I received my Ph.D. degree on February 1999 at the University of Barcelona, Spain, in the Department of Cell Biology under the tutoring of the late Dr. Sen Vilar. My work demonstrated that acinar cells need an intact and functional cytoskeleton for digestive enzyme secretion and that the alteration of acinar cell cytoskeleton ameliorated the severity of acute pancreatitis in rats and mice. I continued my career in the exocrine pancreas field and joined the laboratory of the professor John A. Williams, at the University of Michigan, for postdoctoral training. During that time, I was involved in the study of how the exocrine pancreas is regulated by GI hormones to synthesize digestive enzymes and/or to growth, as well as how cell/endoplasmic reticulum stress mechanisms in the exocrine pancreas can be related to acute pancreatitis. My studies in Dr. Williams's laboratory represent the first work of reference in this field. We have shown that protein synthesis and translation initiation in the exocrine pancreas is meal-stimulated, without an increase in the amount of the digestive enzymes mRNA. This indicates the importance of regulation at the translation level, rather than the transcriptional level in pancreatic acinar cells. We have also demonstrated that the branched-chain amino acid leucine can stimulate the pancreatic protein translation machinery, without involvement of CCK, cholinergic input or insulin. Additionally, we have found that acute dietary restriction of protein and amino acids inhibit pancreatic digestive enzyme synthesis (in preparation). On May 2004 I was appointed to a Research Investigator position, and since September of 2008 promoted to Research Assistant Professor. The research faculty position has allowed me to start my independent career while working under the mentorship of a senior professor. My career goal is to become a strong leader in the study of the relations between the endocrine and exocrine pancreas in physiological and pathological situations, such as diabetes, pancreatitis and pancreatic cancer. These studies will lead to a better understanding of the complex mechanisms of interaction between these two parts of the same organ as well as the inter/intra-cellular associated mechanisms between acinar and islet cells. This knowledge will have a great impact in the fields of digestion of food, nutrition and metabolism, as well as in the development of new therapies for pancreas-related diseases. Acute pancreatitis is an autodigestive process that results in acute inflammation of the pancreas characterized by edema, leukocyte infiltration, hemorrhage and cellular necrosis. The severity of the disease ranges from mild edema to severe multi-systemic organ failure with high morbidity and mortality; however, the intracellular mechanisms that trigger these processes are not fully understood. ER stress in AP has very recently captured the focus of attention. It has been speculated that disturbances in proper protein folding in other disorders such as cystic fibrosis (caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) or a1-antitrypsin deficiency can enhance the incidence of AP. Oxidative and heat-shock stresses in AP have also been studied by our group and others, but the causal role of ER stress in AP has not yet been established. The study of potential triggering events in the development of pancreatitis will contribute to design targeted therapeutic strategies for the disease. In my currently funded project from the National Pancreas Foundation (NPF), I hypothesize that the reduction on total protein synthesis seen during acute pancreatitis is mainly due to an inhibition of the synthesis of pancreatic digestive enzymes, compared to other non-secretory or structural proteins. The reduction of digestive enzyme synthesis could be a protective mechanism of the acinar cell to avoid more cell damage, triggered by endoplasmic reticulum (ER) stress response mechanisms, while the synthesis of structural or housekeeping proteins could be necessary to maintain cell viability, or be involved in the development of the disease. I also hypothesize that the phosphorylation of the ER stress transducer and translation regulator eukaryotic initiation factor (eIF) 2a is involved in such inhibition. These mechanisms could be associated with the triggering events of the disease. Another project I am working on is focused on understanding the effects of type-1 diabetes in the regulation of pancreatic digestive enzyme synthesis and secretion. This research was supported by a Pilot Project from the Michigan Diabetes Research and TrainingCenter, that has helped me to generate exocrine pancreas specific insulin receptor KO mice and to continue studies related to the effects of insulin (or the lack of it) in the exocrine pancreas physiological/pathophysiological mechanisms. I am also involved in a study to determine the role of neurohormonal stimulation and dietary protein and amino acids in the regulation of pancreatic digestive enzyme synthesis. This project was funded by a Pilot Project grant from the Michigan GI Peptide Research Center to specifically study the effects of acetylcholine stimulation through exocrine pancreas muscarinic receptors, in the regulation of digestive enzyme synthesis. Neuronal stimulation, in conjunction with hormonal (CCK and insulin) input is also being studied.