BS – National University of Mexico City, Mexico (1984)
MS – National University of Mexico City, Mexico (1988)
PhD – University of Uruguay, Montevideo Uruguay (1991)
Developing more efficient methods to prevent, diagnose, and cure human diseases requires a deeper understanding of how the complex architecture of distinct organs is established, and how tissue-specific cellular diversity is generated. For about 2 decades my lab has investigated the molecular bases of hepatopancreatic cell fate specification and morphogenesis, and the effects of deregulated pancreas and liver gene expression in health and disease. Our long-term goal is to generate knowledge that helps to diagnose and treat liver and pancreatic diseases.
Members of the family of homeobox genes are key regulators of development and homeostasis in different tissues, and mutations in some of those genes have been linked to important human pathologies (e.g., cancer or diabetes). We generated several unique mouse models that we use to interrogate the function of specific homeobox genes in pancreas and liver development, or investigating the effects of altered homeobox gene activity in certain pathologic contexts. By expanding these studies using ex vivo organ explants and in silico approaches, we identified several novel gene functions that will be interrogated in follow-up in vivo and in vitro studies. Also, some of these findings will be used in protocols of directed differentiation of iPSCs and ESCs to investigate the function of the human orthologs in early endoderm development or hepatopancreatic cell fate specification, and for studying some unique aspects of their function that are difficult to approach in intact embryos.
Seth A, Ye J, Yu N, Guez F, Bedford DC, Neale GA, Cordi S, Brindle PK, Lemaigre FP, Kaestner KH, Sosa-Pineda B. Prox1 ablation in hepatic precursors causes defective hepatocyte specification and increases biliary cell commitment. Development 141(3):538-47, 2014. PMCID: PMC3899812.
Westmoreland JJ, Drosos Y, Kelly J, Ye J, Means AL, Washington MK, Sosa-Pineda B. Dynamic distribution of claudin proteins in pancreatic epithelia undergoing morphogenesis or neoplastic transformation. Dev Dyn 241:583-94, 2012. PMCID: PMC3288608.
Westmoreland JJ, Kilic G, Sartain C, Sirma S, Blain J, Rehg J, Harvey N, Sosa-Pineda B. Pancreas-specific deletion of Prox1 affects development and disrupts homeostasis of the exocrine pancreas. Gastroenterology 142(4):999-1009, 2012.
Raum JC, Hunter CS, Artner I, Henderson E, Guo M, Elghazi L, Sosa-Pineda B, Ogihara T, Mirmira RG, Sussel L, Stein R. Islet beta-cell-specific MafA transcription requires the 5'-flanking conserved region 3 control domain. Mol Cell Biol 30(17):4234-44, 2010.
Kang HS, Kim YS, ZeRuth G, Beak JY, Gerrish K, Kilic G, Sosa-Pineda B, Jensen J, Pierreux CE, Lemaigre FP, Foley J, Jetten AM. Transcription factor Glis3, a novel critical player in the regulation of pancreatic beta-cell development and insulin gene expression. Mol Cell Biol 29(24)6366-79, 2009.
Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S, Billestrup N, Madsen OD, Serup P, Heimberg H, Mansouri A. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell 138(3):449-62, 2009.
Westmoreland JJ, Wang Q, Bouzaffour M, Baker SJ, Sosa-Pineda B. PDK1 activity controls proliferation, survival and growth of developing pancreatic cells. Developmental Biology 334(1):285-298, 2009.
Wang Q, Elghazi L, Martin S, Martins I, Srinivasan S, Geng X, Sleeman M, Collombat P, Houghton J,Sosa-Pineda B. Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum. Developmental Dynamics 237(1):51-61, 2008.
Kilic G, Wang J, Sosa-Pineda B. Osteopontin is a Novel Marker of Pancreatic Ductal Tissues and of Undifferentiated Pancreatic Precursors in Mice. Developmental Dynamics 235(6):1659-1667, 2006.
Wang J, Kilic G, Aydin M, Burke Z, Oliver G, Sosa-Pineda B. Prox1 activity controls pancreas morphogenesis and participates in the production of “secondary transition” pancreatic endocrine cells. Developmental Biology 286: 182-194, 2005.
Sosa-Pineda B. The gene Pax4 is an essential regulator of pancreatic b-cell development. Mol Cells 18(3):289-294, 2004.
Prado CL, Pugh-Bernard AE, Elghazi L, Sosa-Pineda B, Sussel L. Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. PNAS 101: 4679-4684, 2004.
Wang J, Elghazi L, Parker S, Kizilocak H, Asano M, Sussel L, Sosa-Pineda B. The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic b-cell differentiation. Developmental Biology 266(1):178-189, 2004.
Sosa-Pineda B, Wigle JT, Oliver G. Hepatocyte migration during liver development requires Prox1.Nat Genet 25:254-255, 2000.
Larsson L-I, St-Onge L, Hougaard DM, Sosa-Pineda B, Gruss P. Pax4 and 6 regulate gastrointestinal endocrine cell development. Mech Dev 79:153-159, 1998.
St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P. Pax6 is required for differentiation of glucagon-producing a-cells in mouse pancreas. Nature 387:406-409, 1997.
Sosa-Pineda B, Chowdhury K, Torres M, Oliver G, Gruss P. The Pax4 gene is essential for differentiation of insulin-producing b cells in the mammalian pancreas. Nature 386:399-402, 1997.
Oliver G, Sosa-Pineda B, Geisendorf S, Spana EP, Doe CQ, Gruss P. Prox 1, a prospero-related homeobox gene expressed during mouse development. Mech Dev 44:3-16, 1993.
Last update: January 2012