My laboratory is interested in the regulatory interfaces between novel lipid-mediated signal transduction pathways and important cellular functions. A major focus of our work is the phosphatidylinositol/ phosphatidylcholine transfer proteins (PITPs), a ubiquitous but enigmatic class of proteins. Ongoing projects in the laboratory derive from a multidisciplinary approach that encompasses biochemical characterization of novel members of the metazoan PITP family, and the application of genetic, molecular and biophysical approaches to detailed structural and functional analyses of PITPs.
The laboratory breaks down into two groups: a group that studies the mechanism of function of fungal and PITPs of eukaryotic parasites (e.g. Toxoplasma), and a group that generates genetically modified mice and analyzes the function of specific PITP isoforms in the mammal with a particular focus on neural stem cell biology and embryonic development of the neocortex. Of additional interest is our recent finding that our PITP-deficient mouse lines provide unique models for study of brain inflammatory disease and defects in neural stem cell homeostasis. That latter interest is driving our present efforts in the study of autism spectrum diseases.
The yeast and Toxoplasma groups study members of the PITP family with regard to their biochemistry, structure, and biology as these relate to membrane trafficking events, cell stress responses, cell growth control, and regulation of key developmental pathways. Work in the lab is also devoted to developing small molecule inhibitors directed against target PITPs of interest, understanding how these molecules can be drugged and developing new compounds suitable for targeting the PITPs of emerging fungal pathogens – a most serious emerging global health threat.
Relevant approaches that the laboratory employs include: molecular biology, protein and lipid biochemistry, confocal and electron microscopy, mouse gene knockout technology, molecular dynamics simulations, and classical and molecular genetics.