The function of the pancreas and liver is essential to maintain body homeostasis, and conditions that afflict these organs can result in severe life-threatening diseases. A major aspect of our research focuses on deciphering how the complex architecture of the hepatopancreas is established during development, and how is disrupted and repaired after injury. We use genetically modified mouse models in combination with conventional and cutting-edge technologies to interrogate the function of selected transcription factors during pancreas and liver development, to identify the molecular mechanism(s) controlled by those factors, and to characterize the regulatory networks in which they participate. Our next goal is to use these and other complementary techniques (including iPSC– and ESC-derived organoids) to study key aspects of human pancreas and liver development, and apply this knowledge to the production of clinically relevant human tissues..
Our research also takes advantage of genetically modified mice to sudy mechanisms that promote neoplastic transformation and genomic instability in the pancreas, processes that help re-establishing zonation in the injured liver, and mechanisms that regulate the plasticity of mature pancreatic acinar cells.
Drosos Y, Escobar D, Chiang M-Y, Roys K, Valentine V, Valentine MB, Rehg JE, Sahai V, Begley LA, Ye J, Paul L, McKinnon PJ, Sosa-Pineda B. ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer. Sci. Rep. 7(1):11144, 2017. PMCID: PMC5593966.
Drosos Y, Neale G, Ye J, Paul L, Kuliyev E, Maitra A, Means AL, Washington MK, Rehg J, Finkelsiein DB, Sosa-Pineda B. Prox1-heterozygosis sensitizes the pancreas to oncogenic Kras-induced neoplastic transformation. Neoplasia 18(3):172-84, 2016. PMCID: PMC4796801.
Paul L, Walker EM, Drosos Y, Cyphert HA, Neale G, Stein R, South J, Grosveld G, Herrera PL, Sosa-Pineda B. Lack of Prox1 Downregulation Disrupts the Expansion and Maturation of Postnatal Murine β-cells. Diabetes. 65(3):687-98, 2016. PMCID: PMC4764148.
Seth A, Ye J, Yu N, Guez F, Bedford DC, Neale GA, Cordi S, Brindle PK, Lemaigre FP, Kaestner KH, and 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