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Case Western Reserve University

MOLECULAR BIOLOGY
and MICROBIOLOGY

 
 
       
 

 

Saba Valadkhan


Assistant Professor

Regulation of the host response to viral infection by long non-coding RNAs

Office Phone: 216-368-1068
Office Fax: 216.368.3055
email: saba.valadkhan@case.edu


     
 

Recent advances in understanding the transcriptional output of higher eukaryotic genome have pointed to the importance of non-protein-coding genes as both regulatory and housekeeping factors. Our laboratory is interested in the role of this class of genes in cellular function, with special emphasis on the biogenesis and function of the long non-coding RNAs (lncRNAs), a ubiquitous and highly understudied subclass. Using the host response to viral infections and HIV in particular as a model system, we have shown that the antiviral response leads to a dramatic remodeling of the cellular transcriptional output, with a significant number of both protein-coding and non-protein-coding genes showing strong changes in gene expression. Work in our laboratory and elsewhere has pointed to a crucial regulatory role for a number of Interferon-induced lncRNAs, with some lncRNAs controlling the expression of multiple protein-coding genes. Ongoing research in our lab using a combination of computational and experimental approaches aims to further understand the role of interferon-induced lncRNAs during the acute phase of viral infection.

In addition to the lncRNAs differentially expressed due to the interferon response, several interferon-independent lncRNAs are strongly induced or repressed as a result of infection by viruses such as HIV. Another line of research in the lab is focused on understanding the larger regulatory network governing both the interferon-dependent and independent virally-induced changes in gene expression, especially those regulated by lncRNAs or impacting their biogenesis. Finally, after the acute phase of infection is over, transcriptional quiescence and reactivation of the cell and the integrated proviral genome are similarly accompanied by significant changes in the expression of lncRNAs which likely play additional regulatory roles in these processes. Understanding such long-term host-virus interactions and the role of lncRNAs in these processes are additional goals of research in our lab.

Selected Publications

Gooding A.J., Zhang B., Jahanbani F.K., Gilmore H.L., Chang J.C., Valadkhan S., Schiemann W.P. 2017. The lncRNA BORG Drives Breast Cancer Metastasis and Disease Recurrence. Sci Rep. 7:12698.

Garcia-Mesa Y., Jay T.R., Checkley M.A., Luttge B., Dobrowolski C., Valadkhan S., Landreth G.E., Karn J., Alvarez-Carbonell D. 2017. Immortalization of primary microglia: a new platform to study HIV regulation in the central nervous system. J Neurovirol. 2017 Feb;23(1):47-66.

Niazi, F. and Valadkhan, S. 2016. Analysis of Long Non-coding RNAs in RNA-seq data. Book chapter in Field Guidelines for Genetic Experimental Designs in High-Throughput Sequencing. Springer, in press.

Gunawardane, LS. and Valadkhan, S. 2016. lncRNA-mediated regulation of the interferon response. Review article, Virus Research 212:127-36.

Kambara H., Gunawardane L., Zebrowski E., Kostadinova L., Jobava R., Krokowski D., Hatzoglou M., Anthony D.D. and Valadkhan S. 2015. Regulation of interferon-stimulated gene BST2 by a lncRNA transcribed from a shared bidirectional promoter. Front. Immunol. 5:676.

Kambara, H., Niazi, F., Kostadinova L., Moonka D.K., Siegel C.T., Post A.B, Carnero E., Barriocanal M., Fortes P., Anthony D.D. and Valadkhan S. 2014. Negative regulation of the interferon response by an interferon-induced long non-coding RNA. Nucleic Acid Research, 2014;42:10668-80.

Zhang, B., Gunawardane, L., Niazi, F., Jahanbani, F., Chen, X. and Valadkhan, S. 2014. A novel RNA motif mediates the strict nuclear localization of a long non-coding RNA. Mol. Cell. Biol., 34(12):2318-29.

Niazi F., Valadkhan S. 2012. Computational analysis of functional long non-coding RNAs reveals lack of peptide-coding capacity and parallels with 3'UTRs. RNA 18:825-43.