Mandy Muller Lab

Dr. Muller’s research focuses on how viruses - particularly herpesviruses like Kaposi’s sarcoma-associated herpesvirus (KSHV) - hijack host cellular machinery to promote viral replication. Her lab studies how viral infection alters gene expression in mammalian cells, with particular interest in the mechanisms that control RNA stability and viral pathogenesis.

• RNA Stability and Viral-Induced Decay: During KSHV lytic infection, the virus radically reshapes host gene expression environment by expressing SOX, a viral endoribonuclease that degrades up to 70% of the host transcriptome. This widespread RNA decay reallocates cellular resources to support viral needs. However, a subset of host mRNAs escapes SOX-mediated degradation. Our team investigates the mechanisms behind this resistance, uncovering roles for RNA structure, epitranscriptomic modifications, and 3′ end processing in protecting these transcripts. We are also interested in understanding why these transcripts escape degradation, which has led us to identify novel pro- and anti-viral host factors.
• SOX-Resistant Transcripts and KSHV Pathogenesis: KSHV is an oncogenic gammaherpesvirus responsible for cancers such as Kaposi’s Sarcoma (KS), Primary Effusion Lymphoma (PEL), and Multicentric Castleman Disease (MCD), especially in immunocompromised individuals. KS, in particular, remains a leading cancer among untreated AIDS patients. There are currently no vaccines or effective treatments for KSHV-associated cancers, which thus remain a significant threat. A long-term goal of our lab is to uncover the molecular factors that enable KSHV persistence and tumor progression. KS pathogenesis involves three interdependent processes—proliferation, angiogenesis, and inflammation - all sustained by viral and host-derived paracrine signals. Notably, many of the key paracrine factors required for KS progression are encoded by SOX-resistant transcripts. Our lab is particularly interested in how these transcripts are regulated and how they contribute to the tumor microenvironment and KSHV-associated disease.