Nora Gray Lab
Lab overview
Lab overview
Mitochondrial dysfunction, oxidative stress and neuroinflammation are all interrelated processes that contribute to the cognitive impairment seen in aging and neurodegenerative disease. Therapies that can improve any one of these factors can therefore have a dramatic effect on enhancing cognitive performance and perhaps also on slowing disease progression. Many botanically-derived compounds can modulate these cellular processes and new advances in synthetic compounds offer the potential for additional precision of effects.
The overall goal of our research is to use mouse models to identify cognitive enhancing therapies with strong translational potential for eventual use in patient populations with neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD) as well as healthy elderly individuals. We take a broad and highly collaborative approach to identifying potential therapeutics, combining a variety of behavioral assessments of different domains of cognitive function with sophisticated analyses of mitochondrial function, antioxidant response, neuroinflammation and disease pathology.
If you’re interested in joining the lab as a post-doctoral fellow, graduate student or research assistant please email Nora (grayn@ohsu.edu). The Gray lab values and supports diversity in alignment with OHSU’s policy to honor, respect, embrace and value of all employees, patients, students and volunteers regardless of age, color, culture, disability, ethnicity, gender identity or expression, marital status, national origin, race, religion, sex, sexual orientation and socio-economic status.
Lab members
Lab members
Nora Gray, Ph.D.
Principal Investigator
Nora is interested in how metabolism and antioxidant activity are changed in normal aging as well as disease states and how these processes can be modulated by therapeutic interventions. She did her graduate work at the University of California, Berkeley in the department of Molecular and Biochemical Nutrition before coming to OHSU for her postdoctoral training as part of the Complementary and Alternative Medicine (CAM) in Neuroscience and Stress T32 training fellowship.
In 2017 she joined the faculty in the Neurology Department at OHSU as an Assistant Professor. She is part of the Botanical’s Enhancing Neurological and Functional Resilience in Aging (BENFRA) botanical research center where she is the lead of one of the research projects and also a member of the executive committee.
Nora also serves as a faculty member for the Neuroscience Graduate Program and a member of the Layton Aging and Alzheimer’s Disease Research Center. She is also the chair of the Department of Neurology DEI committee and the co-Director of the OADRC Biomarker Core.
Outside of the lab, Nora enjoys gardening, ultimate frisbee, crossword puzzles and playing guitar.
Sam Varada
Senior Research Assistant
Sam completed both her B.S. and M.S. in Microbiology at Oregon State University under Dr. Maude David. Her work involved the study of commensal gut microbiota and gut sensory cells to uncover the mechanisms of direct interactions within the multifaceted umbrella of the microbiota-gut-brain axis. Her research interests include the neuromodulatory effects of gut microbes and other alternative medical treatments. In 2023, Sam joined Dr. Nora Gray’s lab where she has been involved in projects related to both conventional and botanically-derived therapies. Outside the lab, you’ll most likely find Sam at one of Oregon’s many incredible disc golf courses or hiking trails.
Wyatt Hack
Research Assistant
Wyatt started at OHSU as an intern in the Apprenticeships in Science & Engineering program through Saturday Academy in the summer of 2013 in the lab of Dr. John Crabbe, studying the heritability of alcohol use disorders and possible treatments for alcoholism in mice. She received an Associate of Science from Portland Community College in 2017 and worked with Dr. Crabbe as a research assistant until his retirement in 2019.
Since 2020, Wyatt has been working in the labs of Dr. Gray as well as Dr. Joseph Quinn, assisting in the research of Alzheimer’s disease using mouse models of behavior and pathology. In the Gray lab she has been working on projects investigating the use of botanical treatments in neurodegenerative disease, which include research into the benefits of Centella asiatica consumption on cognition and the treatment of Parkinson’s disease with a derivative of the Gardenia resinifera plant. Her hobbies outside of the lab include reading, writing, and listening to podcasts.
Noah Gladen-Kolarsky
Research Assistant
Noah completed his B.S. in biology at the University of Denver in 2021. After a period of working with patients diagnosed with neurodegenerative illness, he began working as an RA in the Gray lab in the spring of 2022. Since joining the lab, his focus has primarily been on evaluating potential Alzheimer’s and Parkinson’s therapies in mouse models. Noah plans to continue with his education in the field of neurodegenerative disorders in graduate school at some point in the future. Outside the lab, he enjoys camping, reading and hockey.
Olivia Monestime
Research Assistant
Olivia earned her BS in Biology with minors in Psychology and Interdisciplinary Neuroscience from Portland State University in 2023. She initially came to the Gray lab as an undergraduate as part of the BUILD EXITO program but her passion for AD research urged her to transition to a research assistant role following graduation.
In the lab, Olivia aids in projects testing the efficacy of differing botanical compounds in mitigating the neurodegenerative effects of Alzheimer's disease. In the future, Olivia intends to pursue graduate degrees in neurobiology, as well as social work, to consolidate her varied interests in the brain, its health, and its impact on our lives.
Outside of the lab, Olivia spends time with her pet mouse, Effie, but she can also be found reading, crocheting, making clothes or music.
Lab alumni
Steve Chamberlin, N.D., MOTH, M.S. (Post-doctoral researcher 2021–2023)
Current position: K08 recipient at OHSU
Alex Speers, N.D., M.S. (Post-doctoral researcher 2020–2023)
Current position: KL2 recipient at OHSU
Cody Neff, B.S. (Research Assistant 2022–2023)
Current position: Sales associate at Aflac
Jon Zweig, B.S. (Senior Research Assistant 2017–2022)
Current position: Senior Research Associate at OHSU
Mikah Brandes, B.S. (EXITO researcher 2018–2020 and Research assistant 2021–2022)
Current position: Manufacturing associate at Twist Bioscience
Don Matthews, Ph.D. (Postdoctoral researcher 2017–2019)
Current position: Lab manager in the tech industry
Projects
Botanical interventions for aging and neurodegenerative disease
Plants offer a rich source of compounds with the potential to modulate antioxidant, mitochondrial and inflammatory pathways. Our current work focuses on three botanical compounds and extracts.
Centella asiatica: Centella asiatica (L) Urban is a plant that is used in Ayurvedic and traditional Chinese medicine to, among other things, boost memory and improve mental function. We have been studying a water extract of the plant called CAW and found that it improves learning, memory and executive function in mouse models of aging and Alzheimer’s disease. As part of our work with the BENFRA center we have been optimizing dosing concentration and route of administration and identifying translationally relevant plasma and neuroimaging biomarkers in the context of healthy aging.
We are also continuing our work with CAW in mouse models of Alzheimer’s disease. We have started to incorporate multiphoton in vivo imaging technology to investigate the effects of CAW on mitochondrial function and oxidative stress near β-amyloid (Aβ) plaques in our Alzheimer’s disease mice.
Withania Somnifera: Withania somnifera, also known as Ashwagandha, is a medicinal plant used in Ayurvedic medicine as a rejuvenating herb. It is also a popular dietary supplement taken to improve sleep, anxiety and cognitive function. Ashwagandha is classified as an adaptogen meaning it promotes homeostasis of the whole body through complex physiological mechanisms. The BENFRA center has been studying various Ashwagandha extracts in Drosophila melanogaster and neuronal cultures to investigate its effects on endpoints relevant to age-related changes in cognition, sleep, anxiety and depression. Our lab has recently started a study in our Aβ overexpressing mice to determine the effects of ashwagandha on memory and depression.
Gardenin A: Gardenin A is a compound found in the gum of Gardenia resinifera Roth. Our collaborators in the Ciesla lab at the University of Alabama identified the compound as neuroprotective in their Drosophila model of Parkinson’s disease. We have been evaluating Gardenin A in an α-synuclein-overexpressing mouse model of Parkinson’s disease where we have observed potent effects on mobility and cognitive function that appear to be mediated by effects on antioxidant response, inflammatory signaling and tyrosine hydroxylase expression. Our ongoing work is attempting to more specifically elucidate its mechanism of action.
Conventional/Drug interventions in Neurodegenerative Disease
Our work also involves collaborations with labs developing novel synthetic interventions to improve outcomes in neurodegenerative diseases. Currently we are working with Dr. Thomas Scanlan’s lab to evaluate his TREM2-activating compound, Sob-AM2, in two of our mouse models of Alzheimer’s disease. We will investigate the effects of this compound on cognition and AD pathology while also profiling its effects on microglial subpopulations via RNAseq and confirming the absence of off target peripheral effects using a variety of biochemical and behavioral assays.
Bench to Bedside Targeting of NRF2
The antioxidant regulatory protein NRF2 has emerged in recent years as a promising therapeutic target in aging and neurodegenerative disease. Our own work has demonstrated that loss of NRF2 accelerates age-related cognitive decline and mitochondrial dysfunction. We are currently developing novel mouse strains to explore the consequences of loss of NRF2 on disease progression in Alzheimer’s and Parkinson’s disease mice.
We are also interested in determining the translational utility of using NRF2 expression in blood cells as a biomarker in neurodegenerative disease. We have several ongoing collaborations that support this area of research in the context of Alzheimer’s disease, Parkinson’s disease and multiple sclerosis.
Publications
Selected publications
2023
Xu Q, Yang W, Zhong M, Lin Z, Gray NE, Xian Y. (2023) Animal models of Alzheimer’s disease: preclinical insights and challenges. Acta Materia Medica, in press.
2022
Quinn JF, Kelly MJ, Harris CJ, Hack W, Gray NE, Kulik V, Bostick Z, Brumbach BH, Copenhaver PF. (2022) The novel estrogen modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer’s Disease. Neurobiology of Disease, 174: 105888.
Gray N, Farina M, Tucci P, Saso L. (2022) The role of the NRF2 pathway in maintaining and improving cognitive function. Biomedicines, 10 (8): 2043.
Wright KM, Bollen M, David J, Speers AB, Brandes MS, Gray NE, Alcazar Magana A, McClure C, Stevens JF, Maier CS, Quinn JF, Soumyanath A (2022) Pharmacokinetics and pharmacodynamics of key components of a standardized Centella asiatica product in cognitively impaired older adults: A phase 1, double-blind, randomized clinical trial. Antioxidants, 11(2): 11020215.
Cabey K, Long D, Law A, Gray NE, McClure C, Caruso M, Lak P, Wright KM, Stevens JF, Soumyanath A, Kretzschmar D. (2022) Withania somnifera and Centella asaitica extracts ameliorate behavioral deficits in an in vivo Drosophila melanogaster model of oxidative stress. Antioxidants, 11(1): 121.
Khorani M, Bobe G, Matthews DG, Alcazar Magana A, Caruso M, Gray NE, Quinn JF, Stevens JF, Soumyanath A, Maier CS (2022) The Impact of the hAPP695SW Transgene and Associated Aβ Accumulation on Murine Hippocampal Biochemical Pathways. Journal of Alzheimer’s Disease, 85(4): 1601-1619.
2021
Brandes MS, Zweig JA, Tang A, Gray NE. (2021) NRF2 activation ameliorates oxidative stress and improves mitochondrial function and synaptic plasticity in A53T α-synuclein hippocampal neurons. Antioxidants, 11(1): 26.
Speers AB, Garcia-Jaramillo M, Feryn A, Matthews DG, Lichtenberg T, Caruso M, Wright KM, Quinn JF, Stevens JF, Maier CS, Soumyanath A, Gray NE. (2021) Centella asiatica alters metabolic pathways associated with Alzheimer’s disease in the 5xFAD Mouse Model of β-Amyloid Accumulation. Frontiers Pharmacology, 12: 788312.
Arituluk ZC, Horne J, Adhikari B, Steltzner J, Mansur S, Ahirwar P, Velu SE, Gray NE, Ciesla LM, Bao Y. (2021) Identification of TrkB Binders from Complex Matrices Using a Magnetic Drug Screening Platform. ACS Applied Bio Materials, 4: 6244-6255.
Zweig JA, Brandes MS, Brumbach B, Caruso M, Wright KM, Quinn JF, Soumyanath A, Gray NE. (2021) Loss of NRF2 leads to accelerated cognitive decline, exacerbated mitochondrial dysfunction and is required for cognitive enhancing effects of Centella asiatica during aging. Neurobiology of aging.100: 48-58.
Zweig JA, Brandes MS, Brumbach BH, Caruso M, Wright KM, Quinn JF, Soumyanath A, Gray NE. (2021) Prolonged treatment with Centella asiatica improves memory, reduces AB pathology and activates NRF2-regulated antioxidant response pathway in 5xFAD mice. Journal of Alzheimer's Disease. 81(4)1453-1468.
2020
Neilson LE, Quinn JF, Gray NE. (2020) Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease. Antioxidants. 10(1):28.
Brandes MS, Gray NE. (2020) NRF2 as a therapeutic target in neurodegenerative diseases. ASN Neuro. 12: 1-23.
Matthews DG, Caruso M, Alcazar Magana A, Wright KM, Maier CS, Stevens JF, Gray NE, Quinn JF, Soumayanath A. (2020) Caffeoylquinic acids in Centella asiatica reverse cognitive deficits in male 5XFAD Alzheimer’s disease model mice. Nutrients. 12(11):3488.
Alcazar Magana A, Wright K, Vaswani A, Caruso M, Reed RL, Bailey CF, Nguyen T, Gray NE, Soumyanath A, Quinn J, Stevens JF, Maier CS. (2020) Integration of mass spectral fingerprinting analysis with precursor ion (MS1) quantification for the characterization of botanical extracts: application to extracts of Centella asiatica (L.) Urban. Phytochem Anal. 31(6) 722-738.
Harris CJ, Gray NE, Caruso M, Hunter M, Ralle, M Quinn JF. (2020) Copper Modulation and Memory Impairment due to Hippocampal Tau Pathology. Journal of Alzheimer’s Disease. 78(1):49-60.
2019
Harris CJ, Davis B, Zweig JA, Nevonen KA, Quinn JF, Carbone L, Gray NE. (2019) Age-associated DNA methylation patterns are shared between the hippocampus and peripheral blood cells. Epigenomics and Epigenetics. 11: 111
Zweig JA, Caruso M, Brandes MS, Gray NE. (2019) Loss of NRF2 leads to impaired mitochondrial function, decreased synaptic density and exacerbated age-related cognitive deficits. Experimental gerontology. 131: 110767.
Matthews DG, Caruso M, Murchison CF, Zhu JY, Wright KM, Harris CJ, Gray NE, Quinn JF, Soumyanath A. (2019) Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice. Antioxidants 8 (12), 630.
Waslo C, Bourdette D, Gray N, Wright K, Spain R. Lipoic Acid and Other Antioxidants as Therapies for Multiple Sclerosis. (2019) Curr Treat Options Neurol. 21(6):26.
2018
Gray NE, Zweig JA, Caruso M, Zhu JY, Wright KM, Quinn JF, Soumyanath A. (2018) Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid overexpressing mice. Molecular and Cellular Neuroscience, 93:1-9.
Gray NE, Zweig JA, Caruso M, Martin MD, Zhu JY, Quinn JF, Soumyanath A. (2018) Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice. Brain and Behavior. 8(7): e01024
Lou JS, Dimitrova DM, Murchison C, Arnold GC, Belding H, Seifer N, Le N, Andrea SB, Gray NE, Soumyanath A. (2018) Centella asiatica triterpenes for diabetic neuropathy: a randomized, double-blind, placebo-controlled, pilot clinical study. Dermatological Experiences, 20 (suppl 1, no 1), 12-22.
Gray NE, Alcazar A, Lak P, Wright K, Quinn, JF, Stevens, JF, Soumyanath A, Maier CS. (2018) Centella asiatica - Phytochemistry and mechanisms of neuroprotection and cognitive enhancement. Phytochemical Reviews. 17 (1) 161-194.
2017
Gray NE, Zweig JA, Matthews D, Quinn JF, Soumyanath A. (2017) Centella asiatica attenuates Aβ-induced mitochondrial dysfunction and oxidative stress in isolated hippocampal neurons. Oxidative Medicine and Cellular Longevity. 7023091.
Gray NE, Zweig JA, Murchison C, Caruso M, Matthews DG, Kawamoto C, Harris CJ, Quinn JF, Soumyanath A. (2017) Centella asiatica attenuates Aβ – induced neurodegenerative spine loss and dendritic simplification. Neuroscience Letters, 646: 24-29.
2016
Gray NE, Harris CJ, Quinn JF, Soumyanath A. (2016) Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function in mice. Journal of Ethnopharmacology, 180: 71-86
Gray NE, Zweig JA, Kawamoto C, Quinn JF, Copenhaver PF. (2016) STX, a novel membrane estrogen receptor ligand, protects against Aβ toxicity. Journal of Alzheimer’s Disease, 51 (2): 391-403.
2015
Gray NE, Quinn JF. (2015) Alterations in mitochondrial number and function in Alzheimer’s disease fibroblasts. Metabolic Brain Disease, 30(5):1275-8.
Gray NE, Sampath H, Zweig JA, Quinn, JF, Soumyanath A. (2015) Centella asiatica attenuates Aβ-induced oxidative stress and mitochondrial dysfunction. Journal of Alzheimer’s Disease, 45(3):933-46.
2014
Gray NE, Morré J, Kelley J, Maier CS, Stevens JF, Quinn JF, Soumyanath A. (2014) Caffeoylquinic Acids in Centella asiatica Protect against Amyloid-β Toxicity. Journal of Alzheimer’s Disease, 40: 359–373.
Lab photos
