Physicians

Departments / Divisions

• Medicine / Medicine-Neurology
• Neurobiology
• Anesthesiology

Address
DUMC 2900
Durham, NC 27710

Appointment Telephone
919-684-7246

Office Telephone
919-684-0056

Fax Telephone
919-684-6514

Training

• MD, Duke University School of Medicine, 1991

Residency

• Neurology, Hospital of the University of Pennsylvania, 1991-1995
• Cerebrovascular Disease and Neurocritical Care, Duke University Medical Center, 1995-1997
• Board-Certified, Neurology and Vascular Neurology

Clinical Interests
Stroke and cerebrovascular disease, neurointensive care and neurological complications of critical illness, general neurology

Research Interests
Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical setting of stroke, intracranial hemorrhage, and closed head injury.

In conjunction with the Multidisciplinary Neuroprotection Laboratories, we also focus on clinically relevant small animal models of acute CNS injury. For example, we have recently characterized murine models of closed head injury, subarachnoid hemorrhage, intracranial hemorrhage and perinatal hypoxia-ischemia, in addition to the standard rodent models of focal stroke and transient forebrain ischemia. Recently we have adapted several of these models from the rat to the mouse to take advantage of murine transgenic technology. The objective of these studies are two-fold: to gain better insight into the cellular responses and pathophysiology of acute brain injury, and to test novel therapeutic strategies for clinical translation. In both cell culture systems and animal models, our primary focus is on examining the role of oxidative stress and inflammatory mechanism in mediating brain injury following acute brain insult, and examining the neuroprotective effects of endogenous apolipoprotein E in the injured mammalian central nervous system.

Our laboratory is committed to translational research, and has several active clinical research protocols, which are designed to bring the research performed in the Multidisciplinary Research Laboratories to the clinical arena. These protocols are centered around patients following stroke and acute brain injury, and are primarily based out of the Emergency Room and Neurocritical Care Unit. For example, we are currently examining the role of inflammatory mediators for use as a point-of-care diagnostic marker following stroke, intracranial hemorrhage, andclosed head injury. We are also examining the functional role of different polymorphisms of of inflammatory cytokines in the setting of acute brain injury and neurological dysfunction following cardiopulmonary bypass.

Industry Relationships and Collaborations (What's this?)

This faculty member (or a member of their immediate family) has a working relationship (i.e. consulting, research, and/or educational services) with the companies listed below. These relations have been reported to the health system leadership and, when appropriate, management plans are in place to address potential conflicts.

• Astute Medical
• Cognosci Inc
• Janssen Pharmaceuticals (Johnson & Johnson)
• NeurOp
• Roche Diagnostics
• TheraSim
• UCB Pharma
• Upsher-Smith Labs

Representative Publications
Phillips, S; Stanley, L; Nicoletto, H; Burkman, M; Laskowitz, DT; Cairns, CB. Use of emergency department transcranial Doppler assessment of reperfusion after intravenous tPA for ischemic stroke. Journal of Emergency Medicine. 2012;42:40-43. (2012) Abstract

James, ML; Blessing, R; Bennett, E; Laskowitz, DT. Apolipoprotein E modifies neurological outcome by affecting cerebral edema but not hematoma size after intracerebral hemorrhage in humans. Journal of Stroke and Cerebrovascular Diseases. 2009;18:144-149. (2009) Abstract

James, ML; Blessing, R; Phillips-Bute, BG; Bennett, E; Laskowitz, DT. S100B and brain natriuretic peptide predict functional neurological outcome after intracerebral haemorrhage. Biomarkers. 2009;14:388-394. (2009) Abstract

James, ML; Sullivan, PM; Lascola, CD; Vitek, MP; Laskowitz, DT. Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage. Stroke. 2009;40:632-639. (2009) Abstract

Laskowitz, DT; Kasner, SE; Saver, J; Remmel, KS; Jauch, EC; BRAIN Study Group. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study. Stroke. 2009;40:77-85. (2009) Abstract

Mathew, JP; Mackensen, GB; Phillips-Bute, B; Grocott, HP; Glower, DD; Laskowitz, DT; Blumenthal, JA; Newman, MF; Neurologic Outcome Research Group (NORG) of the Duke Heart Center. Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine in cardiac surgery. Stroke. 2009;40:880-887. (2009) Abstract

Smith, SW; Ivancevich, NM; Lindsey, BD; Whitman, J; Light, E; Fronheiser, M; Nicoletto, HA; Laskowitz, DT. The ultrasound brain helmet: feasibility study of multiple simultaneous 3D scans of cerebral vasculature. Ultrasound in Medicine and Biology. 2009;35:329-338. (2009) Abstract

Wang, H; Christensen, DJ; Vitek, MP; Sullivan, PM; Laskowitz, DT. APOE genotype affects outcome in a murine model of sepsis: implications for a new treatment strategy. Anaesthesia and Intensive Care. 2009;37:38-45. (2009) Abstract

Glickman, SW; Anstrom, KJ; Lin, L; Chandra, A; Laskowitz, DT; Woods, CW; Freeman, DH; Kraft, M; Beskow, LM; Weinfurt, KP; Schulman, KA; Cairns, CB. Challenges in enrollment of minority, pediatric, and geriatric patients in emergency and acute care clinical research. Annals of Emergency Medicine. 2008;51:775-780.e3. (2008) Abstract

Gump, W; Laskowitz, DT. Management of post-subarachnoid hemorrhage vasospasm. Current Atherosclerosis Reports. 2008;10:354-360. (2008) Abstract

Ivancevich, NM; Pinton, GF; Nicoletto, HA; Bennett, E; Laskowitz, DT; Smith, SW. Real-time 3-D contrast-enhanced transcranial ultrasound and aberration correction. Ultrasound in Medicine and Biology. 2008;34:1387-1395. (2008) Abstract

James, ML; Warner, DS; Laskowitz, DT. Preclinical models of intracerebral hemorrhage: a translational perspective. Neurocritical Care. 2008;9:139-152. (2008) Abstract

Laskowitz, DT; Warner, DS. Statins in acute brain injury: getting the cart before the horse. Neurocritical Care. 2008;8:3-5. (2008) Abstract

Laskowitz, DT; Warner, DS. The use of S100B as a biomarker in subarachnoid hemorrhage: clarity in its promise and limits. Critical Care Medicine. 2008;36:2452-2453. (2008) Abstract

Takata, K; Sheng, H; Borel, CO; Laskowitz, DT; Warner, DS; Lombard, FW. Long-term cognitive dysfunction following experimental subarachnoid hemorrhage: new perspectives. Experimental Neurology. 2008;213:336-344. (2008) Abstract

Ely, EW; Girard, TD; Shintani, AK; Jackson, JC; Gordon, SM; Thomason, JW; Pun, BT; Canonico, AE; Light, RW; Pandharipande, P; Laskowitz, DT. Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients. Critical Care Medicine. 2007;35:112-117. (2007) Abstract

Laskowitz, DT; McKenna, SE; Song, P; Wang, H; Durham, L; Yeung, N; Christensen, D; Vitek, MP. COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury. Journal of Neurotrauma. 2007;24:1093-1107. (2007) Abstract

Laskowitz, DT; Vitek, MP. Apolipoprotein E and neurological disease: therapeutic potential and pharmacogenomic interactions. Pharmacogenomics. 2007;8:959-969. (2007) Abstract

Mace, BE; Wang, H; Lynch, JR; Moss, J; Sullivan, P; Colton, H; Morgan, K; Renauld, JC; Laskowitz, DT. Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway. Neurological Research. 2007;29:243-250. (2007) Abstract

Wang, H; Durham, L; Dawson, H; Song, P; Warner, DS; Sullivan, PM; Vitek, MP; Laskowitz, DT. An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction. Neuroscience. 2007;144:1324-1333. (2007) Abstract

Wang, H; Lynch, JR; Song, P; Yang, HJ; Yates, RB; Mace, B; Warner, DS; Guyton, JR; Laskowitz, DT. Simvastatin and atorvastatin improve behavioral outcome, reduce hippocampal degeneration, and improve cerebral blood flow after experimental traumatic brain injury. Experimental Neurology. 2007;206:59-69. (2007) Abstract

Gao, J; Wang, H; Sheng, H; Lynch, JR; Warner, DS; Durham, L; Vitek, MP; Laskowitz, DT. A novel apoE-derived therapeutic reduces vasospasm and improves outcome in a murine model of subarachnoid hemorrhage. Neurocritical Care. 2006;4:25-31. (2006) Abstract

Jauch, EC; Laskowitz, DT. Can D-dimer levels identify patients at risk for early neurological deterioration in acute ischemic stroke?. Nature Reviews: Neurology. 2006;2:590-591. (2006) Abstract

Laskowitz, DT; Fillit, H; Yeung, N; Toku, K; Vitek, MP. Apolipoprotein E-derived peptides reduce CNS inflammation: implications for therapy of neurological disease. Acta Neurologica Scandinavica, Supplement. 2006;185:15-20. (2006) Abstract

Leinenweber, SB; Sheng, H; Lynch, JR; Wang, H; Batini¿-Haberle, I; Laskowitz, DT; Crapo, JD; Pearlstein, RD; Warner, DS. Effects of a manganese (III) porphyrin catalytic antioxidant in a mouse closed head injury model. European Journal of Pharmacology. 2006;531:126-132. (2006) Abstract

Li, FQ; Sempowski, GD; McKenna, SE; Laskowitz, DT; Colton, CA; Vitek, MP. Apolipoprotein E-derived peptides ameliorate clinical disability and inflammatory infiltrates into the spinal cord in a murine model of multiple sclerosis. Journal of Pharmacology and Experimental Therapeutics. 2006;318:956-965. (2006) Abstract

McGirt, MJ; Blessing, R; Alexander, MJ; Nimjee, SM; Woodworth, GF; Friedman, AH; Graffagnino, C; Laskowitz, DT; Lynch, JR. Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: A multivariate analysis of an institutional experience. Journal of Neurosurgery. 2006;105:671-674. (2006) Abstract

Mesis, RG; Wang, H; Lombard, FW; Yates, R; Vitek, MP; Borel, CO; Warner, DS; Laskowitz, DT. Dissociation between vasospasm and functional improvement in a murine model of subarachnoid hemorrhage. Neurosurgical Focus. 2006;21:E4. (2006) Abstract

Newman, MF; Mathew, JP; Grocott, HP; Mackensen, GB; Monk, T; Welsh-Bohmer, KA; Blumenthal, JA; Laskowitz, DT; Mark, DB. Central nervous system injury associated with cardiac surgery. Lancet. 2006;368:694-703. (2006) Abstract

Phillips-Bute, B; Mathew, JP; Blumenthal, JA; Grocott, HP; Laskowitz, DT; Jones, RH; Mark, DB; Newman, MF. Association of neurocognitive function and quality of life 1 year after coronary artery bypass graft (CABG) surgery. Psychosomatic Medicine. 2006;68:369-375. (2006) Abstract

Wang, H; Gao, J; Lassiter, TF; McDonagh, DL; Sheng, H; Warner, DS; Lynch, JR; Laskowitz, DT. Levetiracetam is neuroprotective in murine models of closed head injury and subarachnoid hemorrhage. Neurocritical Care. 2006;5:71-78. (2006) Abstract

Warner, DS; Laskowitz, DT. Changing outcome from aneurysmal subarachnoid hemorrhage: another step closer. Anesthesiology. 2006;104:629-630. (2006) Abstract

Laskowitz, DT; Blessing, R; Floyd, J; White, WD; Lynch, JR. Panel of biomarkers predicts stroke. Annals of the New York Academy of Sciences. 2005;1053:30. (2005) Abstract

Lynch, JR; Wang, H; Mace, B; Leinenweber, S; Warner, DS; Bennett, ER; Vitek, MP; McKenna, S; Laskowitz, DT. A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury. Experimental Neurology. 2005;192:109-116. (2005) Abstract

Lynch, JR; Wang, H; McGirt, MJ; Floyd, J; Friedman, AH; Coon, AL; Blessing, R; Alexander, MJ; Graffagnino, C; Warner, DS; Laskowitz, DT. Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke. 2005;36:2024-2026. (2005) Abstract

McGirt, MJ; Woodworth, GF; Pradilla, G; Legnani, F; Warner, D; Tamargo, R; Clatterbuck, R; Lynch, JR; Laskowitz, DT. Galbraith Award: simvastatin attenuates experimental cerebral vasospasm and ameliorates serum markers of neuronal and endothelial injury in patients after subarachnoid hemorrhage: a dose-response effect dependent on endothelial nitric oxide synthase. Clinical neurosurgery. 2005;52:371-378. (2005) Abstract

Moretti, EW; Morris, RW; Podgoreanu, M; Schwinn, DA; Newman, MF; Bennett, E; Moulin, VG; Mba, UU; Laskowitz, DT; Perioperative Genetics and Safety Outcomes Study (PEGASUS) Investigative Team. APOE polymorphism is associated with risk of severe sepsis in surgical patients. Critical Care Medicine. 2005;33:2521-2526. (2005) Abstract

Lynch, JR; Blessing, R; White, WD; Grocott, HP; Newman, MF; Laskowitz, DT. Novel diagnostic test for acute stroke. Stroke. 2004;35:57-63. (2004) Abstract

Aono, M; Bennett, ER; Kim, KS; Lynch, JR; Myers, J; Pearlstein, RD; Warner, DS; Laskowitz, DT. Protective effect of apolipoprotein E-mimetic peptides on N-methyl-D-aspartate excitotoxicity in primary rat neuronal-glial cell cultures. Neuroscience. 2003;116:437-445. (2003) Abstract

Lynch, JR; Tang, W; Wang, H; Vitek, MP; Bennett, ER; Sullivan, PM; Warner, DS; Laskowitz, DT. APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response. Journal of Biological Chemistry. 2003;278:48529-48533. (2003) Abstract

McGirt, MJ; Mavropoulos, JC; McGirt, LY; Alexander, MJ; Friedman, AH; Laskowitz, DT; Lynch, JR. Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Journal of Neurosurgery. 2003;98:1222-1226. (2003) Abstract

Aono, M; Lee, Y; Grant, ER; Zivin, RA; Pearlstein, RD; Warner, DS; Bennett, ER; Laskowitz, DT. Apolipoprotein E protects against NMDA excitotoxicity. Neurobiology of Disease. 2002;11:214-220. (2002) Abstract

Lynch, JR; Pineda, JA; Morgan, D; Zhang, L; Warner, DS; Benveniste, H; Laskowitz, DT. Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema. Annals of Neurology. 2002;51:113-117. (2002) Abstract

McGirt, MJ; Lynch, JR; Blessing, R; Warner, DS; Friedman, AH; Laskowitz, DT. Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2002;51:1128-1134. (2002) Abstract

McGirt, MJ; Lynch, JR; Parra, A; Sheng, H; Pearlstein, RD; Laskowitz, DT; Pelligrino, DA; Warner, DS. Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke. 2002;33:2950-2956. (2002) Abstract

Grocott, HP; Newman, MF; El-Moalem, H; Bainbridge, D; Butler, A; Laskowitz, DT. Apolipoprotein E genotype differentially influences the proinflammatory and anti-inflammatory response to cardiopulmonary bypass. Journal of Thoracic and Cardiovascular Surgery. 2001;122:622-623. (2001) Abstract

Laskowitz, DT; Thekdi, AD; Thekdi, SD; Han, SK; Myers, JK; Pizzo, SV; Bennett, ER. Downregulation of microglial activation by apolipoprotein E and apoE-mimetic peptides. Experimental Neurology. 2001;167:74-85. (2001) Abstract

Lynch, JR; Morgan, D; Mance, J; Matthew, WD; Laskowitz, DT. Apolipoprotein E modulates glial activation and the endogenous central nervous system inflammatory response. Journal of Neuroimmunology. 2001;114:107-113. (2001) Abstract

Misra, UK; Adlakha, CL; Gawdi, G; McMillian, MK; Pizzo, SV; Laskowitz, DT. Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages. Journal of Leukocyte Biology. 2001;70:677-683. (2001) Abstract

Laskowitz, DT; Lee, DM; Schmechel, D; Staats, HF. Altered immune responses in apolipoprotein E-deficient mice. Journal of Lipid Research. 2000;41:613-620. (2000) Abstract

Mahaffey, KW; Harrington, RA; Simoons, ML; Granger, CB; Graffagnino, C; Alberts, MJ; Laskowitz, DT; Miller, JM; Sloan, MA; Berdan, LG; MacAulay, CM; Lincoff, AM; Deckers, J; Topol, EJ; Califf, RM. Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators. Circulation. 1999;99:2371-2377. (1999) Abstract

Laskowitz, DT; Horsburgh, K; Roses, AD. Apolipoprotein E and the CNS response to injury. Journal of Cerebral Blood Flow and Metabolism. 1998;18:465-471. (1998) Abstract

Laskowitz, DT; Matthew, WD; Bennett, ER; Schmechel, D; Herbstreith, MH; Goel, S; McMillian, MK. Endogenous apolipoprotein E suppresses LPS-stimulated microglial nitric oxide production. Neuroreport. 1998;9:615-618. (1998) Abstract

Sheng, H; Laskowitz, DT; Bennett, E; Schmechel, DE; Bart, RD; Saunders, AM; Pearlstein, RD; Roses, AD; Warner, DS. Apolipoprotein E isoform-specific differences in outcome from focal ischemia in transgenic mice. Journal of Cerebral Blood Flow and Metabolism. 1998;18:361-366. (1998) Abstract

Laskowitz, DT; Goel, S; Bennett, ER; Matthew, WD. Apolipoprotein E suppresses glial cell secretion of TNF alpha. Journal of Neuroimmunology. 1997;76:70-74. (1997) Abstract

Laskowitz, DT; Sheng, H; Bart, RD; Joyner, KA; Roses, AD; Warner, DS. Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral ischemia. Journal of Cerebral Blood Flow and Metabolism. 1997;17:753-758. (1997) Abstract