General Surgery Faculty

Faculty: General Surgery

Francis C. Lynn, Ph.D.

Assistant Professor
Department of Surgery
Department of Cellular and Physiological Sciences

Address:
Child & Family Research Institute
Room A4-184, 950 W 28th Ave
Vancouver BC, V5Z 4H4

Phone office:
604.875.2000 ext 5426

Fax:
604.875.2373

Summary of Research Interests

Diabetes mellitus results from dysfunction, damage or loss or of pancreatic β-cells. These cells reside in small endocrine clusters, called the islets of Langerhans, which are interspersed throughout the pancreas and secrete the hormones insulin and glucagon in response to changes in blood glucose. In order to ameliorate and eventually cure both forms of diabetes, β-cells will need to be functionally restored, regenerated, or replaced. Pancreas and islet transplantation have demonstrated the promise of β-cell replacement, but a short supply of transplantable tissue limits the applicability of these approaches in broadly curing diabetes mellitus. Our group is interested in understanding the mechanisms that regulate the formation of islet β-cells from pancreatic stem or progenitor cells during solid organ formation. We focus on the gene regulatory networks at play in the progenitor cells and how these networks change during differentiation to mature endocrine cells and in the long-term maintenance of the β-cell. We believe that a greater understanding of these genetic mechanisms and pathways will refine cell-based approaches for preventing and reversing the β-cell deterioration and loss that occurs with diabetes.

laboratory

scholarly, professional activities

Recent Publications:

SMITH, S.B., QU, H-Q., TALEB, N., KISHIMOTO, N., SCHEEL, D.W., LU, Y., PATCH, A.M., GRABS, R., WANG, J., LYNN, F.C. *, MIYATSUKA, T., MITCHELL, J., SEERKE, R., DÉSIR, J., VANDEN EJNDEN, S., ABRAMOWICZ, M., KACET, N., WEILL, J., RENARD, M-E., GENTILE, M., HANSEN, I., DEWAR, K., HATTERSLEY, A.T., WANG, R., WILSON, M.E., JOHNSON, J.D., POLYCHRONAKOS, C. & GERMAN, M.S. (2009). Endoderm Factor Rfx6 Directs Islet Formation and Insulin Production in Mice and Humans. Nature 463, 775-780.

LYNN, F.C. * (2009). Meta-regulation: microRNA regulation of glucose and lipid metabolism. Trends Endocrinol Metab 20, 452-9.

WANG, Y-C., GALLEGO, E., IEZZA, G., YUAN, X., MATLI, M.R., CHOO, S-P., ZURAEK, M.B., GOGIA, R., *LYNN, F.C., GERMAN, M.S., BERGSLAND, E.K., DONNER, D.B., WARREN, R.S., NAKAKURA, E.K. (2009). Homeodomain transcription factor Nkx2.2 functions in immature cells to control enteroendocrine differentiation and is expressed in gastrointestinal neuroendocrine tumors. Endocrine-Related Cancer 16, 267-79.

KODRA, J.T., JORGENSEN, A.S., ANDERSEN, B., BEHRENS, C., BRAND, C.L., CHRISTENSEN, I.T., GULDBRANDT, M., JEPPESEN, C.B., KNUDSEN, L.B., MADSEN, P., NISHIMURA, E., SAMS, C., SIDELMANN, U.G., PEDERSON, R.A., LYNN, F.C. * & LAU, J. (2008) Novel glucagon receptor antagonists with improved selectivity over the glucose-dependent insulinotropic polypeptide receptor. Journal of Medicinal Chemistry 51, 5387-96.

REID, J.G.*, NAGARAJA, A.K. *,LYNN, F.C. *, DRABEK, R.B., MUZNY, D.M., SHAW, C.A., WEISS, M.K., NAGHAVI, A.O., KHAN, M., ZHU, H., TENNAKOON, J., GUNARATNE, G.H., CORRY, D.B., MILLER, J., McMANUS, M.T., GERMAN, M.S., GIBBS, R.A., MATZUK, M.M., GUNARATNE, P.H. (2008). Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5'-seed/clevage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes. Genome Research 18, 1571-81. * equal contribution

LYNN, F.C. *, SANCHEZ, L., GOMIS, R., GERMAN, M.S., GASA, R. (2008). Identification of the bHLH factor Math6 as a novel component of the embryonic pancreas transcriptional network. PLoS ONE 3, e2430.

GASA, R., MREJEN, C., SANCHEZ L., YANG, K., LYNN, F.C. *, GOMIS, R., TAPSCOTT, S. & GERMAN, M.S. (2008). The Neurogenin-NeuroD1/Beta2 cascade during pancreatic development: involvement of additional NeuroD factors. Differentiation 76, 381-391.

LYNN, F.C. *, SKEWES-COX, P., KOSAKA, Y., MCMANUS, M.T., HARFE, B.D., & GERMAN, M.S. (2007). MicroRNA Expression is required for pancreatic islet cell genesis in the mouse. Diabetes 56, 2938-2945.

PITEAU, S., OLVER, A., KIM, S-J., WINTER, K., POSPISILIK, J.A., LYNN, F.C. *, MANHART, S., DEMUTH, H-U., SPECK, M., PEDERSON, R.A., MCINTOSH, C.H.S., (2007). Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycaemia in the Zucker rat. Biochem Biophys Res Commun 362, 1007-1012.

LYNN, F.C. *, SMITH, S.B.*, WILSON, M.E., YANG, K.Y., NEKREP, N., GERMAN, M.S., (2007). Sox9 coordinates a transcriptional network in pancreatic progenitor cells. Proc Natl Acad Sci USA 104, 10500-10505. * equal contribution

WILSON, M.E., YANG, K.Y., KALOUSOVA, A., LAU, J., KOSAKA, Y., LYNN, F.C. *, WANG, J., MREJEN, C., EPISKOPOU, V., CLEVERS, H.C., & GERMAN, M.S. (2005). The HMG box transcription factor SOX4 contributes to the development of the endocrine pancreas. Diabetes 54, 3402-3409.

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