Associate Professor of Medicine
Duke Department of Medicine, Division of Neurology
Associate Professor of Anesthesiology and Neurobiology
Director, Neurovascular Laboratories
Duke University Medical Center
Durham, NC 27710
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, and closed 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.
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. J Stroke Cerebrovasc Dis. 2009 Mar-Apr;18(2):144-9.
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 Sep;14(6):388-94.
James ML, Sullivan PM, Lascola CD, Vitek MP, Laskowitz DT. Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage. Stroke. 2009 Feb;40(2):632-9.
Laskowitz DT, Kasner SE, Saver J, Remmel KS, Jauch EC. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study. Stroke. 2009 Jan;40(1):77-85.
Mathew JP, Mackensen GB, Phillips-Bute B, Grocott HP, Glower DD, Laskowitz DT, Blumenthal JA, Newman MF. Randomized, double-blinded, placebo controlled study of neuroprotection with lidocaine in cardiac surgery. Stroke. 2009 Mar;40(3):880-7.
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 Med Biol. 2009 Feb;35(2):329-38.
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. Anaesth Intensive Care. 2009 Jan;37(1):38-45.
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. Ann Emerg Med. 2008 Jun;51(6):775-780.e3.
Gump W, Laskowitz DT. Management of post-subarachnoid hemorrhage vasospasm. Curr Atheroscler Rep. 2008 Aug;10(4):354-60.
Ivancevich NM, Pinton GF, Nicoletto HA, Bennett E, Laskowitz DT, Smith SW. Real-time 3-D contrast-enhanced transcranial ultrasound and aberration correction. Ultrasound Med Biol. 2008 Sep;34(9):1387-95.
James ML, Warner DS, Laskowitz DT. Preclinical models of intracerebral hemorrhage: a translational perspective. Neurocrit Care. 2008;9(1):139-52.
Laskowitz DT, Warner DS. Statins in acute brain injury: getting the cart before the horse. Neurocrit Care. 2008;8(1):3-5.
Laskowitz DT, Warner DS. The use of S100B as a biomarker in subarachnoid hemorrhage: clarity in its promise and limits. Crit Care Med. 2008 Aug;36(8):2452-3.
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. J Emerg Med. 2008 Dec 24.
Takata K, Sheng H, Borel CO, Laskowitz DT, Warner DS, Lombard FW. Long-term cognitive dysfunction following experimental subarachnoid hemorrhage: new perspectives. Exp Neurol. 2008 Oct;213(2):336-44.
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. Crit Care Med. 2007 Jan;35(1):112-7.
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. J Neurotrauma. 2007 Jul;24(7):1093-107.
Laskowitz DT, Vitek MP. Apolipoprotein E and neurological disease: therapeutic potential and pharmacogenomic interactions. Pharmacogenomics. 2007 Aug;8(8):959-69.
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. Neurol Res. 2007 Apr;29(3):243-50.
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 Feb 23;144(4):1324-33.
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. Exp Neurol. 2007 Jul;206(1):59-69.
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. Neurocrit Care. 2006;4(1):25-31.
Jauch EC, Laskowitz DT. Can D-dimer levels identify patients at risk for early neurological deterioration in acute ischemic stroke? Nat Clin Pract Neurol. 2006 Nov;2(11):590-1.
Laskowitz DT, Fillit H, Yeung N, Toku K, Vitek MP. Apolipoprotein E-derived peptides reduce CNS inflammation: implications for therapy of neurological disease. Acta Neurol Scand Suppl. 2006;185:15-20.
Leinenweber SB, Sheng H, Lynch JR, Wang H, Batinić-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. Eur J Pharmacol. 2006 Feb 15;531(1-3):126-32.
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. J Pharmacol Exp Ther. 2006 Sep;318(3):956-65.
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. J Neurosurg. 2006 Nov;105(5):671-4.
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. Neurosurg Focus. 2006;21(3):E4.
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 Aug 19;368(9536):694-703.
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. Psychosom Med. 2006 May-Jun;68(3):369-75.
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. Neurocrit Care. 2006;5(1):71-8.
Warner DS, Laskowitz DT. Changing outcome from aneurysmal subarachnoid hemorrhage: another step closer. Anesthesiology. 2006 Apr;104(4):629-30.
Laskowitz DT, Blessing R, Floyd J, White WD, Lynch JR. Panel of biomarkers predicts stroke. Ann N Y Acad Sci. 2005 Aug;1053:30.
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. Exp Neurol. 2005 Mar;192(1):109-16.
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 Sep;36(9):2024-6.
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. Clin Neurosurg. 2005;52:371-8.
Moretti EW, Morris RW, Podgoreanu M, Schwinn DA, Newman MF, Bennett E, Moulin VG, Mba UU, Laskowitz DT. APOE polymorphism is associated with risk of severe sepsis in surgical patients. Crit Care Med. 2005 Nov;33(11):2521-6.
Lynch JR, Blessing R, White WD, Grocott HP, Newman MF, Laskowitz DT. Novel diagnostic test for acute stroke. Stroke. 2004 Jan;35(1):57-63.
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(2):437-45.
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 CNS inflammatory response. J Biol Chem. 2003 Sep 24.
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. J Neurosurg. 2003 Jun;98(6):1222-6.
Aono M, Lee Y, Grant ER, Zivin RA, Pearlstein RD, Warner DS, Bennett ER, Laskowitz DT. Apolipoprotein E protects against NMDA excitotoxicity. Neurobiol Dis. 2002 Oct;11(1):214-20.
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. Ann Neurol. 2002 Jan;51(1):113-7.
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 Nov;51(5):1128-34; discussion 1134-5.
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 Dec;33(12):2950-6.
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. J Thorac Cardiovasc Surg. 2001 Sep;122(3):622-3.
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. Exp Neurol. 2001 Jan;167(1):74-85.
Lynch JR, Morgan D, Mance J, Matthew WD, Laskowitz DT. Apolipoprotein E modulates glial activation and the endogenous central nervous system inflammatory response. J Neuroimmunol. 2001 Mar 1;114(1-2):107-13.
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. J Leukoc Biol. 2001 Oct;70(4):677-83.
Laskowitz DT, Lee DM, Schmechel D, Staats HF. Altered immune responses in apolipoprotein E-deficient mice. J Lipid Res. 2000 Apr;41(4):613-20.
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 May 11;99(18):2371-7.
Laskowitz DT, Horsburgh K, Roses AD. Apolipoprotein E and the CNS response to injury. J Cereb Blood Flow Metab. 1998 May;18(5):465-71.
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 Mar 9;9(4):615-8.
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. J Cereb Blood Flow Metab. 1998 Apr;18(4):361-6.
Laskowitz DT, Goel S, Bennett ER, Matthew WD. Apolipoprotein E suppresses glial cell secretion of TNF alpha. J Neuroimmunol. 1997 Jun;76(1-2):70-4.
Laskowitz DT, Sheng H, Bart RD, Joyner KA, Roses AD, Warner DS. Apolipoprotein E-deficient mice have increased susceptibility to focal cerebral ischemia. J Cereb Blood Flow Metab. 1997 Jul;17(7):753-8.