Department / Division:
Medicine / Neurology

Address:
DUMC 2900
Durham, NC 27710

Appointment Telephone:
919-684-7246

Office Telephone:
919-684-0056

Fax Telephone:
919-684-6514

• MD, Duke University School of Medicine, 1991

• Neurology, University of Pennsylvania, 1991-1995
• Cerebrovascular Disease and Neurocritical Care, Duke University Medical Center, 1995-1997
• Board Certifications, 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.  In both cell culture systems and animal models, our primary focus is on examining the role of oxidative stress 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 Neurocritial 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.

Representative Publications:
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. (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 CNS inflammatory response. J Biol Chem. 2003 Sep 24. (2003) 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(2):437-45. (2003) 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 Dec;33(12):2950-6. (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 Nov;51(5):1128-34; discussion 1134-5. (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. Ann Neurol. 2002 Jan;51(1):113-7. (2002) Abstract

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. (2002) 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. J Leukoc Biol. 2001 Oct;70(4):677-83. (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. J Neuroimmunol. 2001 Mar 1;114(1-2):107-13. (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. Exp Neurol. 2001 Jan;167(1):74-85. (2001) 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. J Thorac Cardiovasc Surg. 2001 Sep;122(3):622-3. (2001) Abstract

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. (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 May 11;99(18):2371-7. (1999) 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. J Cereb Blood Flow Metab. 1998 Apr;18(4):361-6. (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 Mar 9;9(4):615-8. (1998) Abstract

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. (1998) Abstract

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. (1997) Abstract

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. (1997) Abstract