Metabolism and disposition of xenobiotics in vivo and in vitro: isolation, identification, characterisation and quantitation of radioactive and unlabelled metabolites and DNA adducts. Enzymology of mixed-function-oxidase-dependent reactions. Toxicology of food additives, contaminants and environmental pollutants. Genotoxicity, mutagenicity and DNA binding of polycyclic aromatic hydrocarbons and nitrosubstituted arenes, and of water disinfection products.
My lab studies membrane traffic between the trans-Golgi network and endosomal organelles. This central feature of eukaryotic cell biology is important for functions of the human body; including the ability to recognize and destroy infective agents, sugar uptake in response to insulin and the proper reaction of cells to growth factors-a feature important in normal development and that is often inappropriately regulated in cancer. We have two main types of projects in the lab; characterizing protein-protein interactions important for membrane traffic and chemical genetic approach to identify compounds that regulate membrane traffic.
Dynamic control of signaling networks in living cells; Rho family and MAPK networks in motility and network plasticity; new tools to study protein activity in living cells (i.e., biosensors, protein photomanipulation, microscopy). Member of the Molecular & Cellular Biophysics Training Program and the Medicinal Chemistry Program.
We use a combination of experimental and computational methods to redesign protein-protein interactions. The potential applications for this technology include enhancing protein therapeutic and creating new tools to study signaling pathways.
We examine dynamic cellular processes using structural biology. Current projects focus on Infectious disease, particularly the spread of antibiotic resistance and host-pathogen interactions; Protein-DNA complexes involved in DNA manipulation; the Design of protein therapeutics; Nuclear receptors in transcriptional control; and Enzymes central to drug recognition and metabolism.
Bioinformatics, Cancer Biology, Cell Biology, Chemical Biology, Computational Biology, Genomics, Molecular Medicine, Neurobiology, Pharmacology, Systems Biology, Toxicology, Translational Medicine
Our laboratory applies molecular, biochemical, genetic and genomics approaches to understanding the mechanisms of environmental agent-related organ injury and carcinogenesis. Specifically, we are interested in nuclear receptor-mediated pathways in chemical carcinogenesis, oxidative DNA damage and repair, the role that alcohol and diet play in cancer, and the genetic determinants of the susceptibility to toxicant-induced liver injury. Through a combination of in vivo animal studies and experiments that utilize cellular and molecular models, we aim to better understand why certain chemicals cause cancer or organ damage in rodents and whether humans in general, or any susceptible sub-population in particular, are at risk from similar exposures.
To understand the general rules of splicing regulation, a.k.a. "splicing code", we study the splicing regulation in a systematic way. We also try to engineer molecules that can modulate splicing, and use them as drugs to treat splicing diseases.
Our vision is to address one of the great remaining and intractable problems in cellular and molecular biology -- that of determining comprehensive and quantitative structures for all cellular and viral RNAs. To this end, we are developing high-throughput RNA structure analysis technologies (called SHAPE) with the goal of making RNA secondary and tertiary structure analysis as straightforward, in principle, as DNA sequencing is today. We then use these tools to understand otherwise daunting problems that play pivotal roles in cellular function. Current projects include (i) RNA folding and protein assembly reactions central to the infectivity and pathogenesis of human viruses and (ii) assembly of large biomedically important ribonucleoprotein complexes inside living cells.
Our lab is interested in how dynamic changes in chromatin structure affect gene expression, cell lineage determination and cancer development. Currently, we are focusing on two epigenetic modifications, DNA methylation and histone methylation.
