Rho Cascades
Rho signaling is a key regulator of cytoskeleton organization, cell morphology, cell motility and cell cycle, however, despite over 30 years of study in this field there are still significant gaps in knowledge, particularly in the understanding of how Rho GTPase signal transduction pathways are regulated at the molecular level. We use structural biology, biochemical, biophysical and enzymology techniques to resolve major questions for how Rho cascades are regulated/dysregulated.
Some of our work on Rho cascades: Casanova-Sepúlveda et al., 2023; Chetty et al., 2022; Ha et al., 2022; Chetty et al., 2020; Ha et al. 2012; Hamill et al.. 2016; Ha et al., 2018; Chen and Ha et al., 2014; Davis et al., 2013; Krauthammer et al., 2012.
Cerebral vascular malformations
We study proteins whose dysregulation is responsible major cerebrovascular conditions. Cerebral Cavernous Malformations (CCM) are vascular lesions of the brain and spinal tissues and can be devastating. Three proteins are responsible for CCM (KRIT1, CCM2 and CCM3). Capillary Malformation-Arteriovenous Malformations (CM-AVM) and Vein of Galen Malformations (VOGM) are associated with mutations in RASA1, which encodes RasGAP, the first identified GTPase activating protein. Our goal in is to develop improved molecular-level understanding for how these proteins normally function, using structural analysis to guide our functional assays, to understand how signaling is disrupted in cerebrovascular disease.
Some of our work on proteins associated with cerebrovascular disease: Stiegler and Boggon, 2023; Vish et al., 2023; Stiegler et al., 2022; Chau et al., 2022; Jaber Chehayeb et al., 2019; Fisher et al., 2015; Draheim, Li et al., 2015; Fisher et al., 2015; Liu et al., 2013; Li et al., 2012; Li et al., 2010.
Pseudoenzymes and unusual adaptor interactions
Pseudoenzymes are emerging as significant mediators and regulators of signal transduction. These proteins maintain enzyme folds and topologies, but are disrupted in the conserved motifs required for enzymatic activity. We discovered, determined structures and functionally assessed multiple pseudoenzyme domains.
Some of our work on pseudoenzymes and unusual adaptor protein interactions: Stiegler and Boggon, 2020; Jaber Chehayeb et al., 2020; Stiegler and Boggon, 2018; Ha and Boggon, 2018; Stiegler and Boggon, 2018; Liu et al., 2013.
