Seminar

Seminar

Date:
15 February 2012 00:00 hrs.
Location:
Title:
Small molecule screens identify inhibitors of pigment cell development, neural crest development and melanoma growth
Speaker(s):

Dr. Grant N. Wheeler, Senior Lecturer in Cell and Developmental Biology, University of East Anglia, Norwich, UK

Host(s):

Dr. Gert-Jan Veenstra, Department of Molecular Biology, NCMLS Nijmegen

 

15-02-2012 00:00:00Europe/AmsterdamSmall molecule screens identify inhibitors of pigment cell development, neural crest development and melanoma growth Rimlsrimls@radboudumc.nl

Remarks / more information:

Grant WheelerWe have carried out forward chemical genetic screens using Xenopus laevis embryos to identify compounds disrupting pigment cell development. Phenotypes showing changes in cell migration, morphology and pigmentation were observed. Target identification of some of the compounds will be described. One compound Leflunomide, led to defects in neural crest and pigment cell development in Xenopus and zebrafish. Leflunomide is an inhibitor of Dihydroorotate Dehydrogenase, which is part of the pyrimidine synthesis pathway. Inhibiting the pool of pyrimidines in the cell leads to inhibition of transcriptional elongation. Melanoma is a tumour of transformed melanocytes, which are derived from the embryonic neural crest. When used alone or in combination with a specific inhibitor of the BRAFV600E oncogene, Leflunomide led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. We will discuss the further characterization of the molecular mechanism of Leflunomide action and the role of regulation of transcriptional elongation during neural crest development.



<< back to all events