My lab studies early notochord formation and intervertebral disc development using zebrafish and mice. We are interested in understanding associated structural birth defects, intervertebral disc diseases, such as disc degeneration, and cancer. We focus on three approaches: 1) defining cis-regulatory elements of tissue-specific genes to identify their involvement in vertebrate development, in particular the notochord and intervertebral discs, as well as associated diseases, such as intervertebral disc disease, 2) using genome editing to generate disease-associated alleles to inform about future disease outcome and secondary effects, and 3) assessing the genotype-phenotype association of mutations involved in disease or phenotypes from toxicological studies.
Notochord development and associated IVD disease
We recently identified three Brachyury-bound, notochord-specific shadow enhancers that are conserved among vertebrates and could pose as important fate-sensors for nucleus pulposus-like cells, notochord organoids and IVD tissue. We are currently testing the upstream input at these enhancers controlling Brachyury expression in the notochord and how they influence notochord and intervertebral disc development. Further, knockout studies of those enhancers in mice revealed developmental tissue-specific phenotypes affecting the notochord and neural tube closure. Together with an international pool of collaborators, I extend my work into other models towards establishing mechanistic and clinical relevance of our findings. Overall, my work has generated novel insights and tools towards a better understanding of notochord development. .
RC1 North, P18-3106
12800 E. 19th Avenue
Aurora, CO 80045, USA
Office: 303-724-4867
Lab: 303-724-3016