Michael C. Wiener, PhD
Structural biology of membrane proteins (Cisplatin uptake)
Membrane protein structural biology is a frontier area of modern biomedical science, and a number of significant structures of channels, transporters and receptors have been determined recently. However, only a tiny fraction of membrane proteins have had their structures solved, and there are no structures of recombinant eukaryotic membrane proteins. The Wiener lab is directing research towards the structural biology of human membrane proteins of basic and applied biomedical interest. Two projects of direct relevance to cancer biology are mentioned below. Each is currently funded by a two-year NIH R21 grant.
Copper is directly involved in many human physiological processes and protects cells from potentially mutagenic DNA damage by free radicals. Copper deficiency has been implicated in anemia, cardiovascular abnormalities, neurodegeneration, tumorigenesis, angiogenesis, and neutropenia (a common toxicological consequence of chemotherapy). The integral membrane protein Ctr1 is responsible for the cellular uptake of copper. Unexpectedly, hCtr1 also is responsible for uptake of platinum cytotoxic anticancer drugs such as cisplatin, and thus presents a possible target for the design of related drugs with improved uptake properties.