Science
Information about my scientific career.
Current Work: PKR-interacting proteins and PKR’s involvement in innate signalling.
My PhD:
| Institution: | The University of Queensland, Australia |
| Department: | Diamantina Institute for Cancer, Immunology and Metabolic Medicine |
| Researchgroup: | Molecular Virology Lab |
| Date: | 02/2003 – 12/2007 |
| Project topic: | Varicella-Zoster Virus evasion of the innate interferon immune response |
| Publications: | |
| Science discipline: | Molecular virology |
| Other keywords: | High throughput screening of the VZV genome to identify genes involved in the inhibition of the Jak/STAT signalling pathway. Characterisation of potential genes from VZV that target the Jak/STAT pathway. |
My Honours:
| Institution: | University of Queensland |
| Department: | Centre for Immunology and Cancer Research |
| Researchgroup: | McMillan/Molecular Virology Group |
| Date: | 01/2002 – 12/2002 |
| Project topic: | The use of dsRNA to enhance the antiviral effetcs of IFN |
| Publications: | |
| Science discipline: | Molecular virology |
| Other keywords: | Herpes Simplex Virus, Adenovirus, Semliki Forest Virus, Sendai Virus, Vesticular Stomatitis Virus. PolyI:C enahncement of the Interferon alpha pathway. |
My Publications:
| Author(s): | Gu W, Putral LN, Irving A, McMillan NA |
| Title: | The development and future of oligonucleotide-based therapies for cervical cancer |
| Journal: | Curr Opin Mol Ther. |
| Year: | 2007 |
| Volume: | 9 |
| Issue: | 2 |
| Page: | 126-31 |
| PMID: | 17458165 |
| Article Status: | Published |
| Science discipline: | Biological sciences |
| Other keywords: | |
| Abstract: | Cervical cancer is an attractive model in which to test gene-specific therapies, because elimination of the HPV oncogenes E6 and E7 may result in cancer cell senescence. Oligonucleotide-based therapies tested over the years include antisense oligonucleotides, ribozymes and, more recently, small interfering RNA (siRNA)-based treatments. The development and use of these technologies are reviewed. siRNA-based therapies have been touted as potential treatments for cancers, genetic disorders and viral infections and have a number of advantages over antisense and ribozyme technologies. As with the older technologies, in vitro testing of siRNAs against cervical cancer has shown promising results, however, the issues that held up the clinical development of ribozymes and antisense are currently also challenging the siRNA field; these are target selection, specificity and delivery. If these issues can be overcome, a range of new and potent therapies for cervical cancer could become available. |
| Author(s): | Jiezhong Chen, Aaron Irving, Nigel McMillan, Wenyi Gu |
| Title: | Future of RNAi-based therapies for human papillomavirus-associated cervical cancer |
| Journal: | Future Virology |
| Year: | 2007 |
| Volume: | 2 |
| Issue: | 6 |
| Page: | 587-95 |
| PMID: | |
| Article Status: | Published |
| Science discipline: | Biological sciences |
| Other keywords: | |
| Abstract: | Over 99% of cervical cancers are associated with infection of high-risk type human papillomaviruses (HPV). These viruses infect epithelial cells lining the cervix and express the early viral genes E6 and E7, which are oncogenes and are primarily responsible for the transformation of the epithelial cells. The continuous expression of those genes is essential for maintenance of the cancer cell phenotype and viability. These viral genes can be silenced using oligonucleotide-based techniques, for example RNAi, antisense RNA and ribozymes. In spite of promising results in vitro and in vivo, in mice, these methods have thus far proved unsuccessful in humans, owing to the lack of an effective delivery system amongst other limitations. In this review we will discuss potential gene-silencing strategies in cervical cancer that would target both viral genes such as E6 and E7, and cellular genes that become deregulated such as E2F, p53, Akt, mTor, NF-κB or Bcl-2. By investigating these approaches we may generate an effective treatment for HPV-induced cervical cancer using gene silencing. |
| Author(s): | Clarke DT, Irving AT, Lambley EH, Payne E, McMillan NA. |
| Title: | A novel method for screening viral interferon-resistance genes. |
| Journal: | J Interferon Cytokine Res. |
| Year: | 2004 |
| Volume: | 24 |
| Issue: | 8 |
| Page: | 470-7 |
| PMID: | 15320960 |
| Article Status: | Published |
| Science discipline: | Molecular biology |
| Other keywords: | |
| Abstract: | Many viruses have evolved mechanisms to antagonize the interferon (IFN) system, targeting all the major components involved in receptor binding and signaling. Although a number of these vital proteins are homologous to cellular proteins involved in IFN downregulation (e.g., viral IFN regulatory factors [vIRFs]), many share little resemblance to known proteins. To determine the IFN-blocking properties of these proteins, functional assays are required. Here, we present a new and rapid functional screening method, based on the 2fTGH cell line, which is able to determine viral gene products that inhibit the IFN-alpha/Jak-Stat signaling pathway. Expression cloning of viral IFN-blocking genes into 2fTGH and consequent selection with IFN-alpha and 6-thioguanine result in the outgrowth of cells that are no longer responsive to IFN-alpha. We also demonstrate that selection occurs if members of the Jak-Stat signaling pathway are lost. To show the utility of our system, we have used a known suppressor of IFN signaling, the human papillomavirus (HPV) E7 gene. Expression of E7 causes the loss of ability of 2fTGH cells to respond to IFN-alpha treatment because of a functional disruption of the signaling pathway. This approach offers a new strategy for identifying novel viral genes or new functions of already described viral genes that have a role in IFN-alpha signaling inhibition. |
Teaching activity:
Tutor – undergraduate BSc. course (virology, immunology, bacterial genetics).
Supervisor – 3rd year research student.
Membership(s) in scientific society:
International Society for Interferon and Cytokine Reserach (ISICR) Professional Contact:
Monash Institute of Medical Research, CCR, 27-31 Wright St, Clayton, Vic. Aus 3168.
ResearchGate: Aaron Irving
