Moriah Szpara is an Associate Professor in the Department of Biology and the Department of Biochemistry and Molecular Biology and the Huck Institutes for the Life Sciences, at the Pennsylvania State University (PSU). Dr. Szpara is a member of the Center for Infectious Disease Dynamics (CIDD) at Penn State, and organizes the Virology @ PSU network. Dr. Szpara's early training began with her B.S. in Biology at PSU, with honors theses in Biology and Anthropology. Dr. Szpara was then awarded a Ph.D. in Molecular and Cell Biology from the University of California Berkeley, for her studies on the transcriptional programs underlying neuronal development. As a postdoctoral fellow at Princeton University, Dr. Szpara trained with Dr. Lynn Enquist in the area of neurotropic herpes viruses, and initiated her research on viral comparative genomics in the Lewis-Sigler Institute for Integrative Genomics.
The Szpara lab at Penn State is focused on dissecting viral genetic contributions to virulence, the contributions of viral diversity in clinical and field settings, and the molecular interactions of herpes simplex virus (HSV) with host neurons. The szpara lab uses approaches that range from genomics and bioinformatics analyses of viral genetic variation, to humane neuronal cell responses to infection. The Szpara lab has also produced open-source software packages to facilitate herpes virus genome assembly and comparison, including VirAmp and VirGA.
- Spear Colloquium Lecturer, given in honor of National Academy of Sciences member, Dr. Patricia Spear, Northwestern University, Chicago, IL (2018)
- Priscilla Schaffer Memorial Award & Lectureship, annual award to a young investigator in the area of herpes virus research, International Herpes Virus Workshop (IHW, 2017)
- Daniel R. Tershak Memorial Teaching Award, for excellence in teaching, the Pennsylvania State University (2017)
- National Institutes of Health Research Scholar Development Award, Career Transition Award (K22; 2013)
A variety of viruses infect the human nervous system, often with severe consequences. While vaccines have largely defeated the paralysis caused by polio, other viruses such as rabies, West Nile virus, and herpes simplex virus (HSV) continue to cause neurological infections that require clinical intervention. More than 70% of adults in the United States carry HSV, whether they know it or not. HSV causes recurrent genital and oral lesions (e.g. cold sores), and in rare cases can progress to cause potentially fatal brain infections. Although not all of those infected experience noticeable symptoms, human hosts have a permanent relationship with this virus. HSV has a unique ability to establish lifelong latency in neurons. The consequences of HSV latency for the neurons that harbor this pathogen are not well understood. Our laboratory aims to address this question and search for improved therapeutics using a combination of virology, neurobiology, next generation sequencing technologies, and bioinformatics.
Viral variation and neurovirulence
The Szpara lab studies genetic variation and adaptability in HSV, a major cause of human disease. We use high-throughput sequencing to reveal viral variation genome-wide and to assess viral population diversity within any given viral stock or clinical sample. We have developed several bioinformatics pipelines to speed the assembly of viral genomes and teh comparison of sequences across groups of viral isolates. To understand links between viral genetic variation and the phenotypes associated with these differences, we use a variety of in vitro cell culture models (e.g. infections of epithelial and neuronal cells) an in vivo mouse models (e.g.development of neuropathology in experimentally infected mice). We use these model systems to characterize the phenotypic differences caused by viral genetic variations. To address the human clinical side of viral infection, we have established collaborations with clinicians whose expertise includes both adult and neonatal consequences of HSV-1 infection. We anticipate that differences in viral virulence genes contribute to the differing symptoms and severity of HSV disease in humans. If this data can be linked to human impacts in the future, the ability to gauge likelt virulence level based on viral genotype would provide a powerful tool for future diagnostics or prediction of clinical outcomes. This data may also enable the development of strain-specific therapeutics or antiviral management strategies.
Neuronal consequences of infection
We would like to better understand how HSV latency affects the host neuron and its neighboring cells. In lab experiments, HSV infection of neurons has been associated with changes in neuropeptide release, neuronal firing rates, axon remodeling, and interferon production. HSV-1 infection has been shown to impact the main molecular markers of Alzheimer's disease (AD) neuropathology: the extracellular plaques formed by amyloid beta (Aβ) and intracellular neurofibrillary tangles formed by phosphorylated tau. While neurons are not specialized for immune control or attack, they do contain intrinsic cellular defenses. How are these cellular defenses and immune responses triggered by neurons during HSV infection? What is the viral counter-attack? Are neuronal defenses activated during viral reactivation, or only during the initial round of infection? Features unique to neurons may present novel targets to block the progression of infection, or to mitigate infection-induced damage that play a role in long-term outcomes such as Alzheimer's disease. We address the neurobiology of infection using a combination of neuronal cultures,in vivo models of infection, and high-throughput measurements of the host response.