Lee Lab

 

 

 

 

 

 

Our lab looks at the design of membrane transport proteins—how they use their architecture to take advantage of selective transport and how we can use this selective transport for therapeutic potential in humans.

About Membrane Transport Proteins

Membrane transport proteins can selectively recognize a variety of substrates of differing sizes and physicochemical properties for cellular transport, thus they are responsible for the movement of key molecules and the transfer of information across cell membranes—events central to many important physiological processes.

Our Techniques

We use a variety of structural and biophysical methods including X-ray crystallography, cryo-EM, radiolabeled ligand flux assay, electrophysiology, and isothermal titration calorimetry to study three transport processes: ions (calcium), nucleosides (nucleosides and nucleoside anticancer drugs), and lipids (lipid-linked oligosaccharides). All are associated with various physiological and pathophysiological processes such as somatosensation, pain, cancer, and bacterial infection.

Areas of Research Focus

Calcium Permeation
In the Lee lab, we focus on elucidating the molecular mechanisms of two sub-families of Ca2+ permeable ion channels: Transient Receptor Potential (TRP) channels and organellar Ca2+ channels. Ion channels are a large superfamily of integral membrane proteins that enable various species of ions to traverse cell membranes.

Nucleoside Transport
Our lab is interested in a detailed mechanistic understanding of cellular nucleoside and nucleoside-derived drug transport mediated by concentrative nucleoside transport proteins (CNTs). Nucleoside transport is vital to a wide variety of physiological processes including metabolism, cellular signaling, and nucleoside-based drug uptake and excretion.

Lipid transport
We want to understand the mechanism of lipid transport by membrane transport proteins and how inhibitors block this transport to exert their cellular effects. The biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and N-linked glycans) necessitates the membrane transport of polysaccharide precursors from their cytoplasmic site of synthesis to their site of assembly outside the cytoplasm. To accomplish this task, cells utilize a translocase to attach the precursor to a carrier lipid, and a flippase to transport the lipid-linked precursor across the membrane.