Daniel Todd Laskowitz

Laskowitz

Professor of Neurology

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 have recently translated a novel apoE mimetic from the preclinical setting to a multi center Phase 2 trial evaluating efficacy in intracranial hemorrhage. 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.

Appointments and Affiliations

  • Professor of Neurology
  • Assistant Dean for Scholarly Education
  • Director, Duke Clinical Research Institute in the Department of Neurology
  • Vice Chair for Academic Affairs in the Department of Neurology
  • Professor in Neurosurgery
  • Professor in Neurobiology
  • Professor in Anesthesiology
  • Associate of the Duke Initiative for Science & Society
  • Memeber in the Duke Clinical Research Institute
  • Affiliate, Duke Global Health Institute

Contact Information

  • Office Location: 227B Bryan Res Bldg, Durham, NC 27710
  • Office Phone: +1 919 684 0056
  • Email Address: daniel.laskowitz@duke.edu

Education

  • Duke University, 1997
  • University of Pennsylvania, 1995
  • M.D. Duke University, 1991

Awards, Honors, and Distinctions

  • A.A. Bennet Award in Neuroscience. Brown University . 2017
  • Chairman Award for Excellence. Duke University Medical Center. 2017
  • Faculty inductee, AOA Medical Honor Society. AOA. 2011
  • Annual Scientific Award, Society of Critical Care Medicine. SCCM. 2010
  • Fellow, American Neurological Association. ANA. 2003
  • Fellow, American Heart Association. AHA. 2001
  • Paul Beeson Physician Faculty Scholar. American Foundation Aging Research. 1999
  • Upjohn and Pharmacia Award for Outstanding CNS Research. Upjohn and Pharmacia/ Duke University Medical Center. 1997
  • Genentech Young Investigator Award in Stroke. AAN/Genentech. 1997
  • National Stroke Association Fellowship. National Stroke Association . 1997
  • American Association of Neurology Resident Scholar Award. University of Pennsylvania. 1995
  • Long Island Jewish Medical Center Intern of the Year. Long Island Jewish Medical Center. 1992
  • Sandoz Award for Superior Academic Achievement. Duke University School of Medicine. 1991

Courses Taught

  • THESIS 301B: Thesis
  • INTERDIS 312B: Research Ethics
  • CRS 301B: CONTINUATION OF RESEARCH STUDY

In the News

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., J Emerg Med, vol 42 no. 1 (2012), pp. 40-43 [10.1016/j.jemermed.2008.06.028] [abs].
  • James, ML; Blessing, R; Phillips-Bute, BG; Bennett, E; Laskowitz, DT, S100B and brain natriuretic peptide predict functional neurological outcome after intracerebral haemorrhage., Biomarkers, vol 14 no. 6 (2009), pp. 388-394 [10.1080/13547500903015784] [abs].
  • 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, vol 40 no. 3 (2009), pp. 880-887 [10.1161/STROKEAHA.108.531236] [abs].
  • James, ML; Sullivan, PM; Lascola, CD; Vitek, MP; Laskowitz, DT, Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage., Stroke, vol 40 no. 2 (2009), pp. 632-639 [10.1161/STROKEAHA.108.530402] [abs].
  • 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, vol 35 no. 2 (2009), pp. 329-338 [10.1016/j.ultrasmedbio.2008.08.016] [abs].
  • 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, vol 37 no. 1 (2009), pp. 38-45 [10.1177/0310057X0903700111] [abs].
  • 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, vol 18 no. 2 (2009), pp. 144-149 [10.1016/j.jstrokecerebrovasdis.2008.09.012] [abs].
  • 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, vol 40 no. 1 (2009), pp. 77-85 [10.1161/STROKEAHA.108.516377] [abs].
  • Takata, K; Sheng, H; Borel, CO; Laskowitz, DT; Warner, DS; Lombard, FW, Long-term cognitive dysfunction following experimental subarachnoid hemorrhage: new perspectives., Exp Neurol, vol 213 no. 2 (2008), pp. 336-344 [10.1016/j.expneurol.2008.06.009] [abs].
  • 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, vol 34 no. 9 (2008), pp. 1387-1395 [10.1016/j.ultrasmedbio.2008.01.015] [abs].
  • Gump, W; Laskowitz, DT, Management of post-subarachnoid hemorrhage vasospasm., Curr Atheroscler Rep, vol 10 no. 4 (2008), pp. 354-360 [10.1007/s11883-008-0054-7] [abs].
  • Laskowitz, DT; Warner, DS, The use of S100B as a biomarker in subarachnoid hemorrhage: clarity in its promise and limits., Crit Care Med, vol 36 no. 8 (2008), pp. 2452-2453 [10.1097/CCM.0b013e3181810457] [abs].
  • 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, vol 51 no. 6 (2008), pp. 775-780.e3 [10.1016/j.annemergmed.2007.11.002] [abs].
  • Laskowitz, DT; Warner, DS, Statins in acute brain injury: getting the cart before the horse., Neurocrit Care, vol 8 no. 1 (2008), pp. 3-5 [10.1007/s12028-007-9040-0] [abs].
  • James, ML; Warner, DS; Laskowitz, DT, Preclinical models of intracerebral hemorrhage: a translational perspective., Neurocrit Care, vol 9 no. 1 (2008), pp. 139-152 [10.1007/s12028-007-9030-2] [abs].
  • Laskowitz, DT; Vitek, MP, Apolipoprotein E and neurological disease: therapeutic potential and pharmacogenomic interactions., Pharmacogenomics, vol 8 no. 8 (2007), pp. 959-969 [10.2217/14622416.8.8.959] [abs].
  • Wang, H; Lynch, JR; Song, P; Yang, H-J; 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, vol 206 no. 1 (2007), pp. 59-69 [10.1016/j.expneurol.2007.03.031] [abs].
  • 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, vol 24 no. 7 (2007), pp. 1093-1107 [10.1089/neu.2006.0192] [abs].
  • Mace, BE; Wang, H; Lynch, JR; Moss, J; Sullivan, P; Colton, H; Morgan, K; Renauld, J-C; Laskowitz, DT, Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway., Neurol Res, vol 29 no. 3 (2007), pp. 243-250 [10.1179/016164107X158974] [abs].
  • 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, vol 144 no. 4 (2007), pp. 1324-1333 [10.1016/j.neuroscience.2006.11.017] [abs].
  • Ely, EW; Girard, TD; Shintani, AK; Jackson, JC; Gordon, SM; Thomason, JWW; 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, vol 35 no. 1 (2007), pp. 112-117 [10.1097/01.CCM.0000251925.18961.CA] [abs].
  • Jauch, EC; Laskowitz, DT, Can D-dimer levels identify patients at risk for early neurological deterioration in acute ischemic stroke?, Nat Clin Pract Neurol, vol 2 no. 11 (2006), pp. 590-591 [10.1038/ncpneuro0321] [abs].
  • 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, vol 105 no. 5 (2006), pp. 671-674 [10.3171/jns.2006.105.5.671] [abs].
  • 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, vol 21 no. 3 (2006) [10.3171/foc.2006.21.3.4] [abs].
  • Li, F-Q; 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, vol 318 no. 3 (2006), pp. 956-965 [10.1124/jpet.106.103671] [abs].
  • 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, vol 368 no. 9536 (2006), pp. 694-703 [10.1016/S0140-6736(06)69254-4] [abs].
  • Warner, DS; Laskowitz, DT, Changing outcome from aneurysmal subarachnoid hemorrhage: another step closer., Anesthesiology, vol 104 no. 4 (2006), pp. 629-630 [10.1097/00000542-200604000-00002] [abs].
  • 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, vol 531 no. 1-3 (2006), pp. 126-132 [10.1016/j.ejphar.2005.12.031] [abs].
  • 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, vol 185 (2006), pp. 15-20 [10.1111/j.1600-0404.2006.00680.x] [abs].
  • 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, vol 4 no. 1 (2006), pp. 25-31 [10.1385/NCC:4:1:025] [abs].
  • 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, vol 68 no. 3 (2006), pp. 369-375 [10.1097/01.psy.0000221272.77984.e2] [abs].
  • 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, vol 5 no. 1 (2006), pp. 71-78 [10.1385/NCC:5:1:71] [abs].
  • 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., Crit Care Med, vol 33 no. 11 (2005), pp. 2521-2526 [10.1097/01.ccm.0000186368.96146.fb] [abs].
  • 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, vol 36 no. 9 (2005), pp. 2024-2026 [10.1161/01.STR.0000177879.11607.10] [abs].
  • Laskowitz, DT; Blessing, R; Floyd, J; White, WD; Lynch, JR, Panel of biomarkers predicts stroke., Ann N Y Acad Sci, vol 1053 (2005) [10.1196/annals.1344.051] [abs].
  • 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, vol 192 no. 1 (2005), pp. 109-116 [10.1016/j.expneurol.2004.11.014] [abs].
  • 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, vol 52 (2005), pp. 371-378 [abs].
  • Lynch, JR; Blessing, R; White, WD; Grocott, HP; Newman, MF; Laskowitz, DT, Novel diagnostic test for acute stroke., Stroke, vol 35 no. 1 (2004), pp. 57-63 [10.1161/01.STR.0000105927.62344.4C] [abs].
  • 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., J Biol Chem, vol 278 no. 49 (2003), pp. 48529-48533 [10.1074/jbc.M306923200] [abs].
  • 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, vol 98 no. 6 (2003), pp. 1222-1226 [10.3171/jns.2003.98.6.1222] [abs].
  • 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, vol 116 no. 2 (2003), pp. 437-445 [10.1016/s0306-4522(02)00709-1] [abs].
  • 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, vol 33 no. 12 (2002), pp. 2950-2956 [10.1161/01.str.0000038986.68044.39] [abs].
  • 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, vol 51 no. 5 (2002), pp. 1128-1134 [10.1097/00006123-200211000-00005] [abs].
  • Aono, M; Lee, Y; Grant, ER; Zivin, RA; Pearlstein, RD; Warner, DS; Bennett, ER; Laskowitz, DT, Apolipoprotein E protects against NMDA excitotoxicity., Neurobiol Dis, vol 11 no. 1 (2002), pp. 214-220 [10.1006/nbdi.2002.0541] [abs].
  • 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, vol 51 no. 1 (2002), pp. 113-117 [10.1002/ana.10098] [abs].
  • 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, vol 70 no. 4 (2001), pp. 677-683 [abs].
  • 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, vol 122 no. 3 (2001), pp. 622-623 [10.1067/mtc.2001.115152] [abs].
  • 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, vol 114 no. 1-2 (2001), pp. 107-113 [10.1016/s0165-5728(00)00459-8] [abs].
  • 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, vol 167 no. 1 (2001), pp. 74-85 [10.1006/exnr.2001.7541] [abs].
  • Laskowitz, DT; Lee, DM; Schmechel, D; Staats, HF, Altered immune responses in apolipoprotein E-deficient mice., J Lipid Res, vol 41 no. 4 (2000), pp. 613-620 [abs].
  • 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, vol 99 no. 18 (1999), pp. 2371-2377 [10.1161/01.cir.99.18.2371] [abs].
  • Laskowitz, DT; Horsburgh, K; Roses, AD, Apolipoprotein E and the CNS response to injury., J Cereb Blood Flow Metab, vol 18 no. 5 (1998), pp. 465-471 [10.1097/00004647-199805000-00001] [abs].
  • 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, vol 18 no. 4 (1998), pp. 361-366 [10.1097/00004647-199804000-00003] [abs].
  • 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, vol 9 no. 4 (1998), pp. 615-618 [10.1097/00001756-199803090-00010] [abs].
  • 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, vol 17 no. 7 (1997), pp. 753-758 [10.1097/00004647-199707000-00005] [abs].
  • Laskowitz, DT; Goel, S; Bennett, ER; Matthew, WD, Apolipoprotein E suppresses glial cell secretion of TNF alpha., J Neuroimmunol, vol 76 no. 1-2 (1997), pp. 70-74 [10.1016/s0165-5728(97)00021-0] [abs].