Stephen J. Pandol, MD
Director, Basic & Translational Pancreas Research, Gastroenterology
Staff Physician, Cancer Biology & Therapeutics Research
For pancreatitis, we focus on determining the intracellular signaling (i.e. protein kinases and calcium) and organellar disorders (ER stress and mitochondrial failure) that occur during pancreatitis with the aim of identifying key ones underlying the disease process that we use to develop treatments.
For pancreatic cancer, we focus on the mechanisms of the pro-cancer functions of cells in the microenvironment of the cancer (i.e. stellate cells, macrophages, immune cells) that are involved in promoting the growth and metastasis of the cancer. Our aim is to identify specific pathways these cells use to promote the cancer with a goal of developing novel treatments for the cancer as well as prevent occurrence initially and recurrence after initial treatment.
For diabetes, we focus on how nutrients in the intestine activate gut endocrine cells (i.e. glucagon-like peptide-1 cells, cholecystokinin cells) to regulate glucose metabolism and food intake. The work involves identification of sensors and their functions on the gut endocrine cells with the aim of developing treatments for diabetes through agents that modulate these sensors.
Our research contributions include defining the molecular pathways that participate in the development of pancreatitis, as well as key molecular steps that are necessary for normal pancreatic tissue to transform into cancer.
Current investigations include:
Alcohol abuse and pancreatic necrosis; Smoking, alcohol abuse and pancreatitis; Alcohol abuse and endoplasmic reticulum dysfunction in exocrine pancreas; sXBP1: determinants of expression and role in preventing pancreatitis; Novel molecular mechanism in inflammation in macrophages and stellate cells in pancreas; Phytochemicals normalize inflammation and metabolism in pancreas; Targeted protein kinase D Inhibitor discovery and development for acute pancreatitis; Development of novel therapeutics to block IL22 function in pancreatitis; Functional MRI brain mapping in the evaluation of patients with abdominal pain
Pancreatic Cancer Projects:
Salivary biomarkers in the diagnosis of pancreatic cancer; Pathways mediating pancreatic cancer induction by alcoholic pancreatitis and smoking; Alcohol abuse, metabolic syndrome and desmoplasia in pancreatic cancer; Targeting epithelial-mesenchymal transition (EMT) pathways as a promising strategy for pancreatic cancer treatment; Targeting tumor necrosis factor receptors in pancreatic adenocarcinoma; Role of stromal HGF on stellate cells mediated pancreatic cancer; Role of Bcl-2 protein interactions in pancreatic cancer; Non-randomized clinical trial of sensory and metabolic pathway alterations following gastric surgery and caloric restriction treatments of obesity and diabetes
Non-randomized clinical trial of sensory and metabolic pathway alterations following gastric surgery and caloric restriction treatments of obesity and diabetes; Using L-cell receptors to enhance GLP-1 secretion for type 2 diabetes; Design of non-systemic drugs targeting the bitter taste receptor on enteroendocrine cells in the GI lumen
- Apte MV, Wilson JS, Lugea A, Pandol SJ: A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology, 144(6): 1210-9, 2013
- Dawson DW, Hertzer K, Moro A, Donald G, Chang HH, Go VL, Pandol SJ, Lugea A, Gukovskaya AS, Li G, Hines OJ, Rozengurt E, Eibl G: High-fat, high-calorie diet promotes early pancreatic neoplasia in the conditional KrasG12D mouse model. Cancer Prev Res (Phila), 6(10): 1064-73, 2013
- Abrol R, Edderkaoui M, Goddard 3rd, Pandol SJ: Molecular basis for the interplay of apoptosis and proliferation mediated by Bcl-xL:Bim interactions in pancreatic cancer cells. Biochem. Biophys. Res. Commun., 422(4): 596-601, 2012
- Pandol SJ, Gorelick FS, Lugea A: Environmental and genetic stressors and the unfolded protein response in exocrine pancreatic function - a hypothesis. Front Physiol, 2: 8, 2011
- Lugea A, Waldron RT, French SW, Pandol SJ: Drinking and driving pancreatitis: links between endoplasmic reticulum stress and autophagy. Autophagy, 7(7): 783-5, 2011
- Lugea A, Tischler D, Nguyen J, Gong J, Gukovsky I, French SW, Gorelick FS, Pandol SJ: Adaptive unfolded protein response attenuates alcohol-induced pancreatic damage. Gastroenterology, 140(3): 987-97, 2010