A majority of antibiotics and drugs that we use in the clinic are derived or inspired from small organic molecules called Natural Products that are produced by living organisms such as bacteria and plants. Natural Products are at the forefront of fighting the global epidemic of antibiotic resistant pathogens, and keeping the inventory of clinically applicable pharmaceuticals stocked up. Some Natural Products are also potent human toxins and pollutants, and we need to understand how these toxins are produced to minimize our and the environmental exposure to them.
We as biochemists ask some simple questions- how and why are Natural Products produced in Nature, what we can learn from Natural Product biosynthetic processes, and how we can exploit Nature's synthetic capabilities for interesting applications?
Broadly, we are interested in questions involving (meta)genomics, biochemistry, structural and mechanistic enzymology, mass spectrometry, analytical chemistry, and how natural product chemistry dictates biology.
structural biology, protein misfolding, amyloid, glaucoma, crystallography, molecular biophysics
The Lieberman research group focuses on biophysical and structural characterization of proteins involved in misfolding disorders. One major research project in the lab has been investigations of the glaucoma-associated myocilin protein. The lab has made major strides toward detailed molecular understanding of myocilin structure, function, and disease pathogenesis. Our research has clearly demonstrated similarities between myocilin glaucoma and other protein misfolding disorders, particularly amyloid diseases. The work has led to new efforts aimed at ameliorating the misfolding phenotype using chemical biology approaches. Our second project involves the study of membrane-spanning proteolytic enzymes, which have been implicated disorders such as Alzheimer disease. Our group is tackling questions surrounding discrimination among and presentation of transmembrane substrates as well as the enzymatic details of peptide hydrolysis. In addition to the biochemical characterization of intramembrane aspartyl proteases, our group is developing new crystallographic tools to improve the likelihood of determining structures of similarly challenging membrane proteins more generally.
Development of metal specific fluorescent probes, mechanistic study of metalloprotein catalyzed reactions with unusual coordination geometries, development of protein-based, semisynthetic organometallic catalysts in aqueous solution