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RWJMS Homepage | Department of Surgery Homepage | General Surgery Residency

Stephen F. Lowry, MD &
Steve Calvano, PhD

Division of Surgical Sciences

The main focus of our laboratory is to understand the mechanisms that underlie the systemic inflammatory response that occurs in severely injured patients or those with infections. Approximately fifteen years ago, this laboratory was involved in seminal work that demonstrated that cytokines elaborated from mononuclear phagocytes play a major role in initiating and amplifying the systemic inflammatory response. We continue to investigate the regulation of pro- and anti-inflammatory cytokines and their receptors. Additionally, we have embarked on studies investigating the importance of leukocyte turnover in modulation of the systemic inflammatory response. At the molecular/genetic level we are working to determine the effects of genetic mutations and polymorphisms on the susceptibility and clinical course of patients with systemic inflammation or sepsis. Finally, gene expression array analyses are being used to determine changes in the pattern of gene expression in normal volunteers given a small dose of bacterial endotoxin and patients in the SICU setting.

Our laboratory employs a four-pronged approach using in vitro models, animal models, normal human volunteer studies conducted in the Clinical Research Center and studies of severely-injured ICU patients. This approach facilitates the rapid translation of laboratory and basic science findings to the clinic.

Recent Publications

  • Kotani J, Avallone NJ, Lin E, Goshima M, Gandhi K, Lowry SF, Calvano SE. Fas­mediated neutrophil apoptosis and associated A1 protein expression during systemic inflammation are regulated independently of both tumor necrosis factor receptors. Shock 19:201-207, 2003.
  • Abraham E, Naum C, Bandi V, Gervich D, Lowry SF, Wunderink R, Schein RM, Macias W, Skerjanec S, Dmitrienko A, Farid N, Forgue ST, Jiang F. Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure. Crit Care Med 31:718-728, 2003.
  • Calvano JE, Um JY, Agnese DM, Hahm SJ, Kumar A, Coyle SM, Calvano SE, Lowry SF. Influence of the TNF-a and TNF-b polymorphisms upon infectious risk and outcome in surgical intensive care patients. Surg Infect 4:163-169, 2003.
  • Langenfeld EM, Calvano SE, Lowry SF, Amenta P, Langenfeld J. The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells. Carcinogenesis Jun 19 [Epub ahead of print], 2003.
  • Schuster DP, Metzler M, Opal S, Lowry SF, Balk R, Abraham E, Levy H, Slotman G, Coyne E, Souza S, Pribble J and the Pafase ARDS Prevention Study Group. Recombinant platelet-activating factor acetylhydrolase to prevent acute respiratory distress syndrome and mortality in severe sepsis: A phase Ilb, multicenter randomized, placebo-controlled, clinical trial. Crit Care Med (in press), 2003.
  • Calvano JE, Um JY, Goshima M, Singhal R, Coyle SM, Reddell MT, Kumar A, Bunker KL, Calvano SE, Lowry SF. Modulation of the LPS receptor complex (CD14, TLR4, MD-2) and TLR2 in SIRS positive patients with and without infection: Relationship to tolerance. Shock (in press), 2003.
  • Kotani J, Avallone NJ, Lin E, Goshima M, Gandhi K, Lowry SF, Calvano SE. Fas-mediated neutrophil apoptosis and associated A1 protein expression during systemic inflammation are regulated independently of both tumor necrosis factor receptors. Shock 19:201-207, 2003.
  • Abraham E, Naum C, Bandi V, Gervich D, Lowry SF, Wunderink R, Schein RM, Macias W, Skerjanec S, Dmitrienko A, Farid N, Forgue ST, Jiang F. Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure. Crit Care Med 31:718-728, 2003.
  • Calvano JE, Um JY, Agnese DM, Hahm SJ, Kumar A, Coyle SM, Calvano SE, Lowry SF. Influence of the TNF- and TNF- polymorphisms upon infectious risk and outcome in surgical intensive care patients. Surg Infect 4:163-169, 2003.
  • Langenfeld EM, Calvano SE, Lowry SF, Amenta P, Langenfeld J. The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells. Carcinogenesis 24:1445-1454, 2003.
  • Calvano JE, Agnese DM, Um JY, Goshima M, Singhal R, Coyle SM, Reddell MT, Kumar A, Calvano SE, Lowry SF. Modulation of the lipopolysaccharide receptor complex (CD14, TLR4, MD-2) and toll-like receptor 2 in systemic inflammatory response syndrome-positive patients with and without infection: Relationship to tolerance. Shock 20:415-419, 2003.
  • Schuster DP, Metzler M, Opal S, Lowry SF, Balk R, Abraham E, Levy H, Slotman G, Coyne E, Souza S, Pribble J and the Pafase ARDS Prevention Study Group. Recombinant platelet-activating factor acetylhydrolase to prevent acute respiratory distress syndrome and mortality in severe sepsis: Phase IIb, multicenter randomized, placebo-controlled, clinical trial. Crit Care Med 31:1612-1619, 2003.
  • Kalil AC, Coyle SM, Um JY, LaRosa SP, Turlo MA, Calvano SE, Sundin DP, Nelson DR, Lowry SF. Effects of drotrecogin alfa (activated) in human endotoxemia. Shock 21:222-229, 2004.
  • Opal S, Laterre PF, Abraham E, Francois B, Wittebole X, Lowry SF, Dhainaut JF, Warren B, Dugernier T, Lopez A, Sanchez M, Demeyer I, Jauregui L, Lorente JA, McGee W, Reinhart K, Kljucar S, Souza S, Pribble J, Controlled Mortality Trial of Platelet-Activating Factor Acetylhydrolase in Severe Sepsis Investigators. Recombinant human platelet-activating factor acetylhydrolase for treatment of severe sepsis: results of a phase III, multicenter, randomized, double-blind, placebo-controlled, clinical trial. Crit Care Med 32:332-341, 2004.
  • Barie PS, Williams MD, McCollam JS, Bates BM, Qualy RL, Lowry SF, Fry DE, for the PROWESS Surgical Evaluation Committee. Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with severe sepsis. Am J Surg 188:212-220, 2004.
  • Fry DE, Beilman G, Johnson S, Williams MD, Rodman G, Booth FV, Bates BM, McCollam JS, Lowry SF, for the PROWESS Surgical Evaluation Committee. Safety of Drotrecogin Alfa (activated) in surgical patients with sepsis. Surg Infect 5:253-259, 2004.
  • Lowry SF, Awad S, Ford H, Cheadle W, Williams MD, Qualy RL, McCollam JS, Bates BM, Fry DE, for the PROWESS Surgical Evaluation Committee. Static and dynamic assessment of biomarkers in surgical patients with severe sepsis. Surg Infect 5:261-268, 2004.
  • Copeland S, Warren HS, Lowry SF, Calvano SE, Remick D. Acute inflammatory response to endotoxin in mice and humans. Clin Diagn Lab Immunol 12:60-67, 2005
  • Qian WJ, Jacobs JM, Camp DG, Monroe ME, Moore RJ, Gritsenko MA, Calvano SE, Lowry SF, Xiao W, Moldawer LL, Davis RW, Tompkins RG, Smith RD. Comparative proteome analyses of human plasma following in vivo lipopolysaccharide administration using multidimensional separations coupled with tandem mass spectrometry. Proteomics 5:572-584, 2005
  • Cobb JP, Mindrinos MN, Miller-Graziano C, Calvano SE, Baker HV, Xiao W, Laudanski K, Brownstein BH, Elson CM, Hayden DL, Herndon DN, Lowry SF, Maier RV, Schoenfeld DA, Moldawer LL, Davis RW, Tompkins RG. Application of genome-wide expression analysis to human health and disease. Proc Natl Acad Sci (USA) 102:4801-4806, 2005
  • Qian WJ, Monroe ME, Liu T, Jacobs JM, Anderson GA, Shen Y, Moore RJ, Anderson DJ, Zhang R, Calvano SE, Lowry SF, Xiao W, Moldawer LL, Davis RW, Tompkins RG, Camp DG, Smith RD. Quantitative proteome analysis of human plasma following in vivo lipopolysaccharide administration using 16O/18O labeling and the accurate mass and time tag approach. Mol Cell Proteomics 4:700-709, 2005
  • Wittebole X, Coyle SM, Kumar A, Goshima M, Lowry SF, Calvano SE. Expression of tumour necrosis factor receptor and Toll-like receptor 2 and 4 on peripheral blood leucocytes of human volunteers after endotoxin challenge: a comparison of flow cytometric light scatter and immunofluorescence gating. Clin Exp Immunol 141:99-106, 2005
  • Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke SK, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF. A network-based analysis of systemic inflammation in humans. Nature 437:1032-1037, 13Oct2005

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