Dimitrios Davalos, PhD
Assistant Staff
Assistant Professor, Molecular Medicine, CCLCM-CWRU
Email: [email protected]
Location: Cleveland Clinic Main Campus
Research
Dr. Dimitrios Davalos studies the neuro-immune mechanisms that influence the brain’s normal function, its homeostatic balance, and its structural integrity. He is particularly interested in microglia, the resident immune cells of the brain, the spinal cord and the retina, the three major sites of the central nervous system (CNS). His research aims to determine the cellular and molecular mechanisms through which microglia facilitate normal brain function, and regulate immune responses when the homeostasis or the integrity of the CNS are pathologically compromised. In doing so, his ultimate goal is to identify new targets for therapeutic intervention for neurological diseases.
During his graduate years Dr. Davalos performed the first in vivo imaging study of microglia, taking advantage of advanced microscopy technologies that allow following the behavior of individual cells inside the intact living brain, in real time. He demonstrated that microglia continuously survey the intact brain, and can rapidly contain small localized injuries within just a few minutes. These findings challenged prior views regarding the role of microglia in the brain, and inspired numerous new studies aimed at better understanding the mechanisms and the significance of such unexpected microglial abilities for neuronal development, plasticity, function, and dysfunction.
In recent years, Dr. Davalos has been studying microglial responses in the context of blood brain barrier disruption, a phenomenon that is very common among pathologies such as multiple sclerosis, stroke, and other neurodegenerative diseases. He has also developed and published novel methods for imaging the living brain and spinal cord to follow ongoing biological processes over time. His research combines cutting-edge imaging techniques with molecular, cellular and genetic approaches to study the interactions between blood vessels, neurons, and glia, and understand how their functional and structural relationships change between health and disease.
Biography
Dr. Davalos earned a B.S. in Biology from the University of Athens in Greece, and a Ph.D. in Physiology and Neuroscience from New York University. He did his postdoctoral training at the University of California, San Diego (UCSD), and the Gladstone Institute of Neurological Disease at the University of California, San Francisco (UCSF). Prior to joining the Lerner Research Institute and Cleveland Clinic, Dr. Davalos served as the associate director of the Center for In Vivo Imaging Research at the Gladstone Institutes and UCSF. He reviews for several scientific journals and funding institutions and maintains an active role in training the next generation of neuro-immunologists and glio-vascular biologists. He has organized and regularly participates in International scientific conferences, and currently serves as the program chair for the Spring Brain Conferences. He previously received postdoctoral and young investigator awards from the National Multiple Sclerosis Society, the American Heart Association and the Race to Erase Multiple Sclerosis Foundation. His lab is currently funded by the National Institute of Neurological Disorders and Stroke, the National Institute on Alcohol Abuse and Alcoholism, and the National Multiple Sclerosis Society.
Education & Professional Highlights
Appointed
2015
Fellowship - University of California-San Francisco
Postdoc Fellow, Gladstone Institute of Neurological Dis.
San Francisco, CA USA
2010
Fellowship - University of California-San Diego
Postdoc Fellow in Department of Pharmacology
La Jolla, CA USA
2008
Doctorate - New York University School of Medicine
Neuroscience and Physiology
New York, NY USA
2005
Undergraduate - National University of Athens
Biology
Athens, Greece
2000
Research
We study the role that neuroimmune mechanisms play in brain function under physiological conditions and during neurological disease. Our main cells of interest are microglia, the resident immune cells of the central nervous system. Microglia are the first responders to any pathological insult—whether injury or disease— but their role in the physiological brain was greatly underappreciated for decades. Moreover, microglia have also historically been synonymous with inflammatory processes that can further damage neurons in the context of disease.
Using advanced microscopy technologies to follow the behavior of individual cells inside the intact living brain in real time, we previously showed—for the first time—that microglia continuously survey their environment and can rapidly contain small injuries within a few minutes without causing inflammatory damage. These findings inspired numerous studies aimed at understanding the mechanisms and the significance of such unexpectedly dynamic microglial functions for neuronal development, plasticity, function, and dysfunction.
Our recent studies have focused on microglial responses in the context of blood-brain barrier disruption, a pathological phenomenon that is very common among neurological diseases such as multiple sclerosis, Alzheimer’s disease, and stroke. We have also developed and published novel methods for imaging the living brain and spinal cord to follow ongoing biological processes over time. Our research combines cutting-edge imaging techniques with molecular, cellular and genetic approaches to study the interactions between blood vessels, neurons, and glia, and to better understand how their structural and functional relationships change between health and disease. By studying these relationships in real time, our ultimate goal is to expand our understanding of the role of microglia in brain function, and to identify new targets for therapeutic intervention for neurological diseases.
Our Team
Selected Publications
View publications for Dimitrios Davalos, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)
- Crockett A, Fuhrmann M, Garaschuk O, Davalos D. (2024) Progress in Structural and Functional In Vivo Imaging of Microglia and Their Application in Health and Disease. Adv Neurobiol. 2024:37:65-80. PMID: 39207687
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Profaci CP, Harvey SS, Bajc K, Zhang TZ, Jeffrey DA, Zhang AZ, Nemec KM, Davtyan H, O’Brien CA, McKinsey GL, Longworth A, McMullen TP, Capocchi JK, Gonzalez JG, Lawson DA, Arnold TD, Davalos D, Blurton-Jones M, Dabertrand F, Bennett FC, Daneman R. (2024) Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism. Neuron August 13. doi:https://doi.org/10.1016/j.neuron.2024.07.015.
- Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, Amit I, Audinat E, Bechmann I, Bennett M, Bennett F, Bessis A, Biber K, Bilbo S, Blurton-Jones M, Boddeke E, Brites D, Brône B, Brown GC, Butovsky O, Carson MJ, Castellano B, Colonna M, Cowley SA, Cunningham C, Davalos D, De Jager PL, de Strooper B, Denes A, Eggen BJL, Eyo U, Galea E, Garel S, Ginhoux F, Glass CK, Gokce O, Gomez-Nicola D, González B, Gordon S, Graeber MB, Greenhalgh AD, Gressens P, Greter M, Gutmann DH, Haass C, Heneka MT, Heppner FL, Hong S, Hume DA, Jung S, Kettenmann H, Kipnis J, Koyama R, Lemke G, Lynch M, Majewska A, Malcangio M, Malm T, Mancuso R, Masuda T, Matteoli M, McColl BW, Miron VE, Molofsky AV, Monje M, Mracsko E, Nadjar A, Neher JJ, Neniskyte U, Neumann H, Noda M, Peng B, Peri F, Perry VH, Popovich PG, Pridans C, Priller J, Prinz M, Ragozzino D, Ransohoff RM, Salter MW, Schaefer A, Schafer DP, Schwartz M, Simons M, Smith CJ, Streit WJ, Tay TL, Tsai LH, Verkhratsky A, von Bernhardi R, Wake H, Wittamer V, Wolf SA, Wu LJ, Wyss-Coray T. (2022) Microglia states and nomenclature: A field at its crossroads. Neuron Nov 2;110(21):3458-3483. doi: 10.1016/j.neuron.2022.10.020. PMID: 36327895.
- Tognatta R, Merlini M, Yan Z, Schuck R, Davalos D, Akassoglou K. (2021) In vivo two-photon microscopy protocol for imaging microglial responses and spine elimination at sites of fibrinogen deposition in mouse brain. STAR Protoc. 2(3):100638. PMID: 34258598; PMCID: PMC8259313
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Turaga SM, Silver DJ, Bayik D, Paouri E, Peng S, Lauko A, Alban TJ, Borjini N, Stanko S, Naik U, Keri RA, Connor JR, Barnholtz-Sloan JS, Rubin JB, Berens M, Davalos D, Lathia JD. (2020) JAM-A functions as a female microglial tumor suppressor in glioblastoma. Neuro Oncol. 22(11):1591-1601. PMID: 32592484; PMCID: PMC7690368
- Soulet D, Lamontagne-Proulx J, Aubé B, Davalos D. (2020) Multiphoton intravital microscopy in small animals: motion artefact challenges and technical solutions. J Microsc. 278(1):3-17. PMID: 32072642; PMCID: PMC7187339
- Borjini N, Paouri E, Tognatta R, Akassoglou K, Davalos D. (2019) Imaging the dynamic interactions between immune cells and the neurovascular interface in the spinal cord. Exp Neurol. 322:113046. PMID: 31472115; PMCID: PMC7328885
- Davalos D, Mahajan KR, Trapp BD. (2019) Brain fibrinogen deposition plays a key role in MS pathophysiology - Yes. Mult Scler. Jul 18:1352458519852723. PMID: 31315512
- Merlini M, Rafalski VA, Rios Coronado PE, Gill TM, Ellisman M, Muthukumar G, Subramanian KS, Ryu JK, Syme CA, Davalos D, Seeley WW, Mucke L, Nelson RB, Akassoglou K. (2019) Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer's Disease Model. Neuron pii: S0896-6273(19)30015-7. PMID: 30737131; PMCID:PMC6602536
- Ryu JK, Rafalski VA, Meyer-Franke A, Adams RA, Poda SB, Rios Coronado PE, Pedersen LØ, Menon V, Baeten KM, Sikorski SL, Bedard C, Hanspers K, Bardehle S, Mendiola AS, Davalos D, Machado MR, Chan JP, Plastira I, Petersen MA, Pfaff SJ, Ang KK, Hallenbeck KK, Syme C, Hakozaki H, Ellisman MH, Swanson RA, Zamvil SS, Arkin MR, Zorn SH, Pico AR, Mucke L, Freedman SB, Stavenhagen JB, Nelson RB, Akassoglou K. (2018) Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration. Nat Immunol. 19(11):1212-1223. PMID: 30323343; PMCID: PMC6317891
- Sayed FA, Telpoukhovskaia M, Kodama L, Li Y, Zhou Y, Le D, Hauduc A, Ludwig C, Gao F, Clelland C, Zhan L, Cooper YA, Davalos D, Akassoglou K, Coppola G, Gan L. (2018) Differential effects of partial and complete loss of TREM2 on microglial injury response and tauopathy. Proc Natl Acad Sci USA 115(40):10172-10177. PMID: 30232263; PMCID: PMC6176614
- Krabbe G, Minami SS, Etchegaray JI, Taneja P, Djukic B, Davalos D, Le D, Lo I, Zhan L, Reichert MC, Sayed F, Merlini M, Ward ME, Perry DC, Lee SE, Sias A, Parkhurst CN, Gan WB, Akassoglou K, Miller BL, Farese RV Jr, Gan L. (2017) Microglial NFκB-TNFα hyperactivation induces obsessive-compulsive behavior in mouse models of progranulin-deficient frontotemporal dementia. Proc Natl Acad Sci USA 114(19):5029-5034. doi: 10.1073/pnas.1700477114. PMID: 28438992; PMCID: PMC5441749
- Tsai HH, Niu J, Munji R, Davalos D, Chang J, Zhang H, Tien AC, Kuo CJ, Chan JR, Daneman R, Fancy SP. (2016) Oligodendrocyte precursors migrate along vasculature in the developing nervous system. Science 351(6271):379-84. PMID: 26798014; PMCID: PMC5472053
- Akassoglou K, Agalliu D, Chang CJ, Davalos D, Grutzendler J, Hillman EM, Khakh BS, Kleinfeld D, McGavern DB, Nelson SJ, Zlokovic BV. (2016) Neurovascular and Immuno-Imaging: From Mechanisms to Therapies. Proceedings of the Inaugural Symposium. Front Neurosci 10:46. PMID: 26941593; PMCID: PMC4761864
- Baeza-Raja B, Sachs BD, Li P, Christian F, Vagena E, Davalos D, Le Moan N, Ryu JK, Sikorski SL, Chan JP, Scadeng M, Taylor SS, Houslay MD, Baillie GS, Saltiel AR, Olefsky JM, Akassoglou K. (2016) p75 Neurotrophin Receptor Regulates Energy Balance in Obesity. Cell Rep 14(2):255-68. PMID: 26748707; PMCID: PMC4831919
- Le Moan N, Baeten KM, Rafalski VA, Ryu JK, Rios Coronado PE, Bedard C, Syme C, Davalos D, Akassoglou K. (2015) Hypoxia Inducible Factor-1α in Astrocytes and/or Myeloid Cells Is Not Required for the Development of Autoimmune Demyelinating Disease. eNeuro 2(2). PMID: 26213713; PMCID: PMC4511492
- Gyoneva S, Davalos D, Biswas D, Swanger SA, Garnier-Amblard E, Loth F, Akassoglou K, Traynelis SF. (2014) Systemic inflammation regulates microglial responses to tissue damage in vivo. Glia 62(8):1345-60. PMID: 24807189; PMCID: PMC4408916
- Davalos D, Baeten KM, Whitney MA, Mullins ES, Friedman B, Olson ES, Ryu JK, Smirnoff DS, Petersen MA, Bedard C, Degen JL, Tsien RY, Akassoglou K. (2014) Early detection of thrombin activity in neuroinflammatory disease. Ann Neurol 75(2):303-8. PMID: 24740641; PMCID: PMC4049631
- Chen W, Guo Y, Walker EJ, Shen F, Jun K, Oh SP, Degos V, Lawton MT, Tihan T, Davalos D, Akassoglou K, Nelson J, Pile-Spellman J, Su H, Young WL. (2013) Reduced mural cell coverage and impaired vessel integrity after angiogenic stimulation in the Alk1-deficient brain. Arterioscler Thromb Vasc Biol 33(2):305-10. PMID: 23241407; PMCID: PMC3569037
- Merlini M, Davalos D, Akassoglou K. (2012) In vivo imaging of the neurovascular unit in CNS disease. Intravital 1(2):87-94. PMID: 25197615; PMCID: PMC4155511
- Davalos D, Ryu JK, Merlini M, Baeten KM, Le Moan N, Petersen MA, Deerinck TJ, Smirnoff DS, Bedard C, Hakozaki H, Gonias Murray S, Ling JB, Lassmann H, Degen JL, Ellisman MH, Akassoglou K. (2012) Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun 3:1227. PMID: 23187627; PMCID: PMC3514498
- Kwan W, Träger U, Davalos D, Chou A, Bouchard J, Andre R, Miller A, Weiss A, Giorgini F, Cheah C, Möller T, Stella N, Akassoglou K, Tabrizi SJ, Muchowski PJ. (2012) Mutant huntingtin impairs immune cell migration in Huntington disease. J Clin Invest 122(12):4737-47. PMID: 23160193; PMCID: PMC3533551
- Baeza-Raja B, Li P, Le Moan N, Sachs BD, Schachtrup C, Davalos D, Vagena E, Bridges D, Kim C, Saltiel AR, Olefsky JM, Akassoglou K. (2012) p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity. Proc Natl Acad Sci U S A 109(15):5838-43. PMID: 22460790; PMCID: PMC3326459
- Davalos D, Akassoglou K. (2012) In vivo imaging of the mouse spinal cord using two-photon microscopy. J Vis Exp Jan 5;(59):e2760. PMID: 22258623; PMCID: PMC3369767
- Davalos D, Akassoglou K. (2012) Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 34(1):43-62. PMID: 22037947
- Drew PJ, Shih AY, Driscoll JD, Knutsen PM, Blinder P, Davalos D, Akassoglou K, Tsai PS, Kleinfeld D. (2010) Chronic optical access through a polished and reinforced thinned skull. Nat Methods 7(12):981-4. PMID: 20966916; PMCID: PMC3204312
- Ryu JK, Davalos D, Akassoglou K. (2009) Fibrinogen signal transduction in the nervous system. J Thromb Haemost 7 Suppl 1:151-4. PMID: 19630789; PMCID: PMC2888044
- Davalos D, Lee JK, Smith WB, Brinkman B, Ellisman MH, Zheng B, Akassoglou K. (2008) Stable in vivo imaging of densely populated glia, axons and blood vessels in the mouse spinal cord using two-photon microscopy. J Neurosci Methods 169(1):1-7. PMID: 18192022; PMCID: PMC2647134
- Adams RA, Schachtrup C, Davalos D, Tsigelny I, Akassoglou K. (2007) Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: lessons from multiple sclerosis. Curr Med Chem 14(27):2925-36. PMID: 18045138
- Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8(6):752-8. PMID: 15895084
Careers
Research News
In normal conditions, healthy blood vessels provide a physical border between the brain and circulating blood known as the blood-brain barrier (BBB). The barrier becomes compromised very early in MS.
