Our laboratory studies the molecular mechanisms that underlie the differentiation, function and regeneration of cells in the pancreas. We investigate these mechanisms in the context of normal physiology, diabetes and cancer. In our research, we combine of variety experimental systems, including mouse genetics, a human embryonic stem cell-based in vitro differentiation platform, as well as genomic and biochemical approaches.
In recent studies, we mapped dynamic changes in the transcriptome and epigenome during the progression of pluripotent stem cells toward the pancreatic fate and discovered how chromatin remodeling events prepare developmental precursors to receive and correctly interpret organ-inductive signals. In current work, we are exploring how the cellular environment shapes the epigenome and thereby influences cellular phenotypes in the pancreas. Such knowledge will likely yield an understanding of the mechanisms underlying diseases influenced by both environmental and genetic factors, such as diabetes.
Research Focus Areas:
Developmental Biology | Genetics and Genomics | Gene Expression and Regulation | Stem Cell Biology
Taylor, B.L., Liu, F.F., Sander, M. (2013)Nkx6.1 is essential for maintaining the functional state of pancreatic beta cells. Cell Reports, 4: 1262-1275.
Xie, R., Everett, L.J., Lim, H.W., Patel, N.A., Schug, J., Kroon, E., Kelly, O.G., Wang, A., D'Amour, K.A., Robins, A.J., Won, K.J., Kaestner, K.H, Sander, M. (2013) Dynamic chromatin remodeling mediated by Polycomb proteins orchestrates pancreatic differentiation of human embryonic stem cells. Cell Stem Cell, 12:224-37.
Schaffer, A.E., Taylor, B.L., Benthuysen, J.R., Liu, J., Thorel, F., Yuan, W., Jiao, Y., Kaestner, K.H., Herrera, P.L., Magnuson, M.A., May, C.L., Sander, M. (2013) Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic beta cell identity. PLoS Genetics, 9:e1003274.
Shih, H.P., Wang, A., Sander, M. (2013) Pancreas organogenesis: From lineage determination to morphogenesis. Annual Reviews in Cell and Developmental Biology, 29: 81-105.
Kopp, J.L., von Figura, G., Mayes, E., Liu, F.F., Dubois, C.L., Morris, J.P., Pan, F.C., Akiyama, H., Wright, C.V.E., Jensen, K., Hebrok, M., Sander, M. (2012) Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell, 22, 1–14.
Shih, H.P., Kopp, J.L., Sandhu, M., Dubois, C.L., Seymour, P.A., Grapin-Botton, A., Sander, M. (2012) A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation. Development, 139:2488-99.
Seymour, P. A. , Shih, H.P., Patel, N. A., Freude, K. K., Xie, R., Lim, C.J., Sander, M. (2012) A Sox9/Fgf feed-forward loop maintains pancreatic organ identity. Development, 139: 3363-3372.