A5025983460- Pancreatic and Hepatic Oncology Research
- Pancreatic function and diabetes
- Pancreatitis Pathology and Treatment
- Phagocytosis and Immune Regulation
- Metabolism, Diabetes, and Cancer
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Diabetes and associated disorders
- Cancer Treatment and Pharmacology
- TGF-β signaling in diseases
- Diet, Metabolism, and Disease
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Cells and Metastasis
- Genomic variations and chromosomal abnormalities
- Diabetes Management and Research
- Cancer, Hypoxia, and Metabolism
- Neuroendocrine Tumor Research Advances
- Mitochondrial Function and Pathology
The University of Texas Southwestern Medical Center
2010-2020
Southwestern Medical Center
2012-2020
Bilkent University
2019
A compound that binds to tubulin in an unusual way has superior antitumor efficacy and safety a distinctive impact on microtubule curvature dynamics.
Diabetes is characterized by the loss, or gradual dysfunction, of insulin-producing pancreatic beta-cells. Although beta-cells can replicate in younger adults, available diabetes therapies do not specifically target beta-cell regeneration. Novel approaches are needed to discover new therapeutics and understand contributions endocrine progenitors regeneration during islet expansion. Here, we show that regulators G protein signaling Rgs16 Rgs8 expressed progenitor cells development, then...
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related deaths in United States, and projected to be second by 2025. It has worst survival rate among all major cancers. Two pressing needs for extending life expectancy affected individuals are development new approaches identify improved therapeutics, addressed herein, identification early markers. PDA advances through a complex series intercellular physiological interactions that drive cancer progression response...
PDA is a major cause of US cancer-related deaths. Oncogenic Kras presents in 90% human PDAs. mutations occur early pre-neoplastic lesions but are insufficient to PDA. Other contributing factors disease progression include chronic pancreatitis, alterations epigenetic regulators, and tumor suppressor gene mutation. GPCRs activate heterotrimeric G-proteins that stimulate intracellular calcium oncogenic signaling, thereby promoting pancreatitis By contrast, Rgs proteins inhibit Gi/q-coupled...
Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer related deaths. Limited progress has been made in developing effective therapy for PDA. Compounding this challenge lack a systematic and robust vivo screen drug combinations. Kras mutations (e.g. G12D ) are found over 90% human PDA occur early tumor progression. Protein kinase G‐Protein Coupled Receptor (GPCR) signaling can initiate Ras activation. Regulators G‐protein Signaling (RGS) proteins coincidence detectors...
Abstract Pancreatic Ductal Adenocarcinoma (PDA) is the most lethal major cancer in USA due to lack of early diagnostics and effective treatments. Activating Kras mutations (such as KrasG12D) occur tumor progression are present about 90% PDA. Intraepithelial Neoplasms (PanIN) common initial neoplastic lesions those with activating alleles typically progress carcinoma situ metastasize. Receptor Tyrosine Kinases (RTK) G-protein Coupled Receptors (GPCR) can indirectly activate therefore...
Pancreatic insufficiency develops by about 5 weeks of age in KC (LSL‐Kras G12D ;p48 Cre ) mice that express Kras all pancreas cells. mutations (e.g. are found over 90% human PDA and an early event a multistep process leading to PDA. causes dedifferentiation acinar cells drastic reduction digestive enzymes secreted the pancreas. become malnourished but can survive one year before succumbing Ductal Adenocarcinoma (PDA). Protein kinase G‐Protein Coupled Receptor (GPCR) signaling initiate Ras...
Abstract Pancreatic ductal adenocarcinoma (PDA) is the 4th leading cause of cancer related deaths. Limited progress in developing effective therapy for PDA partially due to lack a robust vivo screen drug combinations. Kras mutations (e.g. KrasG12D) are found over 90% human and occur early tumor progression. G Protein Coupled Receptor (GPCR) protein kinase signaling can initiate Ras activation. Regulators G-protein Signaling (RGS) proteins coincidence detectors activation that feedback...
Abstract Microtubules are critical for cell proliferation, cellular invasion, migration and trafficking. As such, anti-mitotic tubulin binding agents continue to be a cornerstone of adjuvant chemotherapies across many different tumor indications. A major challenge in the development new anti-tubulin is overcome toxicities associated with targeting microtubule dynamics while maintaining high degree anti-cancer potency. Diazonamide natural product isolated from Diazona angulata, which has...
Abstract Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer related deaths. Limited progress has been made in developing effective therapy for PDA. Compounding this challenge lack a systematic and robust vivo screen drug combinations. Kras mutations (e.g. KrasG12D) are found over 90% human PDA occur early tumor progression. Protein kinase G-Protein Coupled Receptor (GPCR) signaling can initiate Ras activation. Regulators G-protein Signaling (RGS) proteins...
We seek to identify molecular markers of hormone signaling during early physiologic responses metabolic stress. Regulators G protein Signaling (RGS) proteins are feedback inhibitors ligand‐activated protein‐coupled receptors (GPCR). characterized Rgs16 gene expression in BAC transgenic GFP reporter mice pancreatic development and diabetic mice. Rg16::GFP is first expressed embryonic pancreas progenitor cells at E9 then becomes restricted endocrine later differentiation. Islet Rgs16::GFP...
Diabetes mellitus is a collection of metabolic diseases characterized by chronic hyperglycemia. Type 1 diabetes results from insulin insufficiency due to autoimmune dependent depletion producing beta cells, whereas type 2 occurs as consequence somatic cell resistance. G‐protein coupled receptors (GPCR) represent the largest non‐antibiotic drug targets and dozens them are expressed in cells. Regulator Signaling (RGS) proteins feedback modulators GPCRs. Their expression can be induced GPCR or...
Rgs16::GFP is a novel and early reporter of GPCR signaling during beta-cell expansion pancreatic ductal adenocarcinoma (PDAC). Novel approaches are needed to understand the contributions endocrine progenitors b-cell regeneration islet expansion, discover new therapeutics for diabetes that will not promote PDAC. G-protein an excellent target but well understood in pancreas development disease. Regulators (RGS) proteins can serve as biomarkers active G protein coupled receptor (GPCR)...
Abstract We have identified regulators of G protein signaling (Rgs8 and Rgs16) as a new class tumor suppressor genes in mouse model pancreatic ductal adenocarcinoma (PDA). PDA is the 3rd leading cause cancer related deaths United States. Kras mutations (e.g. KrasG12D) are associated with over 90% human an early event multistep process to PDA. can be activated by kinase G-Protein Coupled Receptor (GPCR) signaling. Rgs proteins regulate GPCR accelerating GTPase activity Gq- Gi alpha subunits....
Pancreatic Ductal Adenocarcinoma (PDA) is the most common form of pancreatic cancer driven primarily by mutations in V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (Kras) gene. Its mutation, G12D, cause KRAS to remain constitutively active. KrasG12D expressing acinar cells undergo transdifferentiation into ductal phenotype and early tumorigenic lesions called Intraepithelial Neoplasm (PanIN). Coincidentally occurring inactivating tumor suppressor genes, such as Cyclin-dependent Kinase...
P ancreatic D uctal A denocarcinoma (PDA) is the most common form of pancreatic cancer driven primarily by mutations in V ‐Ki‐Ras2 K irsten Ra t S arcoma Viral Oncogene Homolog ( Kras ) gene. Its mutation, G12D, cause KRAS to remain constitutively active. G12D expressing acinar cells undergo transdifferentiation into ductal phenotype and early tumorigenic lesions called Pan creatic I ntraepithelial N eoplasm (PanIN). Coincidentally occurring inactivating tumor suppressor genes, such as C...
Abstract Pancreatic Ductal Adenocarcinoma (PDA) is the most common form of pancreatic cancer driven primarily by mutations in V-Ki-Ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (Kras) gene. Its mutation, G12D, cause KRAS to remain constitutively active. KrasG12D expressing acinar cells undergo transdifferentiation into ductal phenotype and early tumorigenic lesions called Intraepithelial Neoplasm (PanIN). Coincidentally occurring inactivating tumor suppressor genes, such as...