Contact info

Dr Marko Horb
Institut de Recherches Cliniques de Montréal
110, des Pins Avenue West
Montreal, QC H2W 1R7

Tel: 1-514-987-5629
Fax: 1-514-987-5780
E-mail: marko.horb@ircm.qc.ca

Link to Horb Lab webpage

Research keywords

Dr Marko Horb completed his undergraduate studies in Cellular and Structural Biology with distinction at the University of Illinois at Urbana-Champaign. In 1998 he obtained his PhD in Cellular and Developmental Biology from the State University of New York at Stony Brook, where he worked under the supervision of Dr Gerald Thomsen. His thesis dealt with the role of the T-box gene in Xenopus embryogenesis. He then moved to England to pursue his postdoctoral research in the laboratory of Prof. Jonathan M.W. Slack at the University of Bath. His postdoctoral studies focused on early endoderm patterning and pancreas development in Xenopus. In 2003 he took up a position in Montreal at the Institut de Recherches Cliniques de Montréal, where his lab is focused on elucidating the molecular signals responsible for specification of the various pancreatic lineages during embryogenesis.

Click here for PubMed listing

Current projects in the lab are focused on elucidating the molecular signals responsible for cell fate specification in the developing pancreas, with an aim towards reprogramming other cell types into endocrine beta cells. The lab uses the amphibian, Xenopus laevis, as its model organism to identify new genes involved in pancreas development. In particular the lab has shown that pancreatic transcription factors can be used to convert liver cells into functional pancreatic beta cells.

Current projects in the laboratory fall into four areas:

Transcriptional regulatory networks underlying early pancreas development. Our lab has shown that overexpression of Ptf1a and Ptf1a-VP16 in early endoderm is sufficient to promote ectopic pancreatic fates from the stomach/duodenum and liver. Through microarray analyses we are using these phenotypes to define the signaling hierarchy leading to the specification of exocrine versus endocrine cell fates. Similar experiments are being pursued with other pancreatic transcription factors, such that in the end we will be able to compare the results and obtain a global picture of how endodermal cells are specified into pancreas, how pancreas cells are specified into exocrine or endocrine lineages, and lastly how endocrine cells are specified into a single lineage.

Transdifferentiation of liver to pancreas. The ability to reprogram liver cells into pancreas for the treatment of diabetes is an alternative avenue of research. However, it is unclear if the transdifferentiation of liver to pancreas activates the same signaling pathways as those used in normal pancreas development. One of the goals in the lab is to define whether the conversion of liver to pancreas by Pdx1-VP16 or Ptf1a-VP16 activates the same pathways as in normal pancreas development.

Dorsal-ventral pancreas development. The embryonic pancreas arises from distinct dorsal and ventral pancreatic buds that are specified by different pathways. Individuals can be born without a dorsal pancreas, while abnormalities with ventral pancreas development lead to pancreas divisum and annular pancreas. In the lab we have isolated individual dorsal and ventral pancreatic buds prior to their fusion and identified functional differences between them. Current projects are focused on specific genes identified in this microarray screen.

Functional identification of new pancreatic genes. Many pancreatic genes have been identified based on their specific localization to the pancreas, but many genes may play important roles in pancreas development, which are not expressed specifically in the pancreas. To identify these genes we are using a gain-of-function approach by microinjecting various pools of mRNA into early Xenopus embryos.