Endogenous Small Molecules in Signal Transduction.

While large-scale efforts have been applied to elucidating the functional roles of proteins and nucleic acids, our understanding of endogenous, bio-active small molecules remains primitive. We believe that interactions between proteins or nucleic acids and endogenous small molecules such as lipids or metabolites play a major and largely unexplored regulatory role in the cell.

One area of focus is sterols, lipids derived from cholesterol. Sterols influence a broad range of physiological and pathological processes, ranging from lipid metabolism and atherosclerosis to apoptosis, immunity and cancer susceptibility. In many of these cases, the specific mechanisms and molecular pathways by which sterols exert their effects on cells remain unknown. We are developing broadly applicable, next-generation methods to visualize the distribution and trafficking of sterols in cells and animals and methods to comprehensively map sites in proteins that interact with these important lipids. We strive to uncover novel regulatory mechanisms that mediate the effects of sterols
in human physiology and provide new drug targets for the large numbers of human disease states in which sterols have been implicated.