Dremel, Sarah
Primary Appointment
Assistant Professor, Microbiology, Immunology, and Cancer Biology
Education
- BS, Biochemistry; Genetics & Cellular Development, University of Minnesota
- PhD, Molecular Virology & Microbiology, University of Pittsburgh
- Postdoctoral fellowship, Cancer Virology, National Cancer Institute
Contact Information
Pinn Hall 4080
1340 Jefferson Park Ave
Charlottesville, VA 22908
Email: qdt2nz@virginia.edu
Research Disciplines
Bioinformatics and Genomics, Cancer Biology, Genetics, Infectious Diseases/Biodefense, Microbiology
Research Interests
Herpesvirus gene expression & RNA biology
Research Description
Overview. I work at the interface of virology and genetics to reveal core principles of viral and host gene expression. I seek to understand how viruses manipulate the transcriptional machinery (gene expression, splicing, decay) and the consequences this has for the host. To do so I employ high-throughput sequencing (HTS) and bioinformatic analysis tailored for infection models to develop an unbiased global picture of virus-driven changes. The mechanistic underpinnings of these observations are investigated with virology and molecular biology techniques.
Ongoing Research. My research centers on herpesviruses, including Herpes Simplex Virus-1 (HSV-1) and Kaposi sarcoma herpesvirus (KSHV). Herpesviruses are a major public health concern with individuals testing seropositive for at least three of the nine species by adulthood. Infection is asymptomatic for many individuals but, in cases of immune-compromise—such as transplant recipients, neonates, and those with HIV/AIDS—these viruses have devastating effects. HSV-1 commonly causes recurrent oral and genital lesions, but can also cause herpes keratitis, herpetic whitlow, and encephalitis. KSHV is an oncovirus and the etiological agent of its namesake Kaposi sarcoma. KSHV is also associated with lymphoproliferative disorders including primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). There are no FDA-approved vaccines for HSV-1 and KSHV. Additionally, we lack antivirals capable of targeting the latent reservoir and there is no therapeutic agent capable of clearing these viruses.
Herpesviruses have linear, double stranded, DNA genomes and replicate within the host nucleus, requiring the host transcription machinery for synthesis of their >100 viral RNAs. To prioritize viral transcripts, herpesviruses affect significant changes in all stages of gene expression. Like their host, herpesviruses express multiple types of RNAs including, messenger RNA, long noncoding RNA, microRNA, and circular RNA (circRNA). My recent work has centered on the biology of circRNAs, single-stranded RNAs circularized by 5’ to 3’ covalent linkages. While labeled an alternative splicing product, circRNAs are the predominant transcript isoform for certain genes. CircRNAs modulate gene expression as miRNA sponges, protein scaffolds, or transcriptional enhancers. They are not all noncoding, with published instances of cap-independent translation. CircRNAs have been historically understudied, as they share almost complete sequence identity with their colinear gene products. HTS and chimeric junction analysis has led to an exponential increase in our knowledge of circRNA biology. We now know circRNAs are ubiquitously expressed in an array of organisms, e.g. humans, mice, drosophila. Additionally, both RNA and DNA viruses express their own cohort of circRNAs.
Future research will address three main questions: 1) What are the key cis- and trans-acting factors driving viral circRNA biogenesis? 2) How does circularity influence the fate of these alternative splicing isoforms? 3) What is the functional role of circRNAs during infection, immunity, and tumorigenesis?
Personnel. The lab is hiring at all levels! Please email (qdt2nz@virginia.edu) if interested.