Frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are devastating neurodegenerative disorders that cause progressive brain damage and impairments in cognitive function and behavior. The underlying causes of FTD and AD are not clear and effective treatments are urgently needed to stop or reverse disease progression. Growing evidence points to altered glial-neuronal interactions, neuroimmune responses, and mitochondrial dysregulation as crucial aspects of these disorders. Greater insight into glial and mitochondrial pathobiology may hold the keys to prevention and effective treatment for FTD and AD and potentially other CNS conditions that have common underlying mechanisms.
Glial cells, including astrocytes, are abundant non-neuronal cells that represent about half of the brain. Astrocytes are crucial for brain function but their exact signaling mechanisms and roles are not well-defined. The Orr lab is investigating how astrocytes enable and modulate brain function and how they participate in disease pathogenesis. Some key questions include: What are the effects of astrocyte signaling on neuronal activities and cognitive processes? What are the pathobiological changes and roles of astrocytes in aging, neurodegenerative disorders, and behavioral deficits in disease? How can we harness astrocyte-neuronal interactions to treat neurocognitive disorders?
The Orr lab is also investigating mitochondrial production of reactive oxygen species (also known as free radicals) and their contributions to glial-neuronal interactions and neurodegenerative disorders. Main questions include: How are reactive oxygen species produced in neural cells in health and disease? How do reactive oxygen species affect normal signaling pathways and what are their roles in brain aging and neurodegenerative disorders? Can precise blockade of their production reduce or prevent disease?
Across different research projects, the Orr lab aims to discover new fundamental and disease-related neural mechanisms and translate their findings into promising treatments for neurological disorders. The lab uses a variety of approaches, including behavioral analyses, transgenic models and cell cultures, electrophysiology, molecular biology, and omic approaches, including transcriptomics, translatomics, proteomics, and lipidomics. The Orr lab welcomes inquiries from graduate students and postdoctoral fellows passionate about neuroscience, unraveling mechanisms of disease, and contributing to a supportive and collaborative research environment.
- Mechanisms of disease
- Cell signaling
Dr. Orr’s research training focused on cellular and behavioral neuroscience and neurodegenerative disorders. As a graduate student at Emory University with Dr. Stephen Traynelis and subsequently a postdoctoral fellow at the Gladstone Institutes and UCSF with Dr. Lennart Mucke, Dr. Orr explored astrocytic and microglial signaling and uncovered new molecular pathways regulating glial chemotaxis, scavenging, and proliferation in brain injury. Her postdoctoral studies revealed that astrocyte receptor activity influences neurocognitive function and can promote cognitive decline. Dr. Orr was appointed faculty in the Weill Cornell Graduate Program in 2018 and was named Nan and Stephen Swid Assistant Professor of Frontotemporal Dementia Research in 2021.
- 2021: Outstanding Neuroscience Teaching and Mentoring Award, Weill Cornell Graduate School
- 2021: Nan and Stephen Swid Endowed Professorship of Frontotemporal Dementia Research
- 2021: Accelerating Drug Discovery for FTD Grant from AFTD and ADDF