David J. Loane
David Loane, PhD, is an Assistant Professor of Anesthesiology and Faculty Member at the Center for Shock, Trauma and Anesthesiology Research (STAR) at the University of Maryland School of Medicine, Baltimore, Maryland. Dr. Loane conducted his graduate studies at the Department of Pharmacology and MRC Center for Synaptic Plasticity, University of Bristol, England, and obtained his PhD in Neuroscience in 2005. He then pursued postdoctoral training with Dr. Marina Lynch at Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland, where he studied neuroinflammatory changes in the aged and Alzheimer's disease (AD) brain. In 2007 Dr. Loane was recruited to the Department of Neuroscience, Georgetown University Medical Center, Washington D.C., to perform further postdoctoral training on experimental models of traumatic brain injury (TBI) under the mentorship of Dr. Alan Faden. He joined the faculty of the University of Maryland School of Medicine in November 2009 and is currently Assistant Professor of Anesthesiology.
Dr. Loane leads a multi-disciplinary research team dedicated to studying the complexities of TBI, neuroinflammation and tissue repair. Specifically, his research program investigates the activation status and functional role of resident microglia and infiltrating blood-borne monocytes (macrophages) in the TBI brain, and to determine how they contribute to chronic neurodegeneration and long-term neurological dysfunction after brain trauma. His group is seeking to elucidate the mechanisms that regulate microglial/macrophage polarization (M1/M2 activation states) with the goal of manipulating these cells to attenuate destructive pro-inflammatory (M1) responses, and promote protective repair (M2) responses. Ongoing studies include examining: 1) the function and phenotypes of microglia/macrophages following acute TBI, and how they contribute to chronic pathologies; 2) the signaling pathways that drive M2 polarization of microglia/macrophages, and whether these pathways can be manipulated after TBI; 3) how age affects microglia/macrophage polarization and the neuroinflammatory response after TBI. The mission of his group is to elucidate the pathophysiological mechanisms underlying post-traumatic neuroinflammation, neurodegeneration and loss of neurological function, and to develop novel treatment strategies that will translate to the clinic for human head injury.
A diverse array of in vitro and in vivo experimental models are used to study pathophysiological mechanisms of TBI and neurodegeneration. These include: controlled cortical impact (mice), fluid percussion injury (rats), transgenic mouse models, mechanical injury in primary cortical neurons/neuron-glia co-cultures, cell cultures (primary microglia, neurons, astrocytes; cell lines), immunohistochemistry and state-of-the-art microscopy (light/fluorescence/confocal) and image analysis (stereology), behavioral analysis (cognitive, motor, depression/anxiety function), FACS analysis, molecular biology (qPCR, Western), magnetic resonance imaging (T2-weighted, DTI).
Microglial Activation Phenotypes and Mechanisms of Repair in the Aged TBI Brain
NIH/NINDS R01 NS082308
09/30/13 – 07/31/17
The Effect of Voluntary Exercise on Microglial Activation Phenotypes in the Aged Injured Brain
NIH/NIA Claude D. Pepper Older Americans Independence Center (P30-AG028747)
- Alok Kumar, PhD
Post-doctoral Fellow, 2010-Present
- James P. Barrett, PhD
Post-doctoral Fellow, 2014-Present
- Mariely Alvarez, Msc.
Visiting PhD Student, 2015-Present
Selected peer-review articles
- Loane DJ, Pocivavsek A, Moussa CE-H, Thompson R, Matsuoka Y, Faden AI, Rebeck GW, Burns MP. APP secretases as therapeutic targets for traumatic brain injury. Nature Medicine. 2009 15 377-9. PMID 19287391.
- Loane DJ, Deighan BF, Clarke RM, Griffin RJ, Lynch AM, Lynch MA. Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain. Neurobiology of Aging. 2009 30 920-31. PMID 17950491.
- Loane DJ, Stoica BA, Pajoohesh-Ganji A, Byrnes KR, Faden AI. Activation of metabotropic glutamate receptor 5 (mGluR5) modulates microglial reactivity and neurotoxicity by inhibiting NADPH oxidase. Journal of Biological Chemistry. 2009 284 15629-15639. PMID 19634772.
- Loane DJ, Washington PM, Vardanian L, Pocivavsek A, Hoe HS, Duff KE, Cernak I, Rebeck GW, Faden AI, Burns MP. Modulation of ABCA1 by an LXR agonist reduces beta-amyloid levels and improves outcome after traumatic brain injury. Journal of Neurotrauma. 2011 28(2): 225-36. PMID 21975399.
- Kabadi SV, Stoica BA, Byrnes KR, Hanscom M, Loane DJ, Faden AI. Selective CDK inhibitor limits neuroinflammation and progressive neurodegeneration after brain trauma. Journal of Cerebral Blood Flow and Metabolism. 2012 32(1):137-49. PMID 21829212.
- Kabadi SV, Stoica BA, Loane DJ, Byrnes KR, Hanscom M, Cabatbat RM, Tan MT, Faden AI. Cyclin D1 gene ablation confers neuroprotection in traumatic brain injury. Journal of Neurotrauma. 2012 29(5):813-27. PMID 21895533.
- Kabadi SV, Stoica BA, Hanscom M, Loane DJ, Kharebava G, Murray MG II, Cabatbat RM, Faden AI. CR8, a Selective and Potent CDK Inhibitor, Provides Neuroprotection in Experimental Traumatic Brain Injury. Neurotherapeutics. 2012 9(2):405-21. PMID 22167461.
- Byrnes KR*, Loane DJ*, Stoica BA, Zhang Z, Faden AI. Delayed mGluR5 activation reduces chronic inflammation and neurodegeneration after brain trauma. Journal of Neuroinflammation. 2012 9:43. (*co-first author) PMID 22426396.
- Zhao Z, Loane DJ, Murray MG 2nd, Stoica BA, Faden AI. Comparing the predictive value of multiple cognitive, affective, and motor tasks after rodent traumatic brain injury. Journal of Neurotrauma. 2012 29(15):2475-89. PMID: 22924665.
- Piao CS, Loane DJ, Stoica BA, Li S, Hanscom M, Cabatbat RM, Blomgren K, Faden AI. Combined inhibition of cell death induced by apoptosis inducing factor and caspases provides additive neuroprotection in experimental traumatic brain injury. Neurobiology of Disease. 2012 46(3):745-58. PMID 22426396.
- Loane DJ, Stoica BA, Byrnes K, Jeong W, Faden AI. Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury. Journal of Neurotrauma. 2012 Nov 30. [Epub ahead of print] PMID: 23199080.
- Kumar A, Stoica BA, Sabirzhanov B, Burns MP, Faden AI, Loane DJ. Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states. Neurobiology of Aging. 2012 Dec 27 [Epub ahead of print]. PMID: 23273602.
- Piao CS, Stoica BA, Wu J, Sabirzhanov N, Zhao Z, Loane DJ, Faden AI. Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiology of Disease. 54 252-63, 2013.
- Winston CN, Chellappa D, Wilkins T, Barton DJ, Washington PM, Loane DJ, Zapple DN, Burns MP. Controlled cortical impact results in extensive loss of dendritic spines that is not associated with injury-induced amyloid beta accumulation. Journal of Neurotrauma. 30 1966-72, 2013.
- Zhao Z, Faden AI, Loane DJ, Lipinski MM, Sabirzhanov B, Stoica BA. Neuroprotective effects of geraylgeranylacetone in experimental traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism. 33 1897-1908, 2013.
- Loane DJ, Kumar A, Stoica BA, Cabatbat R, Faden AI. Progressive neurodegeneration after experimental brain trauma; association with chronic microglial activation. Journal of Neuropathology and Experimental Neurology. 73 14-29, 2014.
- Kabadi SV, Stoica BA, Loane DJ, Luo T, Faden AI. Cell cycle inhibition limits microglial activation, astrocytosis, neuronal loss and neurological dysfunction after experimental traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism. 34 502-13, 2014.
- Stoica BA, Loane DJ, Zhao Z, Kabadi SV, Hanscom M, Byrnes KR, Faden AI. PARP-1 inhibition attenuates neuronal loss, microglia activation and neurological deficits after traumatic brain injury. Journal of Neurotrauma. 31 758-772, 2014.
- Sabirzhanov B, Zhao Z, Stoica BA, Loane DJ, Wu J, Borroto C, Dorsey S, Faden AI. Down-regulation of miR-23a and miR-27a following experimental traumatic brain injury induces neuronal cell death through activation of pro-apoptotic Bcl-2 proteins. Journal of Neuroscience. 34 10055-71, 2014.
- Loane DJ, Stoica BA, Tchantchou F, Kumar A, Barrett JP, Akintola T, Xue F, Conn PJ, Faden AI. Novel mGluR5 positive allosteric modulator improves functional recovery, attenuates neurodegeneration, and alters microglial polarization after experimental TBI. Neurotherapeutics. 11 857-69, 2014.
Reviews, commentaries and book chapters
- Byrnes KR, Loane DJ, Faden AI. Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders. Neurotherapeutics. 2009 6(1):94-107. PMID: 19110202.
- Loane DJ, Byrnes KR. Role of microglia in neurotrauma. Neurotherapeutics. 2010 7(4):366-77. PMID: 20880501.
- Loane DJ, Faden AI. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends in Pharmacological Sciences. 2010 31(12):596-604. PMID: 21035878.
- Loane DJ, Stoica BA, Faden AI. Metabotropic glutamate receptor-mediated signaling in neuroglia. Wiley Interdisciplinary Reviews Membrane Transport and Signaling. 2012 1(2):136-150. PMID: 22662309.
- Kumar A, Loane DJ. Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behavior and Immunity. 2012 26(8):1191-201. PMID: 22728326.