BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Laura L. Dugan
Associate Professor, Geriatric Medicine, UCSD
eRA COMMONS USER NAME
ladugan
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Massachusetts Institute of Technology
The Ohio State Univ. College of Medicine
A.
DEGREE
(if applicable)
YEAR(s)
SB
MD
1977-1981
1981-1987
FIELD OF STUDY
Biology (Course VII)
Medicine
Positions and Honors. List in chronological order previous positions, concluding with your present position. List any honors. Include
present membership on any Federal Government public advisory committee.
Professional Experience:
1987-1990 Residency in Internal Medicine, Dept. of Medicine, Children’s Hospital, UCSF, San Francisco, CA.
1989-1990 Chief Resident, Internal Medicine, Children’s Hospital, UCSF, San Francisco.
1990-1992 Fellowship in Geriatric Medicine, Stanford University Medical School, Stanford, CA.
1992-1993 Dana Research Fellowship, Geriatric Medicine, Stanford Medical School.
1993-1995 Instructor, Departments of Neurology and Medicine, Washington Univ. Med. School, St. Louis, MO.
1995-2002 Assistant Professor, Departments of Neurology and Medicine, Washington Univ. Med. School
2002-2005 Associate Professor with tenure, Depts. of Neurology and Medicine, Washington Univ. Med. School
2005Associate Professor and Hillblom Chair in Geriatric Medicine, University of California, San Diego
2007Head, Division of Geriatric Medicine, UCSD
Honors and Awards:
1977
United States Presidential Scholar (Awarded by President Jimmy Carter, Washington DC, 6/77)
1977
National Merit Scholar
1977
Bausch and Lomb Science Award
1982-1984 Roessler Research Scholarship, The Ohio State University College of Medicine.
1984-1986 NIH Pre-doctoral Fellowship
1992
Hartford Foundation Award in Geriatrics
1993
Kopolow Award for Geriatric Psychiatry and Neurology
1998
Paul Beeson Physician Scholars in Aging Research Award
1999
St. Louis Academy of Sciences Innovation Award
2003
Scientific Advisor to regional 1st Place, Nat’l 2nd place team in Toshiba ExploraVision Competition
2005-2007 John A. Hartford Geriatrics Leadership Scholar Award
B.
Selected peer-reviewed publications (in chronological order). Do not include publications submitted or in preparation (40 of 46).
1. Dugan LL, Demediuk P, Pendley II CE and Horrocks LA. (1986) Separation of phospholipids by HPLC: All
major classes, including ethanolamine and choline plasmalogens, and most minor classes, including
lysophosphatidylethanolamine. J. Chromatogr. 378:317-327.
2. Saunders RD, Dugan LL, Demediuk P, Means ED, Anderson DK and Horrocks LA. (1987) Effects of
methylprednisolone and the combination of alpha-tocopherol and selenium on arachidonic acid metabolism
and lipid peroxidation in traumatized spinal tissue. J. Neurochem. 49:24-31.
3. Monyer H, Giffard RG, Hartley DM, Dugan LL, Goldberg MP and Choi DW. (1992) Oxygen or glucose
deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin. Neuron 8:967-973.
4. Anderson DK, Dugan LL, Means ED, and Horrocks LA. (1994) Methylprednisolone and membrane
properties of primary cultures of mouse spinal cord. Brain Res., 637:119-125.
5. Bruno VMG, Goldberg MP, Dugan LL, Giffard RG and Choi DW. (1994) The effect of hypothermia on
oxygen-glucose deprivation and excitatory amino acid induced injury in cortical cultures. J. Neurochem.
63:1398-1406.
6. Dugan LL, Lin TT, He YY, Hsu CY and Choi DW. (1995) Detection of free radicals by microdialysis/spin
trapping EPR following focal cerebral ischemia-reperfusion and a cautionary note on the stability of 5, 5dimethyl-1-pyrroline N-oxide (DMPO). Free Rad. Res., 23:27-32.
7. Dugan LL, Bruno VMG, Amagasu SM, and Giffard RG. (1995) Glia modulate the response of murine
cortical neurons to excitotoxicity: glia exacerbate AMPA neurotoxicity. J. Neurosci., 15:4545-4555.
8. Dugan LL, Sensi SL, Canzoniero LMT, Handran SD, Rothman SM, Lin TT, Goldberg MP, and Choi DW.
(1995) Mitochondrial production of reactive oxygen species in cortical neurons following exposure to Nmethyl-D-aspartate. J. Neurosci., 15:6377-6388.
9. Gwag BJ, Koh JY, Chen MM, Dugan LL, Behrens M, Lobner, D, and Choi DW. (1995) BDNF or IGF-I
potentiates radical mediated injury in cortical cell cultures. NeuroReport, 7:93-96.
10. Dugan LL, Gabrielsen JK,Yu SP, Lin, TS, and Choi DW. (1996) Buckminsterfullerenol free radical
scavengers reduce excitotoxic and apoptotic death of cultured cortical neurons. Neurobiol. Dis. 3:129-135.
11. Klomp LWJ, Farhangrazi S, Dugan LL, and Gitlin JD. (1996) Ceruloplasmin gene expression in the murine
central nervous system. J. Clin. Invest. 98:207-215.
12. Farhangrazi ZS, Ying H, Bu G, Dugan LL, Fagan AM, Choi DW, and Holtzman DM. (1997) High density
lipoprotein decreases beta-amyloid toxicity in cortical cell culture. Neuroreport 8:1127-1130.
13. Papadopoulos MC, Koumenis IL, Dugan LL, and Giffard RG. (1997) Vulnerability to glucose deprivation
injury correlates with glutathione levels in astrocytes. Brain Res. 748:151-156.
14. Goldberg MP, Strasser U, and Dugan LL. (1997) Techniques for assessing neuroprotective drugs in vitro.
Int. Rev. Neurobiol. 40:60-93
15. Dugan LL, Creedon DJ, Johnson EM, and Holtzman DM. (1997) Rapid suppression of free radical
formation by NGF involves the MAPK pathway. Proc. Natl. Acad. Sci. U.S.A. 94:4086-4091.
16. Dugan LL, Turetsky DM, Du C, Lobner D, Wheeler M, Almli R, Shen CKF, Luh TY, Choi, DW and Lin TS.
(1997) Carboxyfullerenes as Neuroprotective Agents. Proc. Natl. Acad. Sci. U.S.A. 94:9434-9439.
17. Yu SP, Yeh CH, Sensi SL, Gwag BJ, Canzoniero LMT, Farhangrazi ZS, Ying HS, Tian M, Dugan LL and
Choi DW. (1997) Mediation of neuronal apoptosis by enhancement of outward potassium current. Science
278:114-117.
18. Hsu CY, Shaikh A, Yeh CH, Dugan LL, Lin TS, Xu J. (1997) Enhancement of apoptosis in cerebral
endothelial cells by selected inflammatory signals. Ann. N. Y. Acad. Sci. 823:148-153.
19. Beetsch JW, Park TS, Dugan LL, Shah AR, and Gidday JM. (1998) Xanthine oxidase-derived superoxide
causes reoxygenation injury of ischemic cerebral endothelial cells. Brain Res.786:89-95.
20. Ohlemiller KK, Wright JS, and Dugan LL. (1999) Early elevation of cochlear reactive oxygen species
following noise exposure. Audiol. Neuro-Otol 4:229-36.
21. Ohlemiller KK, and Dugan LL. (1999) Elevation of reactive oxygen species following ischemia-reperfusion
in mouse cochlea observed In vivo. Audiol. Neuro-Otol. 4:219-28.
22. Lotharius J, Dugan LL, and O’Malley KL. (1999) Distinct mechanisms underlie neurotoxin-mediated cell
death in cultured dopaminergic neurons. J. Neurosci.19:1284-93.
23. Dugan LL, Kim JS, Zhang Y, Bart RD, Sun Y, Holtzman DM, Gutmann DH. (1999) Differential effects of
cAMP in neurons and astrocytes: Role of B-Raf. J. Biol. Chem. 274:25842-25848.
24. Quick KL, Hardt JI, Dugan LL. (2000) Rapid microplate assay for superoxide scavenging efficiency. J.
Neurosci. Methods 97:139-144.
25. Lobner D, Canzoniero LM, Manzerra P, Gottron F, Ying H, Knudson M, Tian M, Dugan LL, Kerchner GA,
Sheline CT, Korsmeyer SJ, Choi DW. (2000) Zinc-induced neuronal death in cortical neurons. Cell Mol.
Biol. 46:797-806.
26. Han BH, DeMattos RB, Dugan LL, Kim-Han JS, Brendza R, Fryer JD, Kierson M, Cirrito J, Quick K,
Harmony J, Aronow B, Holtzman DM. (2001) Clusterin/apolipoprotein J deficient mice: Decreased brain
injury via a caspase-3 independent pathway in a model of cerebral palsy. Nat. Med., 7:338-343.
27. Quick KL and Dugan LL. (2001) Superoxide stress identifies neurons at-risk in a model of ataxiatelangiectasia. Ann. Neurol. 49:627-635.
28. Reichert SA, Kim-Han JS, Dugan LL. (2001) the mitochondrial permeability transition and nitric oxide
synthase mediate early mitochondrial depolarization in astrocytes during oxygen-glucose deprivation. J.
Neurosci., 21:6608-16.
29. Kim-Han JS, Reichert SA, Dugan LL. (2001) BMCP1: a mitochondrial uncoupling protein in neurons which
regulates mitochondrial function and oxidant production. J. Neurochem., 79:658-668.
30. Xia S, Cai ZY, Thio LL, Kim-Han JS, Dugan LL, Covey DF, Rothman SM. (2002) the estrogen receptor is
not essential for all estrogen neuroprotection: new evidence from a new analog. Neurobiol. Dis. 9: 282-293.
31. Sheline CT, Choi EH, Kim-Han JS, Dugan LL, Choi DW. (2002) Co-factors of mitochondrial enzymes
attenuate copper-induced neuronal death in vitro and in vivo. Ann. Neurol. 52:195-204.
32. De Erasquin GA, Hyrc K, Dorsey DA, Mamah D, Dokucu M, Masco DH, Walton T, Dikranian K, Soriano M,
Verdugo JMG, Goldberg MP, Dugan LL. (2003) Nuclear translocation of nuclear transcription factor-B by
-amino-3-hydroxy-5-methyl-4-isozolepropionic acid receptors leads to transcription of p53 and cell death
in dopaminergic neurons. Mol. Pharmacol. 63:784-90.
33. Dasgupta B, Dugan LL, Gutmann DH. (2003) the neurofibromatosis 1 (NF1) gene product regulates
PACAP-mediated signaling in astrocytes. J. Neurosci. 23:8949-54.
34. Cuddihy SL, Musiek ES, Morrow, JD, Dugan LL. (2004) Long-term vitamin E deficiency in mice decreases
superoxide radical production in brain. Ann. N.Y. Acad. Sci. 1031:428-31.
35. Ali SS, Hardt JI, Quick KL, Kim-Han JS, Erlanger BF, Huang T-T, Epstein CJ, Dugan LL. (2004) A
biologically effective fullerene (C60) derivative with superoxide dismutase mimetic properties. Free Rad.
Biol. Med. 37:1191-202.
36. Dugan LL, and Quick KL. (2005) Reactive oxygen species and aging: evolving questions. Sci. Aging
Knowledge Environ. 26:pe20.
37. Kim-Han JS, and Dugan LL. (2005) Mitochondrial uncoupling proteins in the central nervous system.
Antiox. Redox Signal., 7:1173-81.
38. Kim-Han, JS, Kopp, SA, Dugan, LL*, Diringer, MN. (2006) Peri-hematomal mitochondrial dysfunction
following intracerebral hemorrhage. Stroke 37:2457-2462. *Corresponding author.
39. Quick, KL, Ali, SS, Arch, R, Xiong, C, Wozniak, D, Dugan, LL. (2006) A carboxyfullerene SOD mimetic
improves cognition and extends the lifespan of mice. Neurobiology of Aging, E-Pub 9/06, Print 29:117-28
(2008).
40. Ali, SS, Xiong, C, Lucero, J, Behrens, MM, Dugan, LL*, Quick, KL. (2006) Gender differences in free
radical homeostasis during aging: Shorter-lived female C57BL6 mice have increased oxidative stress.
Aging Cell. 5:565-74. *Corresponding author.
41. Behrens, MM, Ali, SS, Dao, DN, Lucero, J, Shekhtman, G, Quick, KL, Dugan, LL (2007) Ketamine-induced
loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase Science 318:1645-7.
42. Cuddihy, SL, Ali, SS, Musiek, E, Lucero, J, Kopp, S, Morrow, J, Dugan, LL. (2008) Prolonged -tocopherol
deficiency decreases oxidative stress and unmasks -tocopherol-dependent regulation of mitochondrial
function in brain. J. Biol. Chem. 283:6915-24.
43. Ali, SS, Hardt, JI, Dugan, LL. (2008) SOD activity of carboxyfullerenes predicts their neuroprotective
efficacy: A structure-activity study. Nanomedicine, In press.
44. Behrens, MM, Ali, SS, Dugan, LL. (2008) Interleukin-6 mediates the increase in NADPH-oxidase in the
ketamine model of schizophrenia. Journal of Neuroscience, submitted
C. Research Support. List selected ongoing or completed (during the last three years) research projects (federal and non-federal support).
Begin with the projects that are most relevant to the research proposed in this application. Briefly indicate the overall goals of the projects and
your role (e.g. PI, Co-Investigator, Consultant) in the research project. Do not list award amounts or percent effort in projects.
Ongoing Research Support:
Hartford Foundation Beeson
Scholars Collaborative Projects Award
Dugan (PI-UCSD), J. Walston (PI- JHU)
8/15/07-8/14/09
Cross-institution collaborative project to explore role of inflammation in frailty. Walston group to study role of
peripheral inflammation in the frailty phenotype, and Dugan group to study how peripheral inflammation
induces CNS inflammation, and how this relates to increased vulnerability to delirium and cognitive decline
during aging.
Larry L. Hillblom Network Grant on Aging
Dugan, PI
1/1/08 – 12/31/12
Mapping the Redox Neurobiology of Aging Interdisciplinary network grant to carry out spatial and temporal
studies to “map” changes in redox biology in nervous system aging using molecular, fluorescence imaging,
novel PET and MRI technologies, and translational approaches.
1R21AG030320-01
Dugan, PI
9/1/07-8/30/10
NIA Improved Spin Probes for Magnetic Resonance Imaging of Oxygen and Reactive Oxygen Species
This R21 proposes to develop the spin probe, N@C3, for Overhauser-enhanced MRI imaging of oxygen
radical species in vivo. Studies will use N@C3 provided by Mike Alford (collaborator at TDA, Ltd).
Larry L. Hillblom Network Grant
Lithgow, PI; Dugan, Co-Investigator
1/1/07-12/31/10
Chemical Biology of Aging. Explores the genetic basis of the anti-aging effects of fullerene-based antioxidants
in C. elegans and Drosophila.
1R41AG029707–01(STTR)
M. Alford, PI; Dugan, Co-Investigator
8/1/07 -7/31/08
Development of Improved Spin Probes for Aging Research (subcontract to Dugan through TDA)
The aim of this Phase I STTR is to determine the optimal approach needed to synthesize highly-enriched
N@C3. TDA synthesize the derivative, N@C3, and the Dugan lab will screen various lots of compound.
RO1 NS50425-01A1
Perlmutter, PI; Dugan, Co-Investigator
NINDS (subcontract to Dugan through Washington University in St. Louis)
Carboxyfullerene treatment of MPTP-induced Parkinsonism
2/28/07-3/31/10
5RO1NS036226505
Goldberg, PI; Dugan, Co-Investigator
9/10/97-7/31/08
NINDS (subcontract to Dugan through Washington University in St. Louis)
Oligodendrocyte Death in Cerebral Ischemia. The goal of this project is to examine the vulnerability of
oligodendrocytes to excitotoxic injury.
Selma I. Hartke Bequest for Aging Research
Dugan, PI
Open period
K25 Mentored Scientist Award, NIA. Detection of Intracellular Oxygen Species (Ali, PI; Dugan, Mentor).
RO1 NIA
Lithgow, PI; Dugan, Co-I
12/1/07 – 11/30/12
Pharmacology of Lifespan Extension (subcontract to Dugan through the Buck Institute)
Project uses compounds which extend lifespan of C. elegans to probe aging pathways. Dugan lab will prepare
and characterize several fullerene antioxidant compounds with selected antioxidant and biophysical properties
to help probe the role and sources of ROS in aging and lifespan.
Completed (last 3 years):
RO1 NS49176-01
Dugan, PI
060/1/01 – 05/31/06
UCP5: Balancing Metabolism and Oxidative Stress in Aging Brain. Investigates the role of mitochondrial
uncoupling protein-5 on energy metabolism, free radical production, and development of age-associated
neurodegenerative disorders.
Department of Defense, Concept Award
Dugan, PI
06/01/07 – 05/31/08
Cognitive Deficits in NF1 reflect abnormal synaptic plasticity due to increased reactive oxygen species
generation. This project will study Erk signaling-dependent regulation of reactive oxygen species as a critical
cause of impaired learning in NF1 children using a mouse model of NF1
Pending
R01 AG033679-01
Dugan, PI
04/01/09 – 03/31/14
NIA/NIH
Systemic Inflammation and Central Nervous System Dysfunction: A Mechanistic and translational Study
Experiments in our proposal fall into the categories of basic and translational neuroscience, but the results of
our work should have very practical and relatively immediate implications for our understanding not only of
brain aging, but the role of systemic inflammatory pathways in normal nervous system function, as well as
aging.
R01
Dugan, PI
04/01/09 – 03/31/14
NIH/NIMH
NADPH-Oxidase and dysfunction of inhibitory interneurons critical to psychosis
Our proposal is based on our findings that induction of NADPH oxidase through the pro-inflammatory cytokine
IL-6 leads to dysfunction of a key population of inhibitory neurons that are known to be critical to memory
encoding, and which are highly vulnerable in schizophrenia, drug-induced psychosis, and age-related cognitive
impairment.