Assistant Professor, Microbiology-Immunology; Feinberg School of Medicine
Cancer Cell Biology
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The Gottwein lab focuses on identifying targets and functions of miRNAs encoded by the human oncogenic herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). miRNAs are ~22nt long regulatory RNAs that function to guide the recognition of binding sites in target mRNAs and thereby induce the posttranscriptional inhibition of these mRNAs. The modest amount of space miRNA precursors occupy in the encoding genome, their lack of immunogenicity and their potential as regulators of gene expression make miRNAs ideal candidates for viral effectors. While most human herpesviruses are now known to encode miRNAs, the functions of most herpesviral miRNAs remain unknown. The most common KSHV-induced disease is Kaposi’s sarcoma (KS), a complex tumor driven by KSHV-infected endothelial cells. Due to the AIDS epidemic, KS has become the most common cancer in parts of Africa. KSHV also infects B lymphocytes and can consequently cause B cell lymphomas, including primary effusion lymphoma (PEL). KSHV constitutively expresses viral miRNAs from 12 precursors, suggesting a role of these miRNAs in viral replication and pathogenesis. My lab is currently pursuing the comprehensive identification of mRNA targets of these miRNAs in primary effusion lymphoma cell lines and KSHV-infected endothelial cells. Our data suggest that, together, the KSHV miRNAs directly target hundreds of cellular mRNAs encoding proteins with roles in several different biological pathways. Our goal is to use this knowledge to characterize the most important functions of the KSHV miRNAs.