...
Abstract Aberrant regulation of cellular extrusion can promote invasion and metastasis. Here, we identify molecular requirements for early using a premalignant mouse model pancreatic cancer with conditional knockout p120 catenin (Ctnnd1). Mice biallelic loss progressively develop high-grade intraepithelial neoplasia (PanIN) lesions accompanied by prominent acute chronic inflammatory processes, which is mediated, in part, through NF-κB signaling. Loss the context oncogenic Kras also promotes...
The role of miRNA processing in the maintenance adult pancreatic acinar cell identity and during initiation progression neoplasia has not been studied detail. In this work, we deleted Dicer specifically cells, with or without simultaneous activation oncogenic Kras. We found that is essential for identity. Acinar cells lacking showed increased plasticity, as evidenced by loss polarity, epithelial-to-mesenchymal transition (EMT) acinar-to-ductal metaplasia (ADM). context Kras activation, ADM...
Abstract The pleiotropic roles of nSMase2-generated ceramide include regulation intracellular signaling and exosome biogenesis. Packaging specific cellular constituents, such as prion protein miRNAs involved in cancer progression, into exosomes are dependent on nSMase2. Employing the KPC mouse model pancreatic ductal adenocarcinoma (PDA), we demonstrate that nSMase2 regulates secretion vivo growth PDA cells. cell generated through accelerate independently anti-tumorigenic during progression....
Abstract The pleiotropic roles of nSMase2-generated ceramide include regulation intracellular signaling and exosome biogenesis. We investigated the effects eliminating nSMase2 on early advanced PDA, including its influence microenvironment. Employing KPC mouse model pancreatic cancer, we demonstrate that epithelial ablation reduces neoplasia promotes a PDA subtype switch from aggressive basal-like to classical. elimination prolongs survival mice, hinders vasculature development, fosters...
ABSTRACT The pleiotropic roles of nSMase2-generated ceramide include regulation intracellular signaling and exosome biogenesis. We investigated the effects eliminating nSMase2 on early advanced PDA, including its influence microenvironment. Employing KPC mouse model pancreatic cancer, we demonstrate that epithelial ablation reduces neoplasia promotes a PDA subtype switch from aggressive basal-like to classical. elimination prolongs survival mice, hinders vasculature development, fosters...
ABSTRACT Lineage tracing using genetically engineered mouse models is an essential tool for investigating cell-fate decisions of progenitor cells and biology mature cell types, with relevance to physiology disease progression. To study development, inventory organ’s types understanding physiologic function paramount. Here, we performed single-cell RNA sequencing examine heterogeneity murine pancreatic duct cells, pancreatobiliary intrapancreatic bile cells. We describe epithelial-mesenchymal...
Abstract Pancreatic cancer is the fourth most common cause of death in United States. It remains a highly lethal malignancy despite surgical and chemotherapeutic advances. In spite progress made delineating mechanisms underlying pancreatic cancer, there has been little improvement survival rates over past fifty years. Copy number analysis human invasive ductal adenocarcinoma (PDAC) revealed massively rearranged cellular karyotypes as well significant clonal complexity. Given genetic...
Abstract Pancreatic cancer is among the deadliest human malignancies ranking 4th in United States for cancer-related deaths both men and women. Due to invasive nature of pancreatic cancer, metastasis lymphatic system distant organs a major contributor death. Genetic alterations cell adhesion molecules contribute disease including developmentally related syndromes cancer. In sequencing study 24 primary tumor exomes published by Hopkins team 2008, 79% tumors had at least one mutation...
Abstract Background: The “cell of origin” for pancreatic “ductal” neoplasia remains uncertain. Selective activation Kras in the acinar cell compartment robustly generates mPanIN lesions, while similar ductal epithelial cells produces minimal change. These differences are notable considering human tumorigenesis, mutational oncogene is postulated to occur either single or small numbers cells, followed by clonal expansion and tumor initiation. We have interrogated comparative ability adult duct...
Abstract In human tumorigenesis, mutational oncogene activation is postulated to occur in either single cells or small numbers of cells, followed by clonal expansion and tumor initiation. the field pancreatic cancer research, transgenic animal models mimicking disease have contributed major advancements our understanding biology. These allowed effects oncogenic Kras (KrasG12D) be evaluated different compartments using Cre/Lox technology. When expressed under control endogenous regulatory...
Abstract By 2020, pancreatic cancer is estimated to climb from the 4th 2nd most common cause of cancer-related deaths in United States. This deadly disease has continued remain largely refractory chemotherapeutic and treatment regimens, patients often experience a heavy metastatic burden. A study combining Sleeping beauty transposon random insertion mutagenesis system with an oncogenic KrasG12D allele mice as screen identify candidate genes identified enriched adherens tight junctions...
<div>Abstract<p>Aberrant regulation of cellular extrusion can promote invasion and metastasis. Here, we identify molecular requirements for early using a premalignant mouse model pancreatic cancer with conditional knockout p120 catenin (<i>Ctnnd1</i>). Mice biallelic loss progressively develop high-grade intraepithelial neoplasia (PanIN) lesions accompanied by prominent acute chronic inflammatory processes, which is mediated, in part, through NF-κB signaling. Loss the...
<div>Abstract<p>Aberrant regulation of cellular extrusion can promote invasion and metastasis. Here, we identify molecular requirements for early using a premalignant mouse model pancreatic cancer with conditional knockout p120 catenin (<i>Ctnnd1</i>). Mice biallelic loss progressively develop high-grade intraepithelial neoplasia (PanIN) lesions accompanied by prominent acute chronic inflammatory processes, which is mediated, in part, through NF-κB signaling. Loss the...