We use multipronged experimental methods to unravel astrocyte pathobiology and astrocytic roles in cognitive function and behavior and define how changes in astrocytes influence disease and may represent new therapeutic targets for effective intervention to prevent dementia.
Dementia is a progressive multifactorial disorder and the only top cause of death that cannot be effectively treated or prevented. It will impact future generations with increasing magnitude and represents one of the biggest health challenges of our time.
We believe that basic and translational science can steer the course toward effective treatment and prevention of dementia and other devastating disorders of the brain. Dementia involves multiple converging pathobiological pathways. Impairments in glial functions and glial-neuronal interactions are emerging as central drivers of dementia and other CNS disorders. Our primary goal is to harness astrocytic functions and astrocytic-neuronal interactions to treat and prevent neurological disease, including frontotemporal dementia (FTD) and Alzheimer's disease (AD).
Recent Achievements of the Orr Lab: Discovered that astrocytic production of mitochondrial reactive oxygen species (mtROS) is site-specific, regulated by neuroimmune signaling, and causes selective changes in protein oxidation and gene expression linked to neurodegenerative disorders.
Established that astrocytic mtROS produced by complex III amplifies tauopathy associated with FTD and other dementias.
Uncovered FTD/AD-linked changes in astrocytic TDP-43 that disrupt antiviral signaling and promote selective neuronal vulnerability and progressive cognitive decline.
Established that inflammatory signaling can engage cell stress pathways, induce stress granule formation, and alter nucleocytoplasmic dynamics in astrocytes.
Determined that astrocytic release of chemokines and activation of neuronal chemokine receptors regulates presynaptic function and hippocampal transmission.
Found that astrocytic G protein-coupled receptor signaling modulates cognitive function in a bidirectional and sex-dimorphic manner.
Identified astrocytic glutamate receptor mGluR3 as an important regulator of spatial memory and goal-oriented search behavior.
Biography
Dr. Adam Orr received his Ph.D. in Neuroscience from Emory University under the guidance of Dr. Xiao-Jiang Li, where he studied mitochondrial transport in Huntington’s disease. He then trained with Dr. Martin Brand at the Buck Institute for Research on Aging where he explored mitochondrial reactive oxygen species and discovered novel molecules that selectively block the production of reactive oxygen species. He has also worked at the Gladstone Institutes and collaborated with two start-up companies to therapeutically correct mitochondrial dysfunction in disease. He has been generously supported by the Sanofi iAward, NIA, NINDS, BrightFocus Foundation, the Association for Frontotemporal Degeneration, and the Daedalus Fund for Innovation from the BioPharma Alliances and Research Collaborations at WCM. He is currently Assistant Professor of Neuroscience at Weill Cornell Medicine and has been honored with the Mentor of the Year Award from the Weill Cornell Neuroscience department.
