Sandra K. Weller

HSV-1 and -2 are large DNA virus which are responsible for oral and genital infections, sight-threatening ocular infections and brain infections which can be life threatening. Our laboratory uses genetic, biochemical, biophysical, structural and molecular approaches to elucidate mechanisms of synthesis, maturation and cleavage and packaging of viral genomes. One of our goals is to identify antiviral targets which can be exploited to develop strategies for controlling viral infections. Projects in the lab are diverse and include virus-host interactions important for the formation of replication compartments within the nucleus of infected cells; structure function analysis of two viral helicases; structure-function analysis of the zinc binding domain of the HSV-1 primase; analysis of the role of recombination in viral DNA replication and genome maturation and the analysis of the machinery involved in cleavage and packaging of viral genomes into preformed procapsids. Important recent discoveries include: The identification and characterization of a novel viral recombinase. The realization that host cell recombination and repair proteins are involved in HSV DNA synthesis. The discovery that host chaperones are rearranged in infected cells into foci which act as quality control mechanisms for the production of properly folded proteins. The finding that the initiation helicase-origin binding protein UL9 is degraded during infection in a ubiquitin mediated pathway. The further characterization of the interdependence of the helicase and primase subunits with each other.

[2025] Erlandsen, Heidi; Krucinska, Jolanta; Wilderman, P Ross; Makkay, Andrea M; Szczepaniak, Renata; Wright, Lee R; Weller, Sandra K; Wright, Dennis L. The crystal structure of the herpes virus ICP8 protein in complex with single-stranded DNA reveals the molecular determinants of nucleotide recognition. The Journal of biological chemistry. 2026 Mar;111366 [2025] Yu, Zishuo; Sathyanarayana, Pradeep; Liu, Cong; Tan, Joel M J; Yang, Pan; Das, Biswajit; Hu, Side; Fan, Xiaoyi; Ji, Chenggong; Weller, Sandra K; Shekhar, Mrinal; Coen, Donald M; Kranzusch, Philip J; Loparo, Joseph J; Abraham, Jonathan. Mechanisms of HSV-1 helicase-primase inhibition and replication fork complex assembly. Cell. 2025 Dec; [2025] Discipio, Katherine A; Krucinska, Jolanta; Szczepaniak, Renata; Erlandsen, Heidi; Makka