Structural Studies of Dynamic Cellular Processes
University of Washington, Seattle; Postdoctoral, 1995-1999. University of California, Los Angeles; Ph.D., 1995. University of California, Davis; B.S., 1990. Burroughs Wellcome Career Award in the Biomedical Sciences 1999-2005, Phillip and Ruth Hettleman Prize for Artistic and Scholarly Achievement, 2004.
My group uses the tools of structural, molecular and chemical biology to examine dynamic cellular and systemic processes. We are currently focused on four central areas:
Nuclear Receptors in Transcriptional Control and Therapeutic Development
The nuclear receptor superfamily of proteins respond to a wide range of ligands and regulate gene expression for numerous systemic processes. The Redinbo Laboratory has studied several aspects of nuclear receptor structure-function. In published work, we have focused on the former human orphan receptors PXR, which responds to drugs, xenobiotics and endobiotics, and LRH-1, which is essential for early embryogenesis as well as adult homeostasis. In addition, we have investigated the early evolution of nuclear receptor structure by examining the 450-million year old ancestral precursors to the modern glucocorticoid receptors.
Enzymes in Chemotherapy and Chemoprotection
The Laboratory has examined both the recognition of drugs and xenobiotics by receptors like PXR, and the enzymes that break down potentially dangerous exogenous and endogenous compounds. We elucidated structures of the drug-metabolizing mammalian carboxylesterases as well as the sugar-conjugating UDP glucuronosyltransferases that facilitate drug elimination from key tissues. In addition, we are investigating enzymes essential for chemotherapeutic activation and elimination in humans, with the goal of improving drug tolerance and efficacy in cancer patients.
DNA Manipulation Machinery Structure, Function and Inhibition
Our group has a long-standing interest in the manner in which DNA and other polynucleic acids are managed and manipulated within cells. Published work in this area include several studies on human DNA topoisomerases, which are also the sole targets of the camptothecin class of potent anticancer drugs, as well as the bacterial conjugative DNA transfer process that moves antibiotic resistant genes between neighboring microbial cells. In addition, the laboratory has investigated the Werner syndrome helicase-exonuclease and the pre-mRNA processing machinery.
Bacterial Pathogenesis, Invasion and Dormancy
An emerging focus in the group is examining the mechanisms microbial pathogens use to establish and extend infections in humans. We have investigated the conjugative transfer of antibiotic resistance genes, for example, and have identified new potential approaches to targeting resistant bacteria. In addition, we are studying a range of additional microbial targets, with the long-term goal of adding new weapons to our dwindling arsenal of antibacterial drugs.