The control of gene expression is regulated in a highly organized fashion to ensure specific genes are expressed at the appropriate times and levels in response to various genetic and environmental stimuli. In eukaryotes, gene expression is controlled at multiple levels from transcription factor-mediated recruitment of the basal transcription machinery at specific gene promoters to processing and maturation of the RNA transcript. Disruption of these events in humans contributes to many pathologies including cancer, metabolic syndromes, and developmental disorders. Faculty who are investigating the regulation of gene expression are interested in numerous topics including transcriptional regulatory pathways in pro- and eukaryotes, DNA and RNA interactions with proteins, RNA processing and the functions of catalytic RNA, chromatin modification and remodeling, and three-dimensional organization of genes in the nucleus. Research employs a variety of model organisms and utilizes an array of modern techniques in biochemistry and molecular, cellular, and structural biology to elucidate the mechanisms that govern gene expression in pro- and eukaryotes.
Functions of chromatin modification enzymes in transcription regulation, cell fate determination, and cancer.
Control of gene expression in osteoblasts; regulation of bone formation.
Bacterial chromosomal structure and its effect on gene regulation, structure-function relationships in transcriptional regulators, merging experimental and computational data in protein-DNA and protein-RNA binding free energy landscapes.
Identification of signaling pathways, chromatin alterations, and gene expression programs that drive central nervous system regeneration using the retina as a model system.
Protein interactions and modifications in living cells and animals; roles of transcription factor complexes in the control of gene expression.
The mechanism of post-translational modifications, such as phosphorylation and acetylation, regulating pro-apoptotic proteins in cancer cells.
Molecular studies of the human nuclear receptor (Rev-Erb) involved in coupling metabolism to the circadian rhythm. Regulation of gene expression by heme, redox poise, and gaseous signaling molecules (CO & NO)
Molecular mechanisms that define how histone modifications and the dynamic interactions of histones with histone binding proteins encode stable and heritable patterns of gene expression.
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.
Transcriptional and post-transcriptional mechanisms that control neuronal differentiation; regulation of gene expression in the mammalian retina by microRNAs and other small RNAs.
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.
Powerful single molecule studies of mechanistic structure-dynamics-function relationships in RNAs of biomedical and bioanalytical significance. Our work ranges from small bacterial riboswitches to RNA-protein complexes involved in human disease.
Biology, mechanisms, and technological applications of bacterial CRISPR-Cas systems.