A5070736447- Pancreatic and Hepatic Oncology Research
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Pancreatic function and diabetes
- Cellular transport and secretion
- Glycosylation and Glycoproteins Research
- Protein Kinase Regulation and GTPase Signaling
- Peptidase Inhibition and Analysis
- Metabolism, Diabetes, and Cancer
- Hair Growth and Disorders
- MicroRNA in disease regulation
- Liver physiology and pathology
- 3D Printing in Biomedical Research
- Renal and related cancers
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Bone and Dental Protein Studies
- Cell Adhesion Molecules Research
- Dermatology and Skin Diseases
- Proteoglycans and glycosaminoglycans research
- Hematopoietic Stem Cell Transplantation
- TGF-β signaling in diseases
- Neuroendocrine Tumor Research Advances
Cold Spring Harbor Laboratory
2014-2022
Lustgarten Foundation
2014-2021
Stony Brook University
2014-2021
Massachusetts General Hospital
2010-2014
Harvard University
2010-2012
The University of Texas Southwestern Medical Center
2012
University of Rochester Medical Center
2012
University of Pennsylvania
2012
Prostaglandin D 2 inhibits hair growth through its receptor, GPR44, and this pathway could serve as a new target for developing treatments male pattern baldness.
Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these contribute to disease pathogenesis is largely unknown. To study the role glycan changes in pancreatic disease, we inducibly expressed human fucosyltransferase 3 β1,3-galactosyltransferase 5 mice, reconstituting sialyl-Lewisa, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression mice resulted rapid severe pancreatitis with hyperactivation epidermal growth factor receptor...
Improved therapeutic approaches are needed for the treatment of pancreatic ductal adenocarcinoma (PDAC). As dual MEK and PI3K inhibition is presently being used in clinical trials patients with PDAC, we sought to test efficacy combined targeting these pathways PDAC using both vitro drug screens genetically engineered mouse models (GEMM).We performed high-throughput screening >500 human cancer cell lines (including 46 lines), sensitivity 50 clinically relevant compounds, including inhibitors....
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...
Abstract The TGF-β pathway is under active consideration as a cancer drug target based on its capacity to promote cell invasion and create protumorigenic microenvironment. However, the clinical application of inhibitors remains uncertain genetic studies show tumor suppressor function in pancreatic other epithelial malignancies. Here, we used genetically engineered mouse models investigate therapeutic impact global inhibition relation stage, profile, concurrent chemotherapy. We found that...
Significance For decades, KRAS interactors have been sought after as potential therapeutic targets in mutant cancers, especially pancreatic ductal adenocarcinoma (PDAC). Our proximity labeling screen with PDAC cells highlights RSK1 a notable mutant-specific interactor. Functionally, we show that mediates negative feedback on wild-type (WT) cells. Targeting oncogenic eliminates the WT RAS and role for signaling promoting adaptive resistance to ablation.
Abstract Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these contribute to disease pathogenesis is largely unknown. To study the role glycan changes in pancreatic disease, we inducibly expressed human fucosyltransferase 3 b1,3-galactosyltransferase 5 mice, reconstituting sialyl-Lewis a, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression mice resulted rapid severe pancreatitis with hyperactivation epidermal growth factor...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Although activating mutations of the KRAS GTPase are predominant dependency present in >90% PDAC patients, targeting mutants directly has been challenging PDAC. Similarly, strategies known downstream effectors have had clinical success due to feedback mechanisms, alternate pathways and toxicity normal tissues. Therefore, identifying additional functionally relevant interactions may...
Abstract Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies due to its late diagnosis and limited response treatment. Tractable model systems interrogate pathways involved in pancreatic tumorigenesis probe individual responses novel therapies are urgently needed. To that end, we established methods culture normal neoplastic duct cells as three-dimensional organoid cultures. organoids can be rapidly generated from resected tumors or fine needle biopsies, survive...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is currently the third-leading cause of cancer-related deaths in United States with no effective or targeted therapies to improve outcomes. Two defining features PDAC are dense stroma composing bulk tumor mass and mutations KRAS, primary oncogene most patients. Advances knowledge on both fronts have led promising avenues for therapeutics: recently described heterogeneity within cancer-associated fibroblast (CAF) population residing offers...
Abstract Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with 5-year survival rate less than 6%. The late diagnosis of the and poor efficacy systemic treatments are major factors for this prognosis, highlight need novel PDA models better able to predict resistance/sensitivity treatment. To fulfill need, our laboratory developed three-dimensional culture system that enables rapid growth both mouse human pancreatic organoids. Organoids can be established from healthy or neoplastic...
Abstract Circulating tumor cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While isolation and molecular analysis of these is technically challenging, they may identify cellular pathways contribute to the blood-borne dissemination cancer cells. Here, we adapted a microfluidic device for efficient capture CTCs an endogenous mouse pancreatic model subjected digital gene expression (DGE) using single molecule RNA sequencing. We...
Abstract The complexity of the tumor microenvironment (TME) is one distinguishing features pancreatic ductal adenocarcinoma (PDA) and responsible for patients’ poor response to therapies. heterogeneity cancer-associated fibroblasts (CAFs) has been correlated key stroma that contribute making PDA third-leading cause cancer-related deaths in United States. recent development FDA-approved drugs against oncogenic KRAS opened a new therapeutic avenue treatment tumors have as their driver...