“One of the most rewarding experiences as a mentor of graduate students is to watch the maturation that occurs in a student's thinking and approach to solving a research problem. A very important role for an advisor in the Ph.D. training process is to know when to have a strong hand in directing a project and when to give enough independence so that the student can explore his/her own ideas. There is a great deal of pride when the balance between these two mentor roles shifts and your students develop and test their own ideas.”

Research Interests

Work in my lab focuses on the Paramyxoviruses, a diverse group of medically important RNA viruses belonging to a large family that includes measles virus, human parainfluenza virus, respiratory syncytial virus, and mumps virus. Paramyxoviruses are among the most common organisms in acute respiratory tract and systemic infections, and these ubiquitous pathogens are responsible for a high degree of morbidity and mortality worldwide.

We have three main projects involving the paramyxovirus Simian Virus 5 (SV5): 1) Control of viral gene expression and host cell antiviral responses, 2) design of novel vaccine vectors, and 3) designing viral vectors with improved selectivity for killing of tumor cells.

1. Control of viral gene expression and host cell antiviral responses. In this project, we are attempting to understand basic mechanisms for controlling virus gene expression and growth. SV5 is an unusual paramyxovirus, since it has potent mechanisms to shut down host cell responses to infection. Studies are underway to determine how SV5 prevents the death of host cells and avoids activation of cytokine synthesis.
2. Design of novel vaccine vectors. There is a growing interest in the use of paramyxoviruses such as SV5 as vaccine delivery vectors. We have shown that alterations to the SV5 gene encoding the P and V proteins results in a mutant virus that is restricted for spread in human cells, but this virus is still a potent inducer of host cell immune responses. In collaboration with the labs of Dr. Mizel, Dr. Alexander-Miller, and Dr. Lyles, we are engineering SV5 P/V mutants to express proteins from two microorganisms that have the potential for use in Bioterrorism. Our goal is to develop these SV5-based vectors and to test their ability to confer protective immunity in a mouse model system.
3. Designing viral vectors with improved selectivity for killing of tumor cells. SV5 has inherent properties that we hope to exploit to develop a new class of vectors for targeting cancer cells. We are attempting to modify the SV5 glycoproteins to produce viral vectors with enhanced ability to spread through a population of tumor cells. In addition, we are testing SV5 mutants for their ability to spread in tumor cells while retaining restricted growth in normal cells. This project is described in more detail at this link to the Susan G. Komen Foundation.

Publications

Arimilli S, Alexander-Miller MA, Parks GD. (2006). A Simian Virus 5 (SV5) P/V mutant is less cytopathic than wild type SV5 in human dendritic cells and is a more effective activator of dendritic cell maturation and function. J. Virol. 80: 3416-3427.

Pejawar SS, Parks GD, Alexander-Miller MA. (2007). Distinct pathways for signaling maturation in macrophages and dendritic cells following infection with the paramyxovirus SV5. Virol. Immunology 20:76-97.

Arimilli S, Johnson JB, Alexander-Miller MA, Parks GD. (2007). TLR-4 and -6 Agonists Reverse Apoptosis and Promote Maturation of Simian Virus 5 Infected Human Dendritic Cells Through NFkB-dependent Pathways. Virology 365: 144-156.

Dillon PJ, Parks GD. (2007). A Role for the Phosphoprotein P Subunit of the Paramyxovirus Polymerase in Limiting Induction of Host Cell Antiviral Responses. J. Virol 81: 11116-11127.

Gainey, MD, Dillon PJ, Clark KM, Manuse MJ, Parks GD. (2008). Paramyxovirus induced shut off of translation: role of P and V proteins in limiting activation of PKR. J. Virol 82:828-839.

Johnson JJ, Capraro GA, Parks GD. (2008). Differential Mechanisms of Complement-mediated Neutralization of the Closely Related Paramyxoviruses Simian Virus 5 and Mumps Virus. Virology, in press.

Capraro GA, Johnson JJ, Kock ND, Parks GD. (2008). Growth and Antibody Responses to Respiratory Tract Infection of Ferrets and Mice with WT and P/V Mutants of the Paramyxovirus Simian Virus 5. Virology, in press.

PubMed link to Parks GD