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.
Using biochemical approaches aided by biophysical tools to mechanistically dissect the responses of B cells to particulate antigens both in vivo and in vitro, with a focus on the quantitative features of viral particles and their impact on B cells.
Biochemical and structural studies of kinetochore assembly, histone chaperones, and Sestrin-mediated mTORC1 regulation.
Control of gene expression in osteoblasts; regulation of bone formation.
Identification of signaling pathways, chromatin alterations, and gene expression programs that drive central nervous system regeneration using the retina as a model system.
Biochemical aspects of the bacterial response to oxidative stress.
Protein interactions and modifications in living cells and animals; mechanisms whereby cells and animals recognize and respond to synthetic chemicals.
The mechanism of post-translational modifications, such as phosphorylation and acetylation, regulating pro-apoptotic proteins in cancer cells.
Biochemistry of the human blood clotting system; structural studies of protein-membrane complexes.
Molecular mechanisms of redox, heme, and gas signaling.
Multinuclear NMR spectroscopy and imaging of intact biological systems, with an emphasis in experimental neuro-oncology, oxidative stress, and gene therapy.
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 specificities 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