A5090607032- Pancreatic function and diabetes
- Pancreatic and Hepatic Oncology Research
- Pancreatitis Pathology and Treatment
- RNA modifications and cancer
- Diabetes and associated disorders
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Diabetes Management and Research
- Fibroblast Growth Factor Research
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Hypoxia, and Metabolism
- FOXO transcription factor regulation
- Colorectal Cancer Treatments and Studies
- Congenital heart defects research
- Melanoma and MAPK Pathways
- Phagocytosis and Immune Regulation
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Neuroendocrine Tumor Research Advances
- Pluripotent Stem Cells Research
- Pediatric Hepatobiliary Diseases and Treatments
- Wnt/β-catenin signaling in development and cancer
- Cell Adhesion Molecules Research
- Renal and related cancers
University of Pittsburgh Medical Center
2011-2024
University of Pittsburgh
2014-2024
UPMC Hillman Cancer Center
2013-2024
Technical University of Munich
2024
Children's Hospital of Pittsburgh
2012-2024
McGowan Institute for Regenerative Medicine
2024
UConn Health
2013
Johns Hopkins University
2003-2008
Johns Hopkins Medicine
2003-2008
Johns Hopkins Hospital
2006
Pancreatic ductal adenocarcinoma (PDAC) is believed to arise through a multistep model comprised of putative precursor lesions known as pancreatic intraepithelial neoplasia (PanIN). Recent genetically engineered mouse models PDAC demonstrate comparable morphologic spectrum murine PanIN (mPanIN) lesions. The histogenesis and in both mice men remains controversial. most faithful genetic activate an oncogenic Kras(G12D) knockin allele within the pdx1- or ptf1a/p48-expression domain entire...
Notch signaling regulates cell fate decisions in a variety of adult and embryonic tissues, represents characteristic feature exocrine pancreatic cancer. In developing mouse pancreas, targeted inactivation pathway components has defined role for regulating early endocrine differentiation, but been less informative with respect to possible subsequent differentiation events. Here, we show that activated target genes actively repress completion an acinar program zebrafish pancreas. the gene Hes1...
Abstract Background β-catenin is an essential mediator of canonical Wnt signaling and a central component the cadherin-catenin epithelial adhesion complex. Dysregulation expression has been described in pancreatic neoplasia. Newly published studies have suggested that critical for normal development although these reports reached somewhat different conclusions. In addition, molecular mechanisms by which loss affects pancreas are not well understood. The goals this study then were; 1] to...
Classical cell dissociation/reaggregation experiments with embryonic tissue and cultured cells have established that cellular cohesiveness, mediated by adhesion molecules, is important in determining the organization of within organs. We employed N-CAM-deficient mice to determine whether N-CAM plays a functional role proper segregation during development islets Langerhans. In normal localization glucagon-producing α periphery pancreatic lost, resulting more randomized distribution. contrast...
Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages in pancreatic cancer microenvironment. Here, we show that neoplastic epithelium, as well a subset macrophages, expresses prolactin-receptor (PRLR). High mobility group box 1-induced prolactin expression pancreas maintained FAK1 and STAT3 phosphorylation within epithelium stroma. Gain-of-function loss-of-function experiments...
Early growth and differentiation of the pancreatic endoderm is regulated by soluble factors from mesenchyme. Previously, we demonstrated that N-cadherin-deficient mice lack a dorsal pancreas, due to critical role N-cadherin in mesenchymal cell survival. Here, show restoring cardiac circulatory function null cardiac-specific expression N-cadherin, rescues formation indicating phenotype secondary defects related cardiac/vascular function. Based on this observation, demonstrate present plasma,...
The transcription factor Snail represses E-cadherin and induces epithelial–mesenchymal transition, a process also exploited by invasive cancer cells. Aberrant Hedgehog (Hh) signaling was recently observed in variety of epithelial cancers it has been shown that the Hh target gene Gli1 expression Snail. In this study, we examined whether Sonic (SHH) are expressed neuroendocrine tumors (NETs) ileum. Using immunohistochemistry, found 22 out 37 (59%) evaluated NET samples, but not adjacent normal...
Abstract Hypoxia promotes angiogenesis, proliferation, invasion, and metastasis of pancreatic cancer. Essentially, all studies the hypoxia pathway in cancer research to date have focused on fully malignant tumors or cell lines, but potential role inducible factors (HIF) progression premalignant lesions has not been critically examined. Here, we show that HIF2α is expressed early both human a mouse model potent oncogenic stimulus, its Kras-induced neoplasia discerned. We used Ptf1aCre...
Abstract A key question in diabetes research is whether new β-cells can be derived from endogenous, nonendocrine cells. The potential for pancreatic ductal cells to convert into a highly debated issue. To date, it remains unclear what anatomical process would result duct-derived coming exist within preexisting islets. We used whole-mount technique directly visualize the network young wild-type mice, humans, and transgenic mice after partial pancreatectomy. Pancreatic networks, originating...
Abstract Insufficient functional β-cell mass causes diabetes; however, an effective cell replacement therapy for curing diabetes is currently not available. Reprogramming of acinar cells toward insulin-producing would offer abundant and autologous source cells. Our lineage tracing studies along with transcriptomic characterization demonstrate that treatment adult mice a small molecule specifically inhibits kinase activity focal adhesion results in trans-differentiation subset peri-islet into...
Abstract BACKGROUND & AIMS The exocrine pancreas has a limited regenerative capacity, but to what extent all acinar cells are involved in this process is unclear. Nevertheless, the heterogenous nature of suggests that exhibiting higher plasticity might play more prominent role regeneration. In regard, Stmn1 -expressing have been identified as potential facultative progenitor-like adult pancreas. Here, we studied Stmn1-progeny under physiological conditions, during regeneration, and...
Glucagon-producing α-cells are the second-most abundant cell type in islet. Whereas make up less than 20% of cells a mature mouse islet, they occupy much larger proportion pancreatic endocrine population during early postnatal period, time when morphological and functional maturation occurs to form adult islets. To determine whether have role islet development, diphtheria toxin-mediated α-cell ablation model was established. Rapid persistent depletion achieved by daily injection toxin for 2...
Background & AimsThere is a pressing need to develop effective preventative therapies for post–endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We showed that early PEP events are induced through the calcium-activated phosphatase calcineurin and global deletion abolishes in mice. A crucial question whether acinar cell controls initiation of vivo.MethodsWe used mouse model examined effects vivo cell-specific by either generating conditional knockout line or infusing novel...
Objective The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent basal cell type. Distinct from other epithelia with tumours, + cells reportedly do not exist in the normal pancreas. Design We evaluated human pancreas, chronic pancreatitis (CP) and PDAC. further studied depth non-cancerous tissue developed three-dimensional (3D) imaging protocol (FLIP-IT, Fluorescence Light sheet microscopic Imaging...
Prader-Willi syndrome (PWS) is a multisystem disorder caused by genetic loss of function cluster imprinted, paternally expressed genes. Neonatal failure to thrive in PWS followed childhood-onset hyperphagia and obesity among other endocrine behavioral abnormalities. typically assumed be an unknown hypothalamic-pituitary dysfunction, but the underlying pathogenesis remains unknown. A transgenic deletion mouse model (TgPWS) has severe thrive, with very low levels plasma insulin glucagon fetal...