Graduate NIH Training in BiotechnologyTrainees
Amy Gardiner
Project Description My project involves the investigation of the role of micro (mi) RNAs in Human Papillomavirus (HPV)-associated cancers. HPVs are common papilloma (wart)-causing viruses. They are responsible for inducing a variety of cutaneous and mucosal lesions and importantly are the cause of cervical cancer. Cervical cancer is the second-highest cancer-related cause of death among women worldwide. Although a vaccine has recently been approved by the FDA, cervical cancer remains a threat for the millions of women currently infected with genital HPVs. The majority of HPV-associated carcinomas harbor integrated virus, with increased expression of the viral oncogenes E6 and E7. The viral proteins interact with a number of cellular proteins, enhancing cellular proliferation through deregulation of cell cycle control mechanisms. A novel class of gene regulators called microRNAs (miRNAs) has recently been linked to many cancers and may play a role in progression to cancer. MiRNAs are 22nt non-protein-coding RNAs that function as negative post-transcriptional gene regulators. MiRNAs hybridize to target messenger RNAs (mRNAs) and mediate translational repression or mRNA cleavage/destruction. MiRNA targets include genes involved in development, cell growth, and cell proliferation. Viruses involved in carcinogenesis have also been found to encode miRNAs. Based on this information, we postulate that HPV-16, which accounts for the majority of cervical cancers, encodes miRNAs and also affects the expression of cellular miRNAs. We are working to identify HPV-16 miRNAs and their targets. Computational analysis with the RNA-folding software mFold suggests that HPV-16 may encode miRNAs. A custom HPV-16 microarray has been designed that encompasses the HPV-16 genome in both orientations. MiRNA fractions from HPV-16 positive and HPV-16 negative cell lines will be used as probes to identify viral miRNAs. We will then identify the cellular targets through computational and experimental knock-down methods. We are also working to determine how HPV-16 affects the expression of cellular miRNAs. MiRNA microarray studies were performed in which differential expression of miRNAs was found between HPV-16 positive and HPV-16 negative cell lines. Several miRNAs that were found to be upregulated or downregulated have also been reported for other cancers such as breast, colon, and prostate. Additional microarray and expression analyses will be performed in order to characterize the role of HPV-16, particularly that of E6 and E7, in the dysregulation of miRNAs. Understanding how HPV-16 regulates viral and cellular gene expression is paramount to developing new treatments. This study will help identify new diagnostic and therapeutic targets for battling HPV infection and cervical cancer.
Courses Foundations of Biomedical Science Foundations of Biomedical Science Conference Immunology (lecture course) Experimental Virology (journal course) Scientific Ethics Research in Progress (every semester) Departmental Journal Club (weekly, every semester) Virology (transfer course) Microbial Pathogenesis (transfer course) Statistics (transfer course) TA for Medical Microbiology Fundamentals of Biochemical Engineering
Publications None
Presentations The Effect of Diabetogenic Peptides on the Conformation of the MHC Class II Molecule I-Ag7 in Type 1 Diabetes, poster presentation, 2003 Autumn Immunology Conference
22nd International Papillomavirus Conference and Clinical Workshop, 2005 Differential Expression of MicroRNAs in Human Papillomavirus (HPV)-16 Positive Cervical Carcinoma Cell Lines. 23rd International Papillomavirus Conference, 2006.
Seminars I have attended many seminars pertaining to structural biology, cell biology, biochemistry, and virology. Advisor
Saleem A. Khan Professor Molecular Genetics and Biochemistry University of Pittsburgh |
Biotechnology Program
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