Our research interests are on the fundamental questions of how genes get turned on and off during development and how this impacts cell fates. In particular, we are interested in how targets of the Wnt signaling pathway are activated through cis-regulatory elements.

These questions are important to pediatric health for several key reasons:

  1. Wnt signaling is one of the key signaling pathways regulating stem cell proliferation and differentiation. We aim to bring a quantitative, mechanistic understanding to how Wnt regulates its downstream targets, including those required to maintain stemness and those that trigger differentiation. This information will enable the development of more efficient protocols to differentiate stem cells and better assays to determine which cells are appropriate for transplantation as part of stem cell therapies
  2. Since the discovery of the genetic code 50 years ago, genetic research has made incredible progress in being able to identify which mutations are likely to cause disease if they occur within the protein coding regions of genes; this has helped identify the cause of many childhood genetic diseases and syndromes. However, less than 2% of the genome is protein coding genes; the rest is non-coding DNA that includes cis-regulatory elements that turn the genes on, which we are working to understand. Currently, there is no easy way to tell if mutations that occur in non-coding regions are affecting the function of cis-regulatory elements, so we cannot identify the causative mutations for a significant proportion of patients with pediatric genetic disease. Our efforts to better understand how cis-regulatory elements work will hopefully result in more patients getting a correct genetic diagnosis, helping their doctors identify better treatments and cures
  3. Our work to understand how cis-regulatory elements function could also help improve gene therapy. Many gene therapy approaches use a cis-regulatory element to activate the expression of the therapeutic gene, and by better understanding these elements, we can improve them so they only function in a particular cell type or under particular cellular conditions to reduce side effects for patients.