I and You by Lauren Gunderson Directors Book

During the height of the COVID-19 pandemic, producing live theatre was put on an indefinite hold, and the theatre world had to turn to other means of production including virtual performances, much like the production of I and You by Lauren Gunderson that was produced as a part of the Studio 115 Spring 2021 season and was directed by Sarah Hogestyn. This project is an extensive virtual documentation of the directing process, the rehearsal process, and the shift from producing theatre live to producing it virtually. Follow along with every step of the process from the standpoint of the director in this new world of distanced theatre

Human Herpesvirus 6A Latency Gene U94A Impairs Motility and Maturation in Central Nervous System Cell Types: Implications for Neurodegenerative Disease

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Neuroscience Graduate Program, 2020.Many neurodegenerative diseases have a multifactorial etiology and variable course of progression that cannot be explained by current models. Neurotropic viruses have long been suggested to play a role in these diseases, although their exact contributions remain unclear. Human herpesvirus 6A (HHV-6A) is one of the most common viruses detected in the adult brain, and has been clinically associated with multiple sclerosis (MS), and, more recently, Alzheimer’s disease (AD). HHV-6A is a ubiquitous viral pathogen capable of infecting glia and neurons. Primary infection in childhood is followed by the induction of latency, characterized by expression of the U94A viral transcript in the absence of viral replication. Our work is the first to examine the effects of this common viral gene on cells of the central nervous system. We found that U94A expression inhibits the migration and maturation of human oligodendrocyte precursor cells (OPCs) without affecting their viability, a phenotype that may contribute to the failure of remyelination seen in many patients with MS. Large-scale transcriptomics and proteomics analyses indicate that U94A expression in OPCs alters the expression of genes involved in cytoskeletal regulation and in cellular interactions with the extracellular matrix, while preliminary biochemical analyses suggest that U94A may exert its functions by interacting with nucleosomes and with myosin motors. As HHV-6A seems to be significantly associated with early AD pathology, we extended our initial analysis of U94A in OPCs to cytoskeletal abnormalities in neurons. We found that U94A expression inhibits morphological maturation in human cortical neurons. Given that morphological abnormalities are known to precede synapse loss and cognitive impairment in AD patients, we hypothesize that U94A expression in neurons renders them more susceptible to dysfunction and degeneration. Our work suggests that the persistent presence of HHV-6A-associated proteins establishes a state of vulnerability that can contribute to disease progression in MS and AD. We propose this virus as a unique human factor to consider in the translation of therapies from animal models to human patients

Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology

Human herpesviruses (HVs) have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system (CNS). The ability of HVs to enter a state of latency, a defining characteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease (NDD) pathology by highlighting two prominent members of the HV family, herpes simplex virus 1 (HSV-1) and human herpesvirus 6 (HHV-6). We (i) introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then (ii) review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer's disease (AD) and multiple sclerosis (MS), respectively. We then (iii) highlight and discuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we (iv) discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs

Expression of the Human Herpesvirus 6A Latency-Associated Transcript U94A Disrupts Human Oligodendrocyte Progenitor Migration

Progression of demyelinating diseases is caused by an imbalance of two opposing processes: persistent destruction of myelin and myelin repair by differentiating oligodendrocyte progenitor cells (OPCs). Repair that cannot keep pace with destruction results in progressive loss of myelin. Viral infections have long been suspected to be involved in these processes but their specific role remains elusive. Here we describe a novel mechanism by which HHV-6A, a member of the human herpesvirus family, may contribute to inadequate myelin repair after injury