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Laurie Kilpatrick, PhD
Associate Professor, Physiology
Associate Professor, Sol Sherry Thrombosis Research Center
Telephone: 215-707-8420
Email: laurie.kilpatrick@temple.edu
Department of Physiology
BA, Hampshire College, Amherst, MA
PhD, Biochemistry, University of Pennsylvania, Philadelphia, PA
Postdoctoral Fellowship, Pharmacology, University of Pennsylvania, Philadelphia, PA
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PROFESSIONAL AFFILIATIONS: |
- Sigma Xi
- American Physiological Society
- Society for Leukocyte Biology
- Shock Society
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My research focuses on investigating mechanisms that control proinflammatory signaling in cells of the innate immune system. A particular focus is neutrophil dysfunction and the development of acute lung injury and Acute Respiratory Distress Syndrome (ARDS). Neutrophils are key components of host defense against infection but, if not appropriately regulated, can also trigger lung injury and the development of ARDS. TNF and other proinflammatory cytokines are implicated in neutrophil dysfunction through activation of inflammatory signaling and suppression of neutrophil spontaneous apoptosis. Understanding the molecular mechanisms regulating neutrophil lifespan and proinflammatory mediator release is critical for development of novel therapies targeting neutrophil dysfunction during inflammation. My laboratory is investigating signaling pathways that control 1) the release of toxic oxygen radicals and proteases, 2) cell survival and apoptosis, and 3) crosstalk between cytokines and β2-integrins in regulating neutrophil cellular responses. Recently, we identified the kinase, delta Protein Kinase C (δ-PKC) as an important regulator of pro-inflammatory and anti-apoptotic signaling in the neutrophil. Control of specific signaling components such as δ-PKC offers a unique site for therapeutic intervention that could protect the lung from neutrophil-mediated tissue damage during inflammatory diseases. We are currently conducting preclinical studies in a rodent model of ARDS to test a novel δ-PKC-TAT inhibitory peptide for the treatment of acute lung injury.
A second area of research is investigating the mechanism of crosstalk between the chemokine receptor CCR5 and the Substance P (SP) receptor neurokinin-1 (NK1R). SP is an important neuroimmune modulator, particularly with respect to the immune functions of monocytes/macrophages. SP is a potent pro-inflammatory mediator and plays an important role in inflammation and viral infections such as HIV infection. The objective of these studies is to determine how SP regulates chemokine signaling and chemotaxis in human monocytes and macrophages.
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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)
19801500. Kilpatrick LE, Sun S, Li H, Vary TC, Korchak HM, Regulation of TNF-induced oxygen radical production in human neutrophils: role of {delta}-PKC. J Leukoc Biol :()2009 Oct 2
19427266. Tuluc F, Lai JP, Kilpatrick LE, Evans DL, Douglas SD, Neurokinin 1 receptor isoforms and the control of innate immunity. Trends Immunol 30:6(271-6)2009 Jun
19179340. Meshki J, Douglas SD, Lai JP, Schwartz L, Kilpatrick LE, Tuluc F, Neurokinin 1 receptor mediates membrane blebbing in HEK293 cells through a Rho/Rho-associated coiled-coil kinase-dependent mechanism. J Biol Chem 284:14(9280-9)2009 Apr 3
19076368. Douglas SD, Lai JP, Tuluc F, Schwartz L, Kilpatrick LE, Neurokinin-1 receptor expression and function in human macrophages and brain: perspective on the role in HIV neuropathogenesis. Ann N Y Acad Sci 1144:(90-6)2008 Nov
18835883. Chernova I, Lai JP, Li H, Schwartz L, Tuluc F, Korchak HM, Douglas SD, Kilpatrick LE, Substance P (SP) enhances CCL5-induced chemotaxis and intracellular signaling in human monocytes, which express the truncated neurokinin-1 receptor (NK1R). J Leukoc Biol 85:1(154-64)2009 Jan
18713853. Lai JP, Lai S, Tuluc F, Tansky MF, Kilpatrick LE, Leeman SE, Douglas SD, Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor. Proc Natl Acad Sci U S A 105:34(12605-10)2008 Aug 26
17157935. Korchak HM, Dorsey LB, Li H, Mackie D, Kilpatrick LE, Selective roles for alpha-PKC in positive signaling for O-(2) generation and calcium mobilization but not elastase release in differentiated HL60 cells. Biochim Biophys Acta 1773:3(440-9)2007 Mar
17138860. Kilpatrick LE, Sun S, Mackie D, Baik F, Li H, Korchak HM, Regulation of TNF mediated antiapoptotic signaling in human neutrophils: role of delta-PKC and ERK1/2. J Leukoc Biol 80:6(1512-21)2006 Dec
16675550. Lai JP, Ho WZ, Kilpatrick LE, Wang X, Tuluc F, Korchak HM, Douglas SD, Full-length and truncated neurokinin-1 receptor expression and function during monocyte/macrophage differentiation. Proc Natl Acad Sci U S A 103:20(7771-6)2006 May 16
16227031. Harris MC, D'Angio CT, Gallagher PR, Kaufman D, Evans J, Kilpatrick L, Cytokine elaboration in critically ill infants with bacterial sepsis, necrotizing entercolitis, or sepsis syndrome: correlation with clinical parameters of inflammation and mortality. J Pediatr 147:4(462-8)2005 Oct
12055072. Kilpatrick LE, Lee JY, Haines KM, Campbell DE, Sullivan KE, Korchak HM, A role for PKC-delta and PI 3-kinase in TNF-alpha-mediated antiapoptotic signaling in the human neutrophil. Am J Physiol Cell Physiol 283:1(C48-57)2002 Jul
11443050. Korchak HM, Corkey BE, Yaney GC, Kilpatrick LE, Negative regulation of ligand-initiated Ca(2+) uptake by PKC-beta II in differentiated HL60 cells. Am J Physiol Cell Physiol 281:2(C514-23)2001 Aug
11237707. Korchak HM, Kilpatrick LE, TNFalpha elicits association of PI 3-kinase with the p60TNFR and activation of PI 3-kinase in adherent neutrophils. Biochem Biophys Res Commun 281:3(651-6)2001 Mar 2
11120743. Korchak HM, Kilpatrick LE, Roles for beta II-protein kinase C and RACK1 in positive and negative signaling for superoxide anion generation in differentiated HL60 cells. J Biol Chem 276:12(8910-7)2001 Mar 23
11078718. Kilpatrick LE, Song YH, Rossi MW, Korchak HM, Serine phosphorylation of p60 tumor necrosis factor receptor by PKC-delta in TNF-alpha-activated neutrophils. Am J Physiol Cell Physiol 279:6(C2011-8)2000 Dec
10391855. Kaufman D, Kilpatrick L, Hudson RG, Campbell DE, Kaufman A, Douglas SD, Harris MC, Decreased superoxide production, degranulation, tumor necrosis factor alpha secretion, and CD11b/CD18 receptor expression by adherent monocytes from preterm infants. Clin Diagn Lab Immunol 6:4(525-9)1999 Jul
9765254. Korchak HM, Rossi MW, Kilpatrick LE, Selective role for beta-protein kinase C in signaling for O-2 generation but not degranulation or adherence in differentiated HL60 cells. J Biol Chem 273:42(27292-9)1998 Oct 16
9124510. Thom SR, Mendiguren I, Hardy K, Bolotin T, Fisher D, Nebolon M, Kilpatrick L, Inhibition of human neutrophil beta2-integrin-dependent adherence by hyperbaric O2. Am J Physiol 272:3 Pt 1(C770-7)1997 Mar
8914768. Kobrynski LJ, Tanimune L, Kilpatrick L, Campbell DE, Douglas SD, Production of T-helper cell subsets and cytokines by lymphocytes from patients with chronic mucocutaneous candidiasis. Clin Diagn Lab Immunol 3:6(740-5)1996 Nov
7776086. Dulkerian SJ, Kilpatrick L, Costarino AT Jr, McCawley L, Fein J, Corcoran L, Zirin S, Harris MC, Cytokine elevations in infants with bacterial and aseptic meningitis. J Pediatr 126:6(872-6)1995 Jun
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