Abstract:

Title:

Investigating the role of membrane traffic in skin disorders

Membrane traffic is vital to the internal homeostasis of a cell and its ability to integrate with its tissue environment. Recent advances in cell biology and molecular genetics point to a role for membrane traffic in disorders that affect all major organs. With a few exceptions, however, how defective membrane traffic results in tissue-specific diseases is not well understood. The skin offers a unique opportunity to study the role and regulation of this basic cellular processes in a physiologically and clinically meaningful fashion. Chronic skin diseases such as psoriasis affect a large segment of the US population, often are associated with significant co-morbidities, and have a profound impact of an individual’s life and health care costs. The clathrin adaptor protein complex-1 (AP-1) is a central component of membrane traffic at several different organelles. Mutations in genes encoding different AP-1 subunits cause several distinct syndromes, three of which include prominent disorders of the skin. These syndromes provide a unique opportunity to answer fundamental questions about membrane traffic in a clinically meaningful setting. This project will leverage the strengths of two mentors with complementary expertise to elucidate the mechanistic basis underlying skin disorders associated with AP-1 defects.