Project DetailsOver the past decade, molecular geneticists have identified genes that are mutated in families with early-onset forms of AD. These genes encode presenilin 1 (PS1), presenilin 2 (PS2), and APP. G-secretase is a large macromolecular complex that consists of presenilin and several additional proteins. The focus of Dr. Zhang's project is to examine the cell biology of another protein, termed PSIP1, an evolutionary conserved molecule with no known function. Dr. Zhang has confirmed the association of PSIP1 and PS1 in stable cell lines, and has developed highly specific anti-PSIP1 antibodies to examine the subcellular distribution and trafficking of this protein. Understanding of the molecular mechanism(s) by which PSIP1 modulates g-secretase processing may offer new insights into potential targets for therapeutic intervention in AD.