The research of faculty in the Biochemical Signaling area probes the molecular mechanisms accounting for changes in cell metabolism that mediate the physiological adaptation of living cells in response to alterations in their environment. Often these cellular responses involve sequential biochemical reactions that form signaling cascades to coordinately regulate multiple cell functions. Some of the biochemical mechanisms studied in these signaling cascades include posttranslational modifications of proteins such as phosphorylation, methylation and ubiquitination. Other mechanisms involve allosteric regulation of molecular function, including protein-protein and protein-DNA interactions. The goal of all of these studies is to understand the principles of coordinated molecular regulation at a biochemical level and to demonstrate the importance of these biochemical regulatory mechanisms in a cellular context.
Structure and mechanisms of radical and redox-active enzymes, the chemical biology of B12 trafficking, regulation of human sulfur metabolism, biochemistry of B-vitamin associated human metabolic diseases, redox communication between glial, neural, dendritic and T cells in immune and neuro-immune function.
Determining the role of molecular chaperones and disulfide catalysts in protein folding and experimental evolution of protein folding.
Control of gene expression in osteoblasts; regulation of bone formation.
Activity-dependent gene expression in skeletal muscle; Optic nerve regeneration; Retina regeneration.
Biochemical aspects of the bacterial response to heat shock.
Regulation of gene expression by proto-oncogene transcription factors; protein interactions in living cells and organisms; and nucleoprotein complex architecture.
The mechanism of post-translational modifications, such as phosphorylation and acetylation, regulating pro-apoptotic proteins in cancer cells.
Structure-activity relationship and signal transduction pathways of neuropeptides and receptors of the RFamide peptide family and their role in regulating heart rate and muscle contractions.
Microbial metabolism of energy-relevant and greenhouse gases (CO, CO2, methane) and xenobiotics (e.g., PCBs); regulation by and metabolism of CO in humans; and the roles of metal ions in biology, including the mechanisms of nickel, B12 , heme, and iron-sulfur enzymes. We use transient and steady-state kinetics, spectroscopy, and molecular biology to uncover mechanistic information.
Multinuclear NMR spectroscopy and imaging of intact biological systems, with an emphasis in experimental neuro-oncology, oxidative stress, and gene therapy.
The Saper lab studies the molecular mechanisms of how pathogenic bacteria produce and secrete a large capsule polysaccharide that enhances bacterial virulence. In particular, we focus on a regulatory tyrosine kinase and phosphatase in pathogenic E. coli. Techniques include enzyme kinetics and X-ray crystallography.
Regulation of key mediators of the mammalian stress response- Corticotropin-Releasing Hormone (CRH), CRH receptors and binding protein, and corticosteroid receptors; dysregulation of the stress response in depression and anxiety-disorders.
Molecular studies of the function of the mammalian retina, including analysis of the mechanisms controlling signal transduction and tissue-specific gene expression in the retinal pigment epithelium.
Chemical and structural biology of enzymes that covalently modify histones, transcription factors, and other nuclear proteins. Our current research focuses on elucidating the molecular mechanisms underlying the specificites of histone methyltransferases and demethylases and on developing new assays and reagents to characterize these enzymes.
Regulation and specificity of serine-threonine protein kinase structures; regulation of calcium channels and neurotransmitter secretion; function and regulation of neuronal activity; Cyclic nucleotides and phosphorylation in neuronal plasticity.
Biochemical and molecular studies of oncogenes and signaling pathways
Mechanistic structure-function relationships in ncRNAs using single molecule tools, for biomedical, bioanalytical and nanotechnological applications. The ncRNAs we study range from small RNA enzymes, such as the hammerhead, hairpin and hepatitis delta virus ribozymes with potential use in human gene therapy and relevance to human disease, to large RNA-protein complexes, such as RNA interference machinery involved in gene regulation and virus suppression.
Molecular mechanisms of protein biogenesis including protein folding, membrane trafficking, and stress response; structural biology of protein-protein interaction and molecular recognition using X-ray crystallography.