Maria Dolors Sans Gili, Ph.D. ~Research Assistant Professor of Molecular & Integrative Physiology Ph.D., Department of Cell Biology, University of Barcelona, Spain, 1999. 7737 Med Sci II (734)-764-9456 mdsansg@umich.edu

Current Research:

My field of work is the exocrine pancreas, involving the study of pancreatic physiology and pathophysiology. Since the exocrine pancreas synthesizes (and secretes) digestive enzymes in response to different stimuli it has to have a very finely regulated translational machinery. Part of my work is directed to answer how protein synthesis is regulated in the exocrine pancreas. Previous work from Dr. Williams laboratory suggested a link between translational initiation factors (IFs) and Cholecystokinin (CCK) stimulation of digestive enzymes synthesis. We studied how CCK and intracellular calcium regulate the initiation factor 2, its guanine nucleotide exchange factor (eIF2B) and the overall protein synthesis in rat pancreatic acinar cells. I have also studied the role of the calcium/calmodulin-dependent phosphatase calcineurin in regulating protein synthesis and these initiation factors.

Another focus of interest is to know the role of CCK, insulin and cholinergic input in the stimulation of pancreatic protein synthesis during normal feeding in mice, as well as to elucidate how other non-hormonal elements such as different nutrients (i.e. amino acids) can also affect this regulation in vivo. We have already studied the effect of fasting and refeeding in mice modeling meal stimulated pancreatic secretion and placing the stimulation of pancreatic protein synthesis in a physiological setting. We are also studying the pathways implicated in the trophic effect of CCK in pancreas by giving camostat (a trypsin inhibitor that stimulates the release of endogenous CCK) to mice, and in turn how are protein synthesis and the translation factors regulated by these pathways.

I am also very interested in the study of the mechanisms that can be involved in the development of acute pancreatitis (AP). We have shown that there is a reduction on the protein synthesis rates and the activation of some translation factors during the development of the caerulein model of AP in mice. The reduction on protein synthesis could be due to the activation of a stress response that could be activated by the so called endoplasmic reticulum stress (ER stress). The involvement of the ER stress in the development of AP will be one of my next projects.  
My mid-term goal is to establish my own research laboratory continuing in the world of pancreatic physiology and/or pathophysiology.

Representative Publication:

Sans MD, Tashiro M, Vogel NL, Kimball SR, D’Alecy LG and Williams JA. (2006). Leucine stimulates pancreatic translational machinery in rats and mice through mTOR independent of CCK and insulin. J Nutrition 136(7):1792-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16772439&query_hl=1&itool=pubmed_docsum

Crozier SJ, Sans MD, Guo LL, D’Alecy LG and Williams JA. (2006). Activation of the mTOR signaling pathway is required for pancreatic growth in protease inhibitor-fed mice. J Physiol 573(Pt 3):775-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16613881&query_hl=1&itool=pubmed_docsum

Kubisch CH, Sans MD, Ernst SA, Williams JA and Logsdon CD. (2006). Early activation of endoplasmic reticulum stress is associated with arginine induced acute pancreatitis. Am J Physiol Gastrointest Liver Physio 291(2):G238-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16574987&query_hl=1&itool=pubmed_docsum

Tashiro M, Dabrowski A, Guo LL, Sans MD and Williams JA. (2006). Calcineurin dependent and independent signal transduction pathways activated as part of pancreatic growth. Pancreas 32(3):314-20.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16628088&query_hl=1&itool=pubmed_docsum

Sans, M.D., Xie, Q., and Williams, J.A. (2004). Regulation of translation elongation and phosphorylation of eEF2 in rat pancreatic acini. Biochem Biophys Research Comm. 319:144-151. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15158453&query_hl=1

Sans, M.D., Lee, S-H., D’Alecy, L.G., and Williams, J.A. (2004). Feeding activates protein synthesis in mouse pancreas at the translational level without increase in mRNA. Am J Physiol-Gastrointest Liver Physiol. Apr 29 [Epub ahead of print] PMID:15117679 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15117679&query_hl=1

Sans, M.D. and Williams, J.A. (2004). Calcineurin is required for translational control of protein synthesis in rat pancreatic acini. Am J Physiol Cell Physiol. Aug;287(2):C310-9. Epub 2004 Mar 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15044154&query_hl=1

Maria Dolors Sans, Matthew J. DiMagno, Louis G. D'Alecy, and John A. Williams. Caerulein-induced acute pancreatitis inhibits protein synthesis through effects on eIF2B and eIF4F. Am J Physiol Gastrointest Liver Physiol 285: G517-G528, 2003. First published May 28, 2003.  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12773302&query_hl=1

Maria Dolors Sans and John A. Williams. Translational control of protein synthesis in pancreatic acinar cells. Int J Gastrointest Cancer. 2002;31(1-3):107-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12622421&query_hl=1

John A Williams, M.Dolors Sans, Mitsuo Tashiro, Claus Schafer, M.Julia Bragado and Andrzej Dabrowski. Cholecystokinin activates a variety of intracellular signal transduction mechanisms in rodent pancreatic acinar cells. Pharmacology & Toxicology. 2002 Dec;91(6):297-303. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12688372&query_hl=1

Maria Dolors Sans, Scot R. Kimball, and John A. Williams. Effect of CCK and intracellular calcium to regulate eIF2B and protein synthesis in rat pancreatic acinar cells. Am J Physiol (Gastrointest Liver Physiol) 2002. Feb; 282 (2):G267-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11804848&query_hl=1

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