“Our group investigates how pancreatic β-cell identity is acquired during development and impaired in response to metabolic stress.”
One of the fundamental questions in biology is how cell identity is acquired during development and modulated in response to incessantly changing environment and stress. Our group aims to understand the molecular basis for the differentiation of pancreatic β-cells in development and to identify the intricate mechanisms driving their dedifferentiation in pathological settings such as diabetes. We approach this problematic by investigating the role of microRNAs (miRNAs), a class of endogenously produced small non-coding RNAs, that recently emerged as crucial post-transcriptional regulators of gene expression in many cellular subtypes. We use a wide array of experimental methodologies including genomics, proteomics, bioinformatics and genetic manipulation in mice to identify the physiological function of miRNA gene networks in β-cells. Overall, our research program will provide crucial knowledge for the development of novel small RNA-based therapies fostering the identity and regeneration of β-cells in diabetes.
Mouse pancreatic islets revealed by indirect immunofluorescence using Insulin (green) and Glucagon (red) antibodies. Note the unique arrangement of islets with a core of Insulin-producing β-cells surrounded by Glucagon-secreting cells. Cell nucleus detected by DAPI staining (blue) (200x)
Millership SJ, Da Silva Xavier G, Choudhury AI, Bertazzo S, Chabosseau P Pedroni SM, Irvine EE, Montoya A, Faull P, Taylor WR, Kerr-Conte J, Pattou F, Ferrer J, Christian M, John RM, Latreille M, Liu M1 Rutter GA, Scott J, Withers DJ. (2018). Neuronatin regulates pancreatic β cell insulin content and secretion J Clin Invest 1, 128(8), 3369-3381 doi: 10.1172/JCI120115.
Martinez-Sanchez A, Rutter GA, Latreille M. (2017). MiRNAs in β-Cell Development, Identity, and Disease. Front Genet 11, 7, 226. doi: 10.3389/fgene.2016.00226.
Ahmed K, LaPierre MP, Gasser E, Denzler R, Yang Y, Rülicke T, Kero J, Latreille M, Stoffel M. (2017). Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility. J Clin Invest 1, 127(3), 1061-1074.
Latreille, M., Herrmanns, K., Renwick, N., Tuschl, T., Malecki, M.T., McCarthy, M.I., Owen, K.R., Rülicke, T., Stoffel, M. (2015). miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development. Journal of Molecular Medicine [Epub ahead of print] May 28.
Belgardt BF, Ahmed K, Spranger M, Latreille M, Denzler R, Kondratiuk N, von Meyenn F, Villena FN, Herrmanns K, Bosco D, Kerr-Conte J, Pattou F, Rülicke T, Stoffel M. (2015). The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes. Nature Medicine 21(6), 619-27.
Latreille M, Hausser J, Stützer I, Zhang Q, Hastoy B, Gargani S, Kerr-Conte J, Pattou F, Zavolan M, Esguerra JL, Eliasson L, Rülicke T, Rorsman P, Stoffel M. (2014). MicroRNA-7a regulates pancreatic β cell function. The Journal of Clinical Investigation 124(6), 2722–35.