Pharmacology and Molecular Sciences
Epstein-Barr virus and Kaposi's sarcoma herpesvirus are found in association with a variety of cancers. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to prevent, diagnose or treat them. We have become particularly interested in the unfolded protein response in activation of latent viral infection. Among the notions that we are exploring is the possibility that activation of virus-encoded enzymes will allow the targeted delivery of radiation.
Fueled by the fast-growing DNA sequence information, proteomics-the large-scale analysis of proteins-has become one of the most important disciplines to characterize protein activities and provide insight into functional network between protein molecules in a high-throughput format. More and more evidence has pointed out that proteins rarely act as single isolated species when performing their functions in vivo; they normally associate with other proteins and/or molecules as complexes and function in a network mode.
Eukaryotic cells package their genomes in the form of chromatin, which is comprised of histone proteins and DNA. Modification of chromatin by chemical marks such as methylation and acetylation affects how cellular machineries interpret the genome. The Taverna laboratory studies how histone marks contribute to an “epigenetic/histone code” that may dictate chromatin-templated functions like transcriptional activation and gene silencing, as well as how these On/Off states are inherited/ propagated.
Our work bridges from biochemical to preclinical translational studies to harness the power of glycobiology for therapeutic benefits. All cells are endowed with a diverse coat of glycans, their “glycocalyx,” which represents the face of the cell to the outside world. Glycans (complex sugar molecules) and complementary glycan-binding proteins (lectins) interact in highly specific ways to establish cell-cell interactions and regulate cell functions. Knowledge of these interactions provides opportunities to modify glycan-lectin interactions for therapeutic benefit.
Theresa A. Shapiro
The central theme of our research is antiparasitic chemotherapy. On a molecular basis, we are interested in understanding the mechanism of actionfor existing antiparasitic agents, and in identifying vulnerablemetabolic targets for much-needed, new, antiparasitic chemotherapy.Clinical studies are directed toward an evaluation, in humans, of the efficacy, pharmacokinetics, metabolism, and safety, of experimental antiparasitic drugs. The following are examples of ongoing work. 1.
J. Marie Hardwick
Our laboratory studies the basic molecular mechanisms of programmed cell death, an evolutionarily conserved process to eliminate cells. Because these pathways normally contribute to the millions of cell deaths that occur per day per individual, defects in cell death underlie the range of human disorders from cancer (insufficient cell death) to neurological diseases (excessive death). We study these processes in the nervous system, in cancer models and during virus infection using mouse models, yeast genetics and biochemical approaches.
We are interested in a molecular understanding of intracellular signal transduction pathways involved in T lymphocyte activation and apoptosis and regulation of endothelial cell proliferation. We employ a combination of techniques from protein biochemistry, molecular and cell biology and synthetic organic chemistry. Engagement of T cell receptor (TCR) with MHC-antigen complex can lead to opposite outcome, activation or death of T cells, depending on the strength or avidity of the signal.
James C. Barrow
The research group is a laboratory focused on medicinal chemistry, primarily addressing diseases of neurodevelopment such as schizophrenia. Biological activity and structure-based drug design are used to drive chemistry target selection, and we are developing synthetic methods to efficiently prepare those targets.
D. Wade Gibson
Our group is studying the structure and molecular interactions of herpesvirus proteins with the objective of understanding their role during virus replication. The long term goal of the work is to uncover new targets for antiviral drug development, and to better define events involved in virus assembly and maturation.