| ESR5 - Matias DeVas, UPMC |
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Matias DeVasI am from Buenos Aires, Argentina. I have done my Master in Biological Sciences at the University of Buenos Aires, working in the laboratory of Mirtha Flawiá in the Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI). We identified and characterized a novel family of three NADPH-cytochrome P450 reductases in the protozoan parasite Trypanosoma cruzi (doi: 10.1016/j.molbiopara.2008.03.007). Moreover, we determine that members of this family (TcCPR-B and TcCPR-C) are involved in the sterol biosynthesis pathway (doi:10.1016/j.ijpara.2010.07.016). Currently, my PhD Project I am working on as part of BOLD is to address the genetic and cellular mechanisms underlying the acquisition of a multipotent pancreatic fate, the subsequent endocrine/ductal and acinar cell-lineage commitment and the generation of endocrine precursors, using the mouse as a model organism. This project is based on previous data and ongoing observations demonstrating that the transcription factor HNF1B is a key regulator of pancreas, liver and kidney organogenesis from the earliest developmental stages. In humans, heterozygous mutations in the HNF1B gene cause the multi-organ syndrome Maturity Onset Diabetes of the Young subtype 5 (MODY5) or Renal Cysts And Diabetes (RCAD), characterized by impaired glucose-stimulated insulin secretion, liver dysfunction, as well as a variety of developmental disorders including pancreas hypoplasia and abnormalities of the urogenital tract. This indicates that in addition to early developmental roles, HNF1B has additional later roles, including islet architecture and postnatal endocrine pancreas function. Through the use of Hnf1b-conditional inactivation and gain of function (cre-based inducible expression) approaches, our major objectives are to examine the involvement of HNF1B in 1. the acquisition of a pancreatic fate and the commitment of the different pancreatic cell-lineages 2. the morphogenesis of pancreatic epithelial ducts, epithelial polarization and lumen formation; the generation of endocrine precursors from pancreatic ducts during embryogenesis and in adults, under normal and regenerative conditions. 3. the regulatory circuits involved in the different processes, analyzed by ChIP, ChIP seq and RNA-Seq |
