Ashley is an Assistant Professor in the MCB Department. Her lab studies the molecular mechanisms of brain aging and neurodegeneration. Ashley received her B.Sc. from McGill University and her Ph.D. in Molecular and Cellular Biology from the University of Washington in 2007. She did her postdoctoral work at Stanford University.
|Babcock KR, Page JS, Fallon JR, Webb AE. "Adult Hippocampal Neurogenesis in Aging and Alzheimer's Disease." Stem Cell Reports, vol. 16, no. 4, 2021, pp. 681-693.|
|McCauley BS, Sun L, Yu R, Lee M, Liu H, Leeman DS, Huang Y, Webb AE, Dang W. "Altered Chromatin States Drive Cryptic Transcription in Aging Mammalian Stem Cells." Nature aging, vol. 1, no. 8, 2021, pp. 684-697.|
|Maybury‐Lewis, Sun Y., Brown, Abigail K., Yeary, Mitchell, Sloutskin, Anna, Dhakal, Shleshma, Juven‐Gershon, Tamar, Webb, Ashley E. "Changing and stable chromatin accessibility supports transcriptional overhaul during neural stem cell activation and is altered with age." Aging Cell, 2021.|
|Curley DE, Webb AE, Sheffler DJ, Haass-Koffler CL. "Corticotropin Releasing Factor Binding Protein as a Novel Target to Restore Brain Homeostasis: Lessons Learned From Alcohol Use Disorder Research." Frontiers in Behavioral Neuroscience, vol. 15, 2021, pp. 786855.|
|Audesse, Amanda J., Karashchuk, Galina, Gardell, Zachary A., Lakis, Nelli S., Maybury‐Lewis, Sun Y., Brown, Abigail K., Leeman, Dena S., Teo, Yee Voan, Neretti, Nicola, Anthony, Douglas C., Brodsky, Alexander S., Webb, Ashley E. "FOXO3 regulates a common genomic program in aging and glioblastoma stem cells." Aging and Cancer, vol. 2, no. 4, 2021, pp. 137-159.|
|Vonk WIM, Rainbolt TK, Dolan PT, Webb AE, Brunet A, Frydman J. "Differentiation Drives Widespread Rewiring of the Neural Stem Cell Chaperone Network." Molecular Cell, 2020.|
|Audesse AJ, Webb AE. "Mechanisms of enhanced quiescence in neural stem cell aging." Mechanisms of Ageing and Development, vol. 191, 2020, pp. 111323.|
|Maybury-Lewis SY, Webb AE. "Taking Prisoners: Vimentin Cages Capture Proteasomes during NSC Activation." Cell stem cell, vol. 26, no. 4, 2020, pp. 473-475.|
|Audesse AJ, Dhakal S, Hassell LA, Gardell Z, Nemtsova Y, Webb AE. "FOXO3 directly regulates an autophagy network to functionally regulate proteostasis in adult neural stem cells." PLoS Genetics, vol. 15, no. 4, 2019, pp. e1008097.|
|Audesse AJ, Webb AE. "Enhancing Lysosomal Activation Restores Neural Stem Cell Function During Aging." Journal of experimental neuroscience, vol. 12, 2018, pp. 1179069518795874.|
|Schäffner I, Minakaki G, Khan MA, Balta EA, Schlötzer-Schrehardt U, Schwarz TJ, Beckervordersandforth R, Winner B, Webb AE, DePinho RA, Paik J, Wurst W, Klucken J, Lie DC. "FoxO Function Is Essential for Maintenance of Autophagic Flux and Neuronal Morphogenesis in Adult Neurogenesis." Neuron, vol. 99, no. 6, 2018, pp. 1188-1203.e6.|
|Leeman DS, Hebestreit K, Ruetz T, Webb AE, McKay A, Pollina EA, Dulken BW, Zhao X, Yeo RW, Ho TT, Mahmoudi S, Devarajan K, Passegué E, Rando TA, Frydman J, Brunet A. "Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging." Science, vol. 359, no. 6381, 2018, pp. 1277-1283.|
|Atkinson EG, Audesse AJ, Palacios JA, Bobo DM, Webb AE, Ramachandran S, Henn BM. "No Evidence for Recent Selection at FOXP2 among Diverse Human Populations." Cell, vol. 174, no. 6, 2018, pp. 1424-1435.e15.|
|Brown AK, Webb AE. "Regulation of FOXO Factors in Mammalian Cells." Current Topics in Developmental Biology, vol. 127, 2018, pp. 165-192.|
|Kim SY, Webb AE. "Neuronal Functions of FOXO/DAF-16." Nutrition and healthy aging, vol. 4, no. 2, 2017, pp. 113-126.|
|Webb AE, Kundaje A, Brunet A. "Characterization of the direct targets of FOXO transcription factors throughout evolution." Aging Cell, 2016.|
|Ahlenius H, Chanda S, Webb AE, Yousif I, Karmazin J, Prusiner SB, Brunet A, Südhof TC, Wernig M. "FoxO3 regulates neuronal reprogramming of cells from postnatal and aging mice." Proceedings of the National Academy of Sciences, vol. 113, no. 30, 2016, pp. 8514-9.|
|Webb AE, Brunet A. "FOXO transcription factors: key regulators of cellular quality control." Trends in biochemical sciences, vol. 39, no. 4, 2014, pp. 159-69.|
|Gopinath SD, Webb AE, Brunet A, Rando TA. "FOXO3 promotes quiescence in adult muscle stem cells during the process of self-renewal." Stem Cell Reports, vol. 2, no. 4, 2014, pp. 414-26.|
|Brunet A, Mahmoudi S, Mancini E, Rafalski VA and Webb AE. "Longevity pathways in mammalian cells." Annual review of gerontology & geriatrics, edited by Richard Sprott, Springer-Verlag, 2014.|
|Webb AE, Brunet A. "FOXO flips the longevity SWItch." J. Geophys. Res., vol. 15, no. 5, 2013, pp. 444-6.|
|Webb AE, Pollina EA, Vierbuchen T, Urbán N, Ucar D, Leeman DS, Martynoga B, Sewak M, Rando TA, Guillemot F, Wernig M, Brunet A. "FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis." Cell Reports, vol. 4, no. 3, 2013, pp. 477-91.|
|Wapinski OL, Vierbuchen T, Qu K, Lee QY, Chanda S, Fuentes DR, Giresi PG, Ng YH, Marro S, Neff NF, Drechsel D, Martynoga B, Castro DS, Webb AE, Südhof TC, Brunet A, Guillemot F, Chang HY, Wernig M. "Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons." Cell, vol. 155, no. 3, 2013, pp. 621-35.|
|Calnan DR, Webb AE, White JL, Stowe TR, Goswami T, Shi X, Espejo A, Bedford MT, Gozani O, Gygi SP, Brunet A. "Methylation by Set9 modulates FoxO3 stability and transcriptional activity." Aging, vol. 4, no. 7, 2012, pp. 462-79.|
|Brett JO, Renault VM, Rafalski VA, Webb AE, Brunet A. "The microRNA cluster miR-106b~25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation." Aging, vol. 3, no. 2, 2011, pp. 108-24.|
|Renault VM, Rafalski VA, Morgan AA, Salih DA, Brett JO, Webb AE, Villeda SA, Thekkat PU, Guillerey C, Denko NC, Palmer TD, Butte AJ, Brunet A. "FoxO3 regulates neural stem cell homeostasis." Cell stem cell, vol. 5, no. 5, 2009, pp. 527-39.|
|Webb AE, Driever W, Kimelman D. "psoriasis regulates epidermal development in zebrafish." Developmental dynamics : an official publication of the American Association of Anatomists, vol. 237, no. 4, 2008, pp. 1153-64.|
|Webb AE, Sanderford J, Frank D, Talbot WS, Driever W, Kimelman D. "Laminin alpha5 is essential for the formation of the zebrafish fins." Developmental Biology, vol. 311, no. 2, 2007, pp. 369-82.|
|Webb AE, Kimelman D. "Analysis of early epidermal development in zebrafish." Methods in Molecular Biology, vol. 289, 2005, pp. 137-46.|
|Pyati UJ, Webb AE, Kimelman D. "Transgenic zebrafish reveal stage-specific roles for Bmp signaling in ventral and posterior mesoderm development." Development, vol. 132, no. 10, 2005, pp. 2333-43.|
|Lemieux J, Lakowski B, Webb A, Meng Y, Ubach A, Bussière F, Barnes T, Hekimi S. "Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria." Genetics, vol. 159, no. 1, 2001, pp. 147-57.|
Aging is the major risk factor for a number of diseases, including neurodegeneration and several types of cancer. Yet, our understanding of the mechanisms responsible for aging at the molecular level remains limited. Identifying the factors that accelerate the aging process, as well as those that confer resilience, will influence quality of life in the elderly and lead to treatments for age-associated diseases. The focus of my research is on the molecular mechanisms of brain aging. We take an interdisciplinary approach to study physiological aging and age-associated disease, using a combination of mouse models, cell culture approaches, and genomics technologies. More specifically, I investigate the epigenetic and transcriptional mechanisms that preserve healthy cellular function, and how changes in these processes impair cellular processes in the aged brain. One major line of investigation is to discover the mechanisms that support the formation of new neurons from stem cells in the adult brain. We have made key discoveries on how relatively dormant stem cells in the brain accumulate damage with age and in disease models. Additionally, we are investigating the gene expression programs that promote healthy aging and are conserved across species. In this work, we have linked chromatin changes to gene expression networks that are critical for the cellular stress response and inflammation, which are key contributors to aging. Most recently, we have extended our work to models of Alzheimer’s disease and applied cutting-edge technologies such as single cell transcriptomics to delve into mechanisms of aging and disease at the single cell level. In the long-term, my work will advance our understanding of the molecular and cellular mechanisms that accelerate brain aging, and reveal new strategies to promote healthy aging and prevent age-associated disease.
Current Research Support
R01 AG053268 (NIH/NIA)
Webb, Ashley (PI)
Molecular mechanisms underlying the preservation of neural stem cell quiescence during aging.
04/01/17 – 03/31/22
R21 AG070527 (NIH/NIA)
Webb, Ashley (PI)
A new model system for studying brain aging and neurodegeneration.
09/11/20 – 09/10/22
R01 AG073411 (NIH/NIA)
Webb, Ashley (PI)
Pioneer transcription factors in aging and neurodegeneration.
08/15/21 – 05/31/26
R21 AG073743 (NIH/NIA)
Webb, Ashley (co-I; MPI with J. Fallon)
Promoting adult hippocampal neurogenesis in Alzheimer’s Disease models
07/01/21 – 06/30/23
Completed Research Support
P20 GM109035 (NIH/NIGMS)
Webb, Ashley (Pilot Award Recipient; PI - Rand, David)
COBRE Center for Computational Biology of Human Disease (Pilot Award: Genome-wide interplay between the pro-longevity FOXO transcription factors.)
Rhode Island Foundation Medical Research Grant
Webb, Ashley (PI)
Regulation of human neural stem cell function by the pro-longevity factor FOXO3.
U19 AG023122-10 (NIH/NIA)
Webb, Ashley (Sub-project PI; PIs - Cummings, SR and Melov, S)
Integrative Resource to Develop Translational Strategies to Promote Longevity (Sub-project: Genome-wide cell type specfic networks regulated by the pro-longevity FOXO3 transcription factor.)
Glenn Award for Research in Biological Mechanisms of Aging
Webb, Ashley (PI)
American Federation for Aging Research Junior Faculty Research Grant
Webb, Ashley (PI)
Preservation of adult neural stem cells by the pro-longevity FOXO3 transcription factor during aging
RI-INBRE Early Career Development Award
Webb, Ashley (sub-project PI)
Identification of transcription factor networks that preserve neural stem cells
|Postdoctoral Fellow||Stanford University, Genetics||2008-2014|
Salomon Faculty Research Award, Brown University, 2016.
Glenn Award for Research in Biological Mechanisms of Aging, 2015.
American Federation for Aging Research Junior Faculty Grant, 2015.
American Federation for Aging Research Postdoctoral Fellowship, 2012.
Keystone Symposium Scholarship, Adult Neurogenesis, 2011.
National Research Service Award, Cancer Biology Postdoctoral Fellowship, Stanford University,
Dean’s Fellowship, Stanford University, 2008.
|BIOL 0500 - Cell and Molecular Biology|
|BIOL 1970A - Stem Cell Biology|
|BIOL 2340 - Neurogenetics and Disease|