Research Interests

Research in our laboratory resides at the interface of chemistry and biology to understand the molecular mechanisms of metalloenzymes important for bioenergy conversion, human health and disease, or environmentally important. We use a combination of biochemical, structural, and spectroscopic techniques to investigate enzyme catalysis.

Methanogenesis. Methane, the principal component of natural gas is produced biologically by a group of microbes called methanogens. Approximately one billion tons of methane is generated every year by microbial activity and serves as a valuable source of renewable energy. Methane biogenesis is catalyzed by the nickel-containing enzyme methyl coenzyme M reductase, which contains unique amino acid modifications near the active site and we are interested in the biosynthesis of these rare post-translational modifications.

Organosulfur metabolism. The volatile organic sulfur compound dimethylsulfide (DMS) is produced in marine environments by bacterial degradation of dimethylsulfoniopropionate (DMSP). About thousands of tons of DMS is released to the atmosphere every year and it's acidic oxidation products initiate cloud nucleation. The pathways for DMSP degradation involve enzymatic cleavage to simpler sulfur compounds that are important metabolites for marine bacteria and play significant role in global sulfur and carbon cycles. We study the enzymatic degradation of bioactive marine metabolites.

Mammalian oxygen sensing pathway. The response to oxygen in mammals is regulated by hypoxia-inducible factor (HIF), a key transcription factor that senses oxygen. Under normal oxygen conditions, iron enzymes hydroxylate HIF and promote degradation. With limiting oxygen, hydroxylation of HIF is diminished thereby stimulating the transcription of hypoxia target genes. Defects in crucial oxygen sensing proteins result in defects in erythropoiesis, angiogenesis, cell proliferation, and apoptosis. Our focus is directed towards understanding various aspects of mammalian oxygen sensing at a molecular level.