Research Interests:
Alzheimer's Disease
Amyotrophic Lateral Sclerosis (ALS)
Cellular Senescence
Geroscience
Mouse Models of Aging and Disease
Neurobiology of Aging
Spatial Biology
Tauopathy
Translational Research/Clinical Trials
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Research Interests
My research focuses on the molecular mechanisms of Alzheimer’s disease and the effects of tau accumulation on cellular senescence and risk for chronic neurodegenerative diseases. These studies span basic mechanistic approaches using animal and cell culture models, as well as multicenter human clinical trials. I have a part-time research appointment at the Salisbury VA Medical Center, and I am committed to educating the next generation of scientists as co-founder and director of the Translational Research in Aging and Alzheimer’s Disease course and through mentorship in my laboratory. My lab welcomes all inquisitive, respectful minds with a passion for research in brain aging and Alzheimer’s disease. We endorse diversity and do not tolerate discrimination. To influence positive changes, we first reflect on our own thoughts and behaviors, recognize and question our biases, and continually practice self-assessment to become better scientists, colleagues, and citizens. We foster a safe interpersonal research environment and encourage open, respectful communication that promotes knowledge, understanding, and overall growth in thought and behavior. The Orr lab believes that a happy, healthy, balanced work environment cultivates effective scientific ambassadors that positively impact biomedical research and our community.
Select Publications
Senolytic therapy in mild Alzheimer’s disease: a phase 1 feasibility trial.
Gonzales MM, Garbarino VR, Kautz T, Palavicini JP, Lopez-Cruzan M, Dehkordi SK, Mathews J, Zare H, Xu P, Zhang B, Franklin C, Habes, M Craft C, Petersen R, Tchkonia T, Kirkland J, Salardini A, Seshadri S, Musi N, Orr ME. Nat Med. 2023 Sep 7.
Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology. Dehkordi SK, Walker J, Sah E, Bennett E, Atrian F, Frost B, Woost B, Bennett RE, Orr TC, Zhou Y, Andhey PS, Colonna M, Sudmant PH, Xu P, Wang M, Zhang B, Zare H, Orr ME. Nat Aging. 2021 Dec;1 (12):1107-1116.
Tau protein aggregation is associated with cellular senescence in the brain.
Musi N, Valentine JM, Sickora KR, Baeuerle E, Thompson CS, Shen Q, Orr ME. Aging Cell. 2018 12; 17(6):e12840.
Differential protein expression in the hippocampi of resilient individuals identified by digital spatial profiling.
Walker JM, Kazempour Dehkordi S, Fracassi A, Vanschoiack A, Pavenko A, Taglialatela G, Woltjer R, Richardson TE, Zare H, Orr ME. Acta Neuropathol Commun. 2022 Feb 14; 10(1):23.
Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial.
Gonzales MM, Garbarino VR, Marques Zilli E, Petersen RC, Kirkland JL, Tchkonia T, Musi N, Seshadri S, Craft S, Orr ME.
J Prev Alzheimers Dis. 2022; 9(1):22-29
The landscape of human tissue and cell type specific expression and co-regulation of senescence genes.
Xu P, Wang M, Song WM, Wang Q, Yuan GC, Sudmant PH, Zare H, Tu Z, Orr ME, Zhang B. Mol Neurodegener. 2022 Jan 09; 17(1):5.
Biological aging processes underlying cognitive decline and neurodegenerative disease.
Gonzales MM, Garbarino VR, Pollet E, Palavicini JP, Kellogg DL, Kraig E, Orr ME. J Clin Invest. 2022 May 16; 132(10).
Research activities
and funding
New Investigator Award in Biology and Geroscience Research. Dec. 31, 2022 – Dec.r 31, 2025.
Hevolution/AFAR
Spatial proteogenomic profiling to determine the impact of senescent neurons on the aging brain.
Role: Principal Investigator
R01AG068293 (ORR, MIRANDA ETHEL) Sep 10, 2020 - May 31, 2025,
NIH
High-Resolution Profiling of Senescent Neurons and Their Microenvironments in Postmortem Human Brain Tissue Spanning Eight Decades of Life
Role: Principal Investigator
ORR, MIRANDA, ETHEL Mar 1, 2021 - Feb 29, 2024
Alzheimer’s Disease Drug Discovery Foundation
Phase II Clinical Trial to Evaluate the Safety and Feasibility of Senolytic Therapy in Alzheimer’s Disease.
Role: Principal Investigator
I01BX005717 (ORR, MIRANDA, ETHEL) Oct 1, 2022 - Sep 30, 2026
US Department of Veterans Affairs
High-Resolution Profiling of Senescent Cells in ALS Brain and Spinal Cord
Role: Principal Investigator
R24AG073199 (SHIVELY, CAROL A.) Sep 15, 2021 - May 31, 2025
NIH
Development of an Innovative Vervet (Chlorocebus aethiops sabaeus) Model of Early Alzheimer's-like Neuropathology and Symptomatology
Role: Co-Investigator
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R21NS125171 (MILLIGAN, CAROL) Sep 29, 2021 - Mar 28, 2023
NIH
Cell Senescence and Death in Neurodegenerative Diseases
Role: MPI
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R01AG065839 (SOLINGAPURAM SAI, KIRAN) Jan 15, 2020 - Dec 31, 2024
NIH
Evaluating microtubule binding as a potential imaging biomarker for Alzheimer's disease
Role: Co-Investigator
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