The lab is focused in the study of ciliary biology, and more specifically how this organelle and the proteins that compose it modulate cell fate decisions such as whether to proliferate or differentiate. Ciliary dysfunction underlies the pathogenesis of a broad group of human disorders collectively known as ciliopathies that are characterized by a number of phenotypes including retinal degeneration, cystic kidney disease, obesity, and diabetes. One example of a ciliopathy, and the model we study in the lab, is Bardet-Biedl syndrome (BBS), a genetically heterogeneous disorder for which 16 genes have been cloned to date.
The BBS proteins tested to date localize to centrosomes, basal bodies and in some cases the ciliary compartment and defects in this group of proteins can result in both structural and functional ciliary defects such as the misregulation of the Wnt signaling pathway. In the context of the Wnt signaling cascade, the BBS proteins appear to modulate the balance between the canonical/β-catenin dependent and non-canonical or planar cell polarity (PCP) pathways. However, despite the availability of 16 BBS proteins, their exact role in ciliary formation/function is still poorly understood. Consequently, BBS represents a powerful model to study the biology of cilia and their role in signal transduction to modulate cell fate. In the lab we are conducting both in vitro and in vivo studies designed to gain insight into the cellular function of the BBS and other cilia-associated proteins, both in the context of the cilium as well as potentially outside of it.
Additionally, BBS is an oligogenic disorder whereby mutations at more than one locus collaborate to modulate disease outcome and thus it also represents an opportunity to understand oligogenic inheritance at a cellular and molecular level.