Laura L. Dugan, M.D.

Professor

laura.l.dugan@vanderbilt.edu
Faculty Appointments
Professor of Medicine Abram C. Shmerling, M.D. Chair in Alzheimer's and Geriatric Medicine
Education
M.D., Medicine, Ohio State University, Columbus, OhioS.B., Massachusetts Institute of Technology, Cambridge, Massachusetts
Office Address
2215 Garland Avenue
Light Hall 529
Nashville, TN 37232
Research Keywords
aging, age-related, inflammation, innate immunity, autophagy, mitophagy, mitochondria, neuroscience, Parvalbumin inhibitory neurons, glutamate receptors, neurodegenerative diseases, fullerenes, PET imaging, interleukin-6, Stat3, confocal fluorescence microscopy, EPR, cell culture, in vivo.
Publications
Dugan LL, Tian L, Quick KL, Hardt JI, Karimi M, Brown C, Loftin S, Flores H, Moerlein SM, Polich J, Tabbal SD, Mink JW, Perlmutter JS. Carboxyfullerene neuroprotection postinjury in Parkinsonian nonhuman primates. Ann. Neurol [print-electronic]. 2014 Sep; 76(3): 393-402. PMID: 25043598, PMCID: PMC4165715, DOI: 10.1002/ana.24220, ISSN: 1531-8249.

Chu W, Chepetan A, Zhou D, Shoghi KI, Xu J, Dugan LL, Gropler RJ, Mintun MA, Mach RH. Development of a PET radiotracer for non-invasive imaging of the reactive oxygen species, superoxide, in vivo. Org. Biomol. Chem. 2014 Jul 7/7/2014; 12(25): 4421-31. PMID: 24847866, PMCID: PMC4122299, DOI: 10.1039/c3ob42379d, ISSN: 1477-0539.

Dugan LL, You YH, Ali SS, Diamond-Stanic M, Miyamoto S, DeCleves AE, Andreyev A, Quach T, Ly S, Shekhtman G, Nguyen W, Chepetan A, Le TP, Wang L, Xu M, Paik KP, Fogo A, Viollet B, Murphy A, Brosius F, Naviaux RK, Sharma K. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J. Clin. Invest [print-electronic]. 2013 Nov; 123(11): 4888-99. PMID: 24135141, PMCID: PMC3809777, PII: 66218, DOI: 10.1172/JCI66218, ISSN: 1558-8238.

Canzoniero LM, Granzotto A, Turetsky DM, Choi DW, Dugan LL, Sensi SL. NNOS(+) striatal neurons, a subpopulation spared in Huntington's Disease, possess functional NMDA receptors but fail to generate mitochondrial ROS in response to an excitotoxic challenge. Front Physiol. 2013; 4: 112. PMID: 23720635, PMCID: PMC3655281, DOI: 10.3389/fphys.2013.00112, ISSN: 1664-042X.

Naviaux RK, Zolkipli Z, Wang L, Nakayama T, Naviaux JC, Le TP, Schuchbauer MA, Rogac M, Tang Q, Dugan LL, Powell SB. Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. PLoS ONE [print-electronic]. 2013; 8(3): e57380. PMID: 23516405, PMCID: PMC3596371, PII: PONE-D-12-33298, DOI: 10.1371/journal.pone.0057380, ISSN: 1932-6203.

Pamenter ME, Ali SS, Tang Q, Finley JC, Gu XQ, Dugan LL, Haddad GG. An in vitro ischemic penumbral mimic perfusate increases NADPH oxidase-mediated superoxide production in cultured hippocampal neurons. Brain Res [print-electronic]. 2012 May 5/3/2012; 1452: 165-72. PMID: 22459046, PMCID: PMC3326196, PII: S0006-8993(12)00440-4, DOI: 10.1016/j.brainres.2012.03.004, ISSN: 1872-6240.

Ali SS, Hsiao M, Zhao HW, Dugan LL, Haddad GG, Zhou D. Hypoxia-adaptation involves mitochondrial metabolic depression and decreased ROS leakage. PLoS ONE [print-electronic]. 2012; 7(5): e36801. PMID: 22574227, PMCID: PMC3344937, PII: PONE-D-11-06211, DOI: 10.1371/journal.pone.0036801, ISSN: 1932-6203.

Hall DJ, Han SH, Chepetan A, Inui EG, Rogers M, Dugan LL. Dynamic optical imaging of metabolic and NADPH oxidase-derived superoxide in live mouse brain using fluorescence lifetime unmixing. J. Cereb. Blood Flow Metab [print-electronic]. 2012 Jan; 32(1): 23-32. PMID: 21847136, PMCID: PMC3323297, PII: jcbfm2011119, DOI: 10.1038/jcbfm.2011.119, ISSN: 1559-7016.

Ali SS, Young JW, Wallace CK, Gresack J, Jeste DV, Geyer MA, Dugan LL, Risbrough VB. Initial evidence linking synaptic superoxide production with poor short-term memory in aged mice. Brain Res [print-electronic]. 2011 Jan 1/12/2011; 1368: 65-70. PMID: 21075081, PMCID: PMC3018762, PII: S0006-8993(10)02493-5, DOI: 10.1016/j.brainres.2010.11.009, ISSN: 1872-6240.

Ali SS, Marcondes MC, Bajova H, Dugan LL, Conti B. Metabolic depression and increased reactive oxygen species production by isolated mitochondria at moderately lower temperatures. J. Biol. Chem [print-electronic]. 2010 Oct 10/15/2010; 285(42): 32522-8. PMID: 20716522, PMCID: PMC2952254, PII: M110.155432, DOI: 10.1074/jbc.M110.155432, ISSN: 1083-351X.

Douglas RM, Ryu J, Kanaan A, Del Carmen Rivero M, Dugan LL, Haddad GG, Ali SS. Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction. Am. J. Physiol., Cell Physiol [print-electronic]. 2010 Jun; 298(6): C1594-602. PMID: 20357179, PMCID: PMC2889641, PII: ajpcell.00298.2009, DOI: 10.1152/ajpcell.00298.2009, ISSN: 1522-1563.

Dugan LL, Ali SS, Shekhtman G, Roberts AJ, Lucero J, Quick KL, Behrens MM. IL-6 mediated degeneration of forebrain GABAergic interneurons and cognitive impairment in aged mice through activation of neuronal NADPH oxidase. PLoS ONE [print-electronic]. 2009; 4(5): e5518. PMID: 19436757, PMCID: PMC2678193, DOI: 10.1371/journal.pone.0005518, ISSN: 1932-6203.

Behrens MM, Ali SS, Dugan LL. Interleukin-6 mediates the increase in NADPH-oxidase in the ketamine model of schizophrenia. J. Neurosci. 2008 Dec 12/17/2008; 28(51): 13957-66. PMID: 19091984, PMCID: PMC2752712, PII: 28/51/13957, DOI: 10.1523/JNEUROSCI.4457-08.2008, ISSN: 1529-2401.

Ali SS, Hardt JI, Dugan LL. SOD activity of carboxyfullerenes predicts their neuroprotective efficacy: a structure-activity study. Nanomedicine [print-electronic]. 2008 Dec; 4(4): 283-94. PMID: 18656425, PMCID: PMC2651828, PII: S1549-9634(08)00083-X, DOI: 10.1016/j.nano.2008.05.003, ISSN: 1549-9642.

Cuddihy SL, Ali SS, Musiek ES, Lucero J, Kopp SJ, Morrow JD, Dugan LL. Prolonged alpha-tocopherol deficiency decreases oxidative stress and unmasks alpha-tocopherol-dependent regulation of mitochondrial function in the brain. J. Biol. Chem [print-electronic]. 2008 Mar 3/14/2008; 283(11): 6915-24. PMID: 18180306, PII: M702572200, DOI: 10.1074/jbc.M702572200, ISSN: 0021-9258.

Quick KL, Ali SS, Arch R, Xiong C, Wozniak D, Dugan LL. A carboxyfullerene SOD mimetic improves cognition and extends the lifespan of mice. Neurobiol. Aging [print-electronic]. 2008 Jan; 29(1): 117-28. PMID: 17079053, PII: S0197-4580(06)00342-3, DOI: 10.1016/j.neurobiolaging.2006.09.014, ISSN: 1558-1497.

Behrens MM, Ali SS, Dao DN, Lucero J, Shekhtman G, Quick KL, Dugan LL. Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. Science. 2007 Dec 12/7/2007; 318(5856): 1645-7. PMID: 18063801, PII: 318/5856/1645, DOI: 10.1126/science.1148045, ISSN: 1095-9203.

Ali SS, Xiong C, Lucero J, Behrens MM, Dugan LL, Quick KL. Gender differences in free radical homeostasis during aging: shorter-lived female C57BL6 mice have increased oxidative stress. Aging Cell. 2006 Dec; 5(6): 565-74. PMID: 17129217, PII: ACE252, DOI: 10.1111/j.1474-9726.2006.00252.x, ISSN: 1474-9718.

Kim-Han JS, Kopp SJ, Dugan LL, Diringer MN. Perihematomal mitochondrial dysfunction after intracerebral hemorrhage. Stroke [print-electronic]. 2006 Oct; 37(10): 2457-62. PMID: 16960094, PII: 01.STR.0000240674.99945.4e, DOI: 10.1161/01.STR.0000240674.99945.4e, ISSN: 1524-4628.

Kim-Han JS, Dugan LL. Mitochondrial uncoupling proteins in the central nervous system. Antioxid. Redox Signal. 2005 Sep; 7(9-10): 1173-81. PMID: 16115020, DOI: 10.1089/ars.2005.7.1173, ISSN: 1523-0864.

Dugan LL, Quick KL. Reactive oxygen species and aging: evolving questions. Sci Aging Knowledge Environ. 2005 Jun 6/29/2005; 2005(26): pe20. PMID: 15994214, PII: 2005/26/pe20, DOI: 10.1126/sageke.2005.26.pe20, ISSN: 1539-6150.

Cuddihy SL, Musiek ES, Morrow JD, Dugan LL. Long-term vitamin E deficiency in mice decreases superoxide radical production in brain. Ann. N. Y. Acad. Sci. 2004 Dec; 1031: 428-31. PMID: 15753188, PII: 1031/1/428, DOI: 10.1196/annals.1331.064, ISSN: 0077-8923.

Ali SS, Hardt JI, Quick KL, Kim-Han JS, Erlanger BF, Huang TT, Epstein CJ, Dugan LL. A biologically effective fullerene (C60) derivative with superoxide dismutase mimetic properties. Free Radic. Biol. Med. 2004 Oct 10/15/2004; 37(8): 1191-202. PMID: 15451059, PII: S0891-5849(04)00541-6, DOI: 10.1016/j.freeradbiomed.2004.07.002, ISSN: 0891-5849.

Dugan LL, Kim-Han JS. Astrocyte mitochondria in in vitro models of ischemia. J. Bioenerg. Biomembr. 2004 Aug; 36(4): 317-21. PMID: 15377865, PII: 490848, DOI: 10.1023/B:JOBB.0000041761.61554.44, ISSN: 0145-479X.

Dasgupta B, Dugan LL, Gutmann DH. The neurofibromatosis 1 gene product neurofibromin regulates pituitary adenylate cyclase-activating polypeptide-mediated signaling in astrocytes. J. Neurosci. 2003 Oct 10/1/2003; 23(26): 8949-54. PMID: 14523097, PII: 23/26/8949, ISSN: 1529-2401.

de Erausquin GA, Hyrc K, Dorsey DA, Mamah D, Dokucu M, Mascó DH, Walton T, Dikranian K, Soriano M, García Verdugo JM, Goldberg MP, Dugan LL. Nuclear translocation of nuclear transcription factor-kappa B by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons. Mol. Pharmacol. 2003 Apr; 63(4): 784-90. PMID: 12644578, ISSN: 0026-895X.

Sheline CT, Choi EH, Kim-Han JS, Dugan LL, Choi DW. Cofactors of mitochondrial enzymes attenuate copper-induced death in vitro and in vivo. Ann. Neurol. 2002 Aug; 52(2): 195-204. PMID: 12210790, DOI: 10.1002/ana.10276, ISSN: 0364-5134.

Xia S, Cai ZY, Thio LL, Kim-Han JS, Dugan LL, Covey DF, Rothman SM. The estrogen receptor is not essential for all estrogen neuroprotection: new evidence from a new analog. Neurobiol. Dis. 2002 Apr; 9(3): 282-93. PMID: 11950274, PII: S096999610290478X, DOI: 10.1006/nbdi.2002.0478, ISSN: 0969-9961.

Kim-Han JS, Reichert SA, Quick KL, Dugan LL. BMCP1: a mitochondrial uncoupling protein in neurons which regulates mitochondrial function and oxidant production. J. Neurochem. 2001 Nov; 79(3): 658-68. PMID: 11701769, ISSN: 0022-3042.

Reichert SA, Kim-Han JS, Dugan LL. The mitochondrial permeability transition pore and nitric oxide synthase mediate early mitochondrial depolarization in astrocytes during oxygen-glucose deprivation. J. Neurosci. 2001 Sep 9/1/2001; 21(17): 6608-16. PMID: 11517250, PII: 21/17/6608, ISSN: 1529-2401.

Dugan LL, Lovett EG, Quick KL, Lotharius J, Lin TT, O'Malley KL. Fullerene-based antioxidants and neurodegenerative disorders. Parkinsonism Relat. Disord. 2001 Jul; 7(3): 243-6. PMID: 11331193, PII: S1353-8020(00)00064-X, ISSN: 1873-5126.

Quick KL, Dugan LL. Superoxide stress identifies neurons at risk in a model of ataxia-telangiectasia. Ann. Neurol. 2001 May; 49(5): 627-35. PMID: 11357953, ISSN: 0364-5134.

Han BH, DeMattos RB, Dugan LL, Kim-Han JS, Brendza RP, Fryer JD, Kierson M, Cirrito J, Quick K, Harmony JA, Aronow BJ, Holtzman DM. Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia. Nat. Med. 2001 Mar; 7(3): 338-43. PMID: 11231633, PII: 85487, DOI: 10.1038/85487, ISSN: 1078-8956.

Lobner D, Canzoniero LM, Manzerra P, Gottron F, Ying H, Knudson M, Tian M, Dugan LL, Kerchner GA, Sheline CT, Korsmeyer SJ, Choi DW. Zinc-induced neuronal death in cortical neurons. Cell. Mol. Biol. (Noisy-le-grand). 2000 Jun; 46(4): 797-806. PMID: 10875441, ISSN: 0145-5680.

Quick KL, Hardt JI, Dugan LL. Rapid microplate assay for superoxide scavenging efficiency. J. Neurosci. Methods. 2000 Apr 4/15/2000; 97(2): 139-44. PMID: 10788668, PII: S0165027000001795, ISSN: 0165-0270.

Dugan LL, Kim JS, Zhang Y, Bart RD, Sun Y, Holtzman DM, Gutmann DH. Differential effects of cAMP in neurons and astrocytes. Role of B-raf. J. Biol. Chem. 1999 Sep 9/3/1999; 274(36): 25842-8. PMID: 10464325, ISSN: 0021-9258.

Ohlemiller KK, Wright JS, Dugan LL. Early elevation of cochlear reactive oxygen species following noise exposure. Audiol. Neurootol. 1999 Sep; 4(5): 229-36. PMID: 10436315, PII: 13846, DOI: 13846, ISSN: 1420-3030.

Ohlemiller KK, Dugan LL. Elevation of reactive oxygen species following ischemia-reperfusion in mouse cochlea observed in vivo. Audiol. Neurootol. 1999 Sep; 4(5): 219-28. PMID: 10436314, PII: 13845, DOI: 13845, ISSN: 1420-3030.

Behrens MM, Strasser U, Lobner D, Dugan LL. Neurotrophin-mediated potentiation of neuronal injury. Microsc. Res. Tech. 1999 May 5/15/1999; 45(4-5): 276-84. PMID: 10383120, PII: 10.1002/(SICI)1097-0029(19990515/01)45:4/5<276::AID-JEMT11>3.0.CO;2-4, DOI: 10.1002/(SICI)1097-0029(19990515/01)45:4/5<276::AID-JEMT11>3.0.CO;2-4, ISSN: 1059-910X.

Lotharius J, Dugan LL, O'Malley KL. Distinct mechanisms underlie neurotoxin-mediated cell death in cultured dopaminergic neurons. J. Neurosci. 1999 Feb 2/15/1999; 19(4): 1284-93. PMID: 9952406, ISSN: 0270-6474.

Beetsch JW, Park TS, Dugan LL, Shah AR, Gidday JM. Xanthine oxidase-derived superoxide causes reoxygenation injury of ischemic cerebral endothelial cells. Brain Res. 1998 Mar 3/9/1998; 786(1-2): 89-95. PMID: 9554965, PII: S0006-8993(97)01407-8, ISSN: 0006-8993.

Yu SP, Yeh CH, Sensi SL, Gwag BJ, Canzoniero LM, Farhangrazi ZS, Ying HS, Tian M, Dugan LL, Choi DW. Mediation of neuronal apoptosis by enhancement of outward potassium current. Science. 1997 Oct 10/3/1997; 278(5335): 114-7. PMID: 9311914, ISSN: 0036-8075.

Dugan LL, Turetsky DM, Du C, Lobner D, Wheeler M, Almli CR, Shen CK, Luh TY, Choi DW, Lin TS. Carboxyfullerenes as neuroprotective agents. Proc. Natl. Acad. Sci. U.S.A. 1997 Aug 8/19/1997; 94(17): 9434-9. PMID: 9256500, PMCID: PMC23208, ISSN: 0027-8424.

Hsu CY, Shaikh A, Yeh CH, Dugan LL, Lin TS, Xu J. Enhancement of apoptosis in cerebral endothelial cells by selected inflammatory signals. Ann. N. Y. Acad. Sci. 1997 Aug 8/14/1997; 823: 148-53. PMID: 9292041, ISSN: 0077-8923.

Dugan LL, Creedon DJ, Johnson EM, Holtzman DM. Rapid suppression of free radical formation by nerve growth factor involves the mitogen-activated protein kinase pathway. Proc. Natl. Acad. Sci. U.S.A. 1997 Apr 4/15/1997; 94(8): 4086-91. PMID: 9108109, PMCID: PMC20572, ISSN: 0027-8424.

Farhangrazi ZS, Ying H, Bu G, Dugan LL, Fagan AM, Choi DW, Holtzman DM. High density lipoprotein decreases beta-amyloid toxicity in cortical cell culture. Neuroreport. 1997 Mar 3/24/1997; 8(5): 1127-30. PMID: 9175098, ISSN: 0959-4965.

Papadopoulos MC, Koumenis IL, Dugan LL, Giffard RG. Vulnerability to glucose deprivation injury correlates with glutathione levels in astrocytes. Brain Res. 1997 Feb 2/14/1997; 748(1-2): 151-6. PMID: 9067456, PII: S0006-8993(96)01293-0, ISSN: 0006-8993.

Goldberg MP, Strasser U, Dugan LL. Techniques for assessing neuroprotective drugs in vitro. Int. Rev. Neurobiol. 1997; 40: 69-93. PMID: 8989617, ISSN: 0074-7742.

Klomp LW, Farhangrazi ZS, Dugan LL, Gitlin JD. Ceruloplasmin gene expression in the murine central nervous system. J. Clin. Invest. 1996 Jul 7/1/1996; 98(1): 207-15. PMID: 8690795, PMCID: PMC507418, DOI: 10.1172/JCI118768, ISSN: 0021-9738.

Dugan LL, Gabrielsen JK, Yu SP, Lin TS, Choi DW. Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. Neurobiol. Dis. 1996 Apr; 3(2): 129-35. PMID: 9173920, PII: S0969-9961(96)90013-3, DOI: 10.1006/nbdi.1996.0013, ISSN: 0969-9961.

Gwag BJ, Koh JY, Chen MM, Dugan LL, Behrens MM, Lobner D, Choi DW. BDNF or IGF-I potentiates free radical-mediated injury in cortical cell cultures. Neuroreport. 1995 Dec 12/29/1995; 7(1): 93-6. PMID: 8742425, ISSN: 0959-4965.

Dugan LL, Sensi SL, Canzoniero LM, Handran SD, Rothman SM, Lin TS, Goldberg MP, Choi DW. Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate. J. Neurosci. 1995 Oct; 15(10): 6377-88. PMID: 7472402, ISSN: 0270-6474.

Dugan LL, Lin TS, He YY, Hsu CY, Choi DW. Detection of free radicals by microdialysis/spin trapping EPR following focal cerebral ischemia-reperfusion and a cautionary note on the stability of 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Free Radic. Res. 1995 Jul; 23(1): 27-32. PMID: 7647917, ISSN: 1071-5762.

Dugan LL, Bruno VM, Amagasu SM, Giffard RG. Glia modulate the response of murine cortical neurons to excitotoxicity: glia exacerbate AMPA neurotoxicity. J. Neurosci. 1995 Jun; 15(6): 4545-55. PMID: 7540679, ISSN: 0270-6474.

Bruno VM, Goldberg MP, Dugan LL, Giffard RG, Choi DW. Neuroprotective effect of hypothermia in cortical cultures exposed to oxygen-glucose deprivation or excitatory amino acids. J. Neurochem. 1994 Oct; 63(4): 1398-406. PMID: 7523591, ISSN: 0022-3042.

Anderson DK, Dugan LL, Means ED, Horrocks LA. Methylprednisolone and membrane properties of primary cultures of mouse spinal cord. Brain Res. 1994 Feb 2/21/1994; 637(1-2): 119-25. PMID: 7514081, PII: 0006-8993(94)91224-6, ISSN: 0006-8993.

Dugan LL, Choi DW. Excitotoxicity, free radicals, and cell membrane changes. Ann. Neurol. 1994; 35 Suppl: S17-21. PMID: 8185290, ISSN: 0364-5134.

Monyer H, Giffard RG, Hartley DM, Dugan LL, Goldberg MP, Choi DW. Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin. Neuron. 1992 May; 8(5): 967-73. PMID: 1350203, PII: 0896-6273(92)90211-U, ISSN: 0896-6273.

Saunders RD, Dugan LL, Demediuk P, Means ED, Horrocks LA, Anderson DK. Effects of methylprednisolone and the combination of alpha-tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue. J. Neurochem. 1987 Jul; 49(1): 24-31. PMID: 3108455, ISSN: 0022-3042.

Dugan LL, Demediuk P, Pendley CE, Horrocks LA. Separation of phospholipids by high-performance liquid chromatography: all major classes, including ethanolamine and choline plasmalogens, and most minor classes, including lysophosphatidylethanolamine. J. Chromatogr. 1986 Jun 6/13/1986; 378(2): 317-27. PMID: 3733991.

Anderson DK, Demediuk P, Saunders RD, Dugan LL, Means ED, Horrocks LA. Spinal cord injury and protection. Ann Emerg Med. 1985 Aug; 14(8): 816-21. PMID: 3927795, PII: S0196-0644(85)80064-0, ISSN: 0196-0644.

Anderson DK, Saunders RD, Demediuk P, Dugan LL, Braughler JM, Hall ED, Means ED, Horrocks LA. Lipid hydrolysis and peroxidation in injured spinal cord: partial protection with methylprednisolone or vitamin E and selenium. Cent Nerv Syst Trauma. 1985; 2(4): 257-67. PMID: 3836012, ISSN: 0737-5999.