Our continuing research efforts are being driven by our interests in genetic manipulation of stem cells and whole animals for the annotation of gene function, tissue engineering, and cellular therapeutics related to cardiovascular disease. The development of the first rat embryonic stem cells from a hypertensive rat model now provides a unique foundation to establish an independent research track within the CVC in stem cell and regenerative biology. The Geurts lab will determine whether these cells are capable of supporting gene targeting technology by homologous recombination for producing genetically modified rats. In collaboration with other labs, these cells will also be directed toward cell therapeutic approaches for cardiovascular and renal disease.
The Geurts lab also focuses on developing transposable element and zinc finger nuclease (ZFN) technology for transgenesis approaches and for targeted knockout and knockin engineering in rat embryos and stem cells. Transgenesis using transposons is currently the most reproducible and efficient means for adding new genes to the rat genome. Site-specific modification of the rat genome using ZFNs to introduce specific gene alleles to correct or modulate gene function will ultimately enhance the development of novel disease models in several research areas related to our collaborative interests complex diseases such as hypertension, myocardial infarction, atherosclerosis, and renal disease.
Finally, we continue to work toward developing resources that will broadly benefit the rat genome community by participating in an effort to knock out 100 genes in rats which are related to human hypertension and renal disease. The goal is to create and initially characterize these models of genes which have been identified in human genetic studies, but for which little information exists. These animal models are then made available to the entire research community to advance our collective understanding of these complex genetic diseases.