The Lippard lab studies biological interactions involving metal ions, focusing on reactions and physical and structural properties of metal complexes. Such complexes can be useful as cancer drugs and as models for the active sites of metalloproteins. Metal ions also promote key biological reactions in enzymes and metal complexes can be employed to sense biological signaling agents.
Lippard is affiliated with MIT’s Center for Cancer Research and is well known for his work on the mechanism of the anti-cancer drug cisplatin, which contains platinum and is primarily used to treat testicular cancer and ovarian cancer. His lab is currently working on designing more effective platinum anti-tumor agents.
The Lippard group also determined the structure of the component proteins of methane monooxygenase, an enzyme from aerobic bacteria that convert methane (natural gas) and oxygen to liquid methanol and water in the first step of their life process. They elucidated several key steps in the activation of oxygen and methane at a closely spaced pair of iron atoms in the enzyme. This chemistry is closely related to that used in bioremediation, processes by which microorganisms are employed to clean the environment. Examples include removal of trichloroethylene from drinking water and the cleanup of oil spills from the land. Subsequently, structures of the related hydroxylase enzymes from toluene/o-xylene monooxygenase and phenol hydroxylase, the latter in complex with its regulatory protein, were determined. Oxygenated intermediates in the catalytic cycles of the latter two enzymes have been identified.
Lippard recently developed a fluorescent sensor that monitors nitric oxide, a molecule that plays critical roles in the human body, from destroying invading microorganisms to relaying neuronal signals. The molecule had long eluded scientists because it often exists in minute concentrations and for only short periods of time. The sensor allows scientists to view nitric oxide in living cells. In related work, Lippard has also developed fluorescent and MRI sensors to detect and understand the roles of mobile zinc in the brain.