The Sariyer Lab at the Lewis Katz School of Medicine, Temple University, is dedicated to investigating the intricate molecular and cellular mechanisms that underlie viral infections, substance abuse, and neurodegenerative disorders affecting the central nervous system (CNS). Our research primarily focuses on human viruses such as HIV, HSV and JC virus, examining how these pathogens contribute to neurological diseases, and how drugs of abuse, particularly opioids, exacerbate CNS injury, inflammation, and cognitive decline. In parallel, we explore neurodegenerative diseases such as Alzheimer’s disease (AD), aiming to uncover shared pathological pathways influenced by viral infections and opioid exposure.
A cornerstone of our research is the study of alternative pre-mRNA splicing, a critical gene regulatory mechanism that modulates the diversity and function of proteins in cells. We investigate how viruses hijack host splicing machinery to regulate their own gene expression and replication, and how dysregulation of splicing contributes to viral persistence and pathogenesis. Similarly, our lab examines the impact of opioids and neurodegenerative processes on alternative splicing patterns within neurons and glial cells, which can alter cellular function and promote neurotoxicity in addiction and AD. We seek to unravel how viral regulatory proteins, opioids, and neurodegenerative stressors disrupt RNA processing pathways, contributing to synaptic dysfunction, neuroinflammation, and neuronal death. Understanding these splicing alterations offers new insights into the molecular basis of neuroinfectious and neurodegenerative diseases and identifies novel targets for therapeutic intervention.
To model these complex interactions, we utilize cutting-edge 2D neuronal cultures and 3D cerebral organoids derived from human induced pluripotent stem cells (iPSCs). These systems recapitulate the cellular diversity and architecture of the human brain, providing powerful platforms to study virus-host interactions, opioid effects, and neurodegenerative mechanisms in physiologically relevant environments.
Our lab also leverages CRISPR/Cas9 gene editing technology to precisely manipulate genes involved in viral replication, RNA splicing regulation, and neuronal function. This approach enables us to dissect the roles of specific viral and host factors in neuropathology and to develop potential gene-editing therapies aimed at disrupting viral reservoirs or correcting pathological splicing events associated with opioid addiction and Alzheimer’s disease.
By integrating neurovirology, addiction biology, neurodegeneration research, RNA biology, and advanced gene editing, the Sariyer Lab strives to identify novel molecular targets and develop innovative therapeutic strategies. Our ultimate goal is to translate these discoveries into effective diagnostics, treatments, and preventive measures that improve brain health and cognitive function in individuals affected by neuroinfectious diseases, substance abuse, and neurodegeneration.
Through collaborative and interdisciplinary research efforts, the Sariyer Lab continues to advance the understanding of CNS diseases and foster the development of next-generation therapies for some of the most pressing neurological health challenges today.