Mailing address:
University of Colorado School of Pharmacy
Mail Stop C238
12850 E. Montview Blvd. V20-4121
Aurora, CO 80045
Office Location:
Pharmacy and Pharmaceutical Sciences Building (V20)
Fourth Floor
Room 4121
Lab Location:
Pharmacy and Pharmaceutical Sciences Building (V20)
Fourth Floor
Room 4450A(N)
Contact:
Affiliation:
- Center for Pharmaceutical Biotechnology
Training and Education:
- BS, University of Arizona (Biochemistry)
- PhD, Washington University in St. Louis (Molecular Biophysics)
Clinical / Research Interests:
My laboratory is focused on understanding the mechanisms of virus assembly in ds DNA viruses. In particular, we are interested in defining the mechanism of viral DNA packaging, which is the process by which a viral genome is either inserted into or surrounded by the viral capsid. Currently, we are studying this process in human adenovirus and bacteriophage lambda.
Adenovirus infection is common in immuno-compromised individuals, such as organ transplant recipients and HIV/AIDS patients, and can be lethal. Since DNA packaging is required for virus viability, studies of this process will provide virus-specific targets for the development of new antiviral drugs. In adenovirus, an ~ 200 bp DNA packaging sequence, located near the left end of the genome, is absolutely required for DNA packaging. Within this region are several repeated elements, called “A repeats”, which are specifically recognized by at least two virally encoded proteins, called IVa2 and L4-22kDa. While it is clear these proteins are required for DNA packaging, the mechanisms by which they are involved in this process are not clear. To begin to understand this process, we are studying the mechanism of assembly of these proteins on the packaging sequence using thermodynamic (analytical ultracentrifugation, fluorescence spectroscopy etc.) and kinetic (stopped flow) approaches.
In bacteriophage lambda, the DNA packaging reaction is catalyzed by the terminase enzyme, which couples the binding and hydrolysis of ATP to the mechanical insertion of the viral genome into the interior of the viral capsid. Recently, an in vitro system has been constructed which consists entirely of purified lambda components. This system presents an ideal opportunity to begin to define the kinetic mechanism lambda uses to catalyze viral DNA packaging.
Teaching:
Professional Program
- PHRD 3610 - Science Foundations II (Instructor)
Graduate Program
- PHSC 7350 - Protein Chemistry (Instructor)
- PHSC 7310 - Fundamentals of Pharmaceutical Sciences (Instructor)
- TXCL 7561 - Drug Metabolism (Instructor)