BACKGROUND
General research focus: to identify and characterize the genetic changes that underlie cancer development and progression. In all research projects we aim to address the relevance of basic research findings for the diagnosis, prognosis and treatment of cancer patients using clinical specimens.
Research line1 .
The role of Notch proteolysis in cancer development.
The highly conserved Notch receptors transduce short-range signals that control many developmental processes and tissue self-renewal in adult vertebrates. Receptor ligand interaction results in sequential proteolytic cleavages of Notch leading to pathway activation. Mutations in Notch receptors that enhance proteolysis have been identified in human tumors. We are using i. cell culture based assays to identify the proteolytic machinery cleaving Notch receptors ii. mouse models to study the role of Notch function in normal development and cancer.
Techniques:RNA interference, transgenic and knockout mice, clonal analysis using Notch reporters in vivo, in vivo bioluminesence imaging.
Research line 2 .
The role of HIF proteins during normal physiology and cancer development.
Hypoxia (reduced oxygen tension) is one of the major hallmarks of solid tumors and predicts poor prognosis. To overcome hypoxia, tumor cells co-opt the microenvironment to provide nutrients and oxygen critical for tumor cell survival. The Hypoxia Inducible Factor (HIF) is a highly conserved bHLH transcription factor and a critical mediator in the adaptation to hypoxia by regulating glycolytic metabolism, angiogenesis and cellular survival. We are identifying the regulatory network in the hypoxic response using biochemical and genome wide approaches.
Stem cell niches are characterized by lowered oxygen tension. The intestinal stem cell niche is also regulated by Notch signaling. Hypoxia requires Notch signaling to maintain the undifferentiated state of some progenitor cells. We will investigate the interplay between Notch and hypoxia in stem cell renewal and cancer.
Techniques: gene expression analysis, microRNA, chromatin immunoprecipitation, genome-wide functional screens.
CONTACT
Research group VOOIJS
Faculty of Medicine, UMC Utrecht, Department of Pathology
Contact: Dr Marc Vooijs,
m.vooijs@umcutrecht.nl website:
www.pathologieutrecht.nl