Complex transcriptional control is a conserved feature of both eukaryotes and the viruses that infect them. Despite numerous classical studies and an abundance of genomics data, we still lack answers to basic questions about transcription in human cells. How does a promoter coordinate transcription in a complex environment. What controls the targeting and strength of enhancer-promoter pairs? In part, this is a problem of scale, as physical interactions in the human genome can span megabases and a single transcription factor may have thousands of target sites, making identifying all functional interactions extremely difficult.

My approach is to study these questions in nuclear-replicating DNA viruses, which contain host-like promoters, enhancers, repressors, and 3D structural elements within a compact, densely encoded genome. By using techniques built for human genomes spanning thousands of genes and billions of bases and applying them to an oncovirus encoding fewer than 100 genes across <200 kilobases, we have the power to exhaustively identify every possible regulatory element and answer basic and applied questions in transcription and virology.

My lab will use these approaches with two distinct goals in mind:

1. to build an understanding of transcriptional regulation encoded by the virus but following the human principles of gene expression and
2. to identify unique viral regulatory mechanisms whose disruption may allow specific targeting for therapeutic intervention (Figure 1).

Nuclear-replicating DNA viruses as human pathogens and unique models of transcriptional regulation. My lab studies Kaposi’s sarcoma-associated herpesvirus (KSHV) – an oncogenic human pathogen and a primary cause of cancer deaths in regions where it is endemic such as Southern and Central Africa. As a double-stranded DNA herpesvirus, it establishes lifelong infections and causes disease primarily in untreated HIV+ or other immunocompromised patients. KSHV’s closest relative – Epstein-Barr virus (EBV) – is itself associated with many cancers and has recently been identified as the primary etiologic agent of multiple sclerosis. Despite this widespread disease burden, there is no effective antiviral therapy for either virus. These viruses each cause widespread infections with serious medical issues in a fraction of infected individuals, and therefore there is a pressing need for new and more effective treatments. They also each have compact, densely encoded genomes and rely on host-like and viral-specific mechanisms of transcription that make them ideal models for the approach and goals of my lab.

Our initial studies will include:

• What is the core regulatory module controlling host-like KSHV transcription and how does this change when infecting different cell types?
• How do viral DNA replication factors and their regulatory sequences support viral-unique KHSV transcription?
• How does the virus hijack human transcriptional machinery to support host-like and viral-unique gene expression?

Selected Publications

1. Morgens DW, Gulyas L, Souza AS, Glaunsinger BA (2024) Enhancers and genome conformation provide complex transcriptional control of a herpesviral gene. Mol Syst Biol 21: 30 – 58 PMID: 39562742

2. Morgens DW, Nandakuma D, Didychuck AL, Yang KJ, Glaunsinger BA. (2022) A two-tiered functional screen identifies herpesviral transcriptional modifiers and their essential domains. PLoS Pathogens 18(1): e1010236. PMID: 35041709

Contact Us

LSU Health Shreveport
Department of Microbiology & Immunology
1501 Kings Hwy, Shreveport, LA 71103

Email: David.Morgens@lsuhs.edu