We have focuses in the following areas:
Transporter regulation by intrinsically disordered domains
Transporters play vital homestatic roles that contribute to disease such as microbial drug resistance, cystic fibrosis, and dyslipidemias. Increasingly, the mechanisms behind how these roles are regulated are providing new avenues for targeting them. We study how domains that are intrinsically disordered become targets for phosphorylation or hotspots for protein-protein interactions. These types of domains provide a unique hemostat function, giving unprecedent control of function and new targets for drug development.
Metabolite regulation cancer by transporter chaperones
Successful invasion of tissue in disease – whether it is microbial or cancer – requires the coordination of extreme metabolic demands with byproducts from those processes. Tumor cells and invasive pathogens must respond to often highly acidic and hypoxic environments . Several transporter systems lie at the center of these responses and help coordinate pH tolerance, nutrient uptake, and invasion. We use structural, functional, and biochemical techniques to pick apart these systems and provide targets for development of new therapies that would literally poison cells with their own byproducts. “glutamine addiction”
Sporulation and cell wall biosyntesis in Valley Fever
Valley fever is an endemic disease in the American Southwest and Northern Arizona caused by a fungal pathogen. As part of its life cycle, Cocci makes extraordinarily hardy spores that infect the lungs and are difficult to treat. Using cryo-EM, biochemistry, and bioinformatics, we work on the steps involved in this process. We have found one, CPS1, which our collaborators have found is a vaccine target that can be used to induce immunity.