Laboratory of Medicinal Biochemistry
Christine Metz, PhD |
The Feinstein Institute for Medical Research
350 Community Drive, 4th Floor
Tel: 516-562-3403
Fax: 516-562-1022
Education:
B.S. 1986 Cornell University
M.S. 1988 Cornell University
Ph.D. 1993 New York University, Sackler Institute of Graduate Biomedical Studies
Appointments:
Research Director of Research, Department of Ob-GYN, Maternal Fetal Medicine Fellowship Program
Associate Professor, Elmezzi Graduate School of Molecular Medicine
Research Summary:
Endothelial cells line the body’s blood vessels to create ‘slippery tubes’ which facilitate the rapid transport of blood throughout the body. Almost every inflammatory condition is associated with tissue damage caused by excessive and/or sustained endothelial cell activation and immune cell infiltration. Because most inflammatory diseases involve endothelial cells, the endothelium is a critical target for anti-inflammation strategies. Dr. Metz’s work focuses on the regulation of inflammation, with an emphasis on endothelial cell activation and immune cell trafficking. More specifically, the laboratory is investigating how the cholinergic anti-inflammatory pathway controls endothelial cell activation and immune cell recruitment to prevent organ injury (e.g. kidney, lung, brain) during inflammation, sepsis, and ischemia-reperfusion injury. Using several experimental models of inflammation, along with both cellular and molecular approaches, the lab is beginning to unravel how cholinergic agonists and anti-inflammatory mediators regulate endothelial cell and immune cell responses.
In addition, Dr. Metz oversees the discovery and development of novel diagnostics and therapeutics for human disease by collaborating with clinicians throughout the North Shore-LIJ Health System. Dr. Metz is the Co-Director of the Tissue Donation Program, which provides valuable human specimens for translational disease-oriented research. As Director of Research for the Maternal Fetal Medicine (MFM) Fellowship Program, Dr. Metz collaborates with Drs. Burton Rochelson, MD and Dawnette Lewis, MD in the Department of Obstetrics-Gynecology (Division of MFM) and the MFM Fellows on research studies using cell-based and experimental models of pre-term labor and pre-eclampsia, inflammatory conditions of pregnancy. Other collaborations within the Health System include: Drs. Barbara Sherry, PhD, Peter Gregersen, MD, and John Lovecchio, MD (Department of Obstetrics and Gynecology) to study early disease markers and genetic risk factors for ovarian cancer; and The Center for Tobacco Control to investigate the effects of smoking cessation on inflammatory responses and to develop improved smoking cessation programs.
Cholinergic regulation of endothelial cell activation in inflammation and sepsis
Sepsis, a leading complication of surgery and trauma, is a condition characterized by a systemic inflammatory response (with excessive cytokine production) associated with infection. Despite numerous advances for the treatment of sepsis, the mortality rate for septic patients is between 20-60%, depending on the severity of their condition. Using experimental models of inflammation and sepsis, we are examining the effects of cholinergic stimulation (through electrical stimulation of the vagus nerve or cholinergic agonists or drugs) on endothelial cell activation and leukocyte trafficking. The endothelium is an important target of anti-inflammation and anti-sepsis strategies (Tracey and Metz, The Comprehensive Treatise on the Endothelium, 2007). The cholinergic anti-inflammatory pathway, originally described by Dr. Kevin Tracey at the Feinstein Institute, is a physiological mechanism that inhibits cytokine production during inflammatory conditions, including sepsis. Electrical stimulation of the efferent vagus nerve, the longest nerve in the body which innervates the heart, stomach, liver, and kidneys, releases the neurotransmitter acetylcholine. Acetylcholine binds to nicotinic acetylcholine receptors present on macrophages and other cells to suppress cytokine production during inflammation (Metz and Tracey, Nature 2005). Likewise, several cholinergic agonists (e.g. nicotine and GTS-21) can bind to nicotinic acetylcholine receptors to dampen inflammation. Initial studies by our laboratory revealed that both vagus nerve stimulation and cholinergic agonists (which bind to nicotinic receptors) suppress endothelial cell activation in vitro and in vivo and block leukocyte trafficking during acute inflammation Saeed et al, JEM 2005). In addition to employing experimental models to study the cholinergic regulation of endothelial cell activation, chemokine production, and leukocyte accumulation in various organs (including the brain, kidney, and lungs), we use human endothelial cell cultures to explore how cholinergic agonists control endothelial cell activation and chemokine production. Current studies focus on the NFκB and STAT3 inflammatory pathways. Interestingly, nicotine exhibits anti-depressant activity. Therefore, we are also interested in investigating how cholinergic agonists and anti-depressants regulate endothelial cell activation and inflammatory responses during depression. Our ongoing studies are expected to improve the understanding of how cholinergic signaling controls endothelial cell activation and leukocyte trafficking in vivo. This work has been funded, in part, by NIH-NIGMS.
Regulation of Kidney Ischemia-Reperfusion Injury by Cholinergic Agonists
Kidney ischemia reperfusion injury is a leading cause of acute renal failure. The incidence of acute renal failure is increasing. Acute renal failure is common in patients after trauma, hemorrhagic shock, cardiopulmonary bypass surgery, and sepsis. The mortality rate for patients with both acute renal failure and sepsis can be as high as 70%. Currently, there are no therapeutic agents for preventing or treating acute renal failure. Using experimental models of renal ischemia-reperfusion injury, we explored the potential role of cholinergic agonists (e.g. nicotine and GTS-21) in protecting against renal ischemia-reperfusion injury. The advantage of this therapeutic strategy is that it targets numerous inflammatory pathways simultaneously. In collaboration with NSUH Pathologists, Drs. Myron Sussin, MD (retired) and Douglas Charney, MD, we have shown that administration of cholinergic agonists suppress ischemia-induced kidney tissue damage (Yeboah et al, Kidney Int’l 2008). Our laboratory has characterized the expression of nicotinic acetylcholine receptors, targets of anti-inflammatory cholinergic agonists, within the kidney under normal conditions and following ischemia-reperfusion injury (Yeboah et al, Am J Physiol Renal Physiol 2008). Our data suggest that cholinergic agonists exert anti-inflammatory effects within the kidney. Current studies are investigating the effects of cholinergic agonist administration on chronic renal damage following ischemia-reperfusion injury, including proteinuria, renal T lymphocyte and macrophage infiltration, and renal fibrosis. Further ongoing studies are examining the cellular and molecular mechanisms whereby cholinergic agonists protect the kidney from ischemic and inflammatory injury.
The Effects Of Smoking Cessation On Inflammatory Responses
Our laboratory collaborates with the Center for Tobacco Control (part of the North Shore-LIJ Health System) on several projects related to smoking cessation (or quitting smoking). Our primary interest it to examine the effects of nicotinic acetylcholine receptor agonists, including nicotine and varenicline, used for smoking cessation on inflammatory responses. In a pilot study funded by the American Heart Association, we examined the effects of quitting smoking on a panel of circulating inflammatory biomarkers associated with cardiovascular disease in ‘at risk’ women during the smoking cessation process (Reichert et al, Chest 2009). We found significant reductions in several serum inflammatory biomarkers linked to cardiovascular disease over the course of smoking cessation. These observations support the anti-inflammatory role of nicotine. In addition, they suggest that there are rapid and measurable consequences of quitting smoking on inflammatory biomarkers in women at risk for cardiovascular disease. Additional, larger studies including diverse smokers seeking to quit smoking will be required to confirm our results. If confirmed, these changes in ‘measurable milestones’ could serve as motivating factors to assist smokers to quit. In addition, we are collaborating with Dr. Peter Gregersen, MD, to identify potential genes involved in the addiction to cigarettes and the ability (or inability) to quit smoking.
Identification of biomarkers associated with alcohol abuse
Our laboratory is working with Feinstein chemist Yousef Al-Abed, PhD, to develop reliable methods to detect acute and chronic alcohol abuse. Acetaldehye is produced by the body following alcohol intake and we have attempted to generate antibodies specific for biomarkers formed in the presence of acetaldehyde. Ultimately, these antibodies could be used to detect biomarkers of alcohol abuse in the blood following binge drinking or chronic alcohol abuse. This work was funded by NIAAA.
Maternal Fetal Medicine Research Program
Our laboratory collaborates with clinicians and fellows in the Division of Maternal Fetal Medicine (MFM) in the Department of Obstetrics and Gynecology. One project is exploring the anti-inflammatory role of magnesium sulfate, a tocolytic agent used to delay pre-term labor. The precise mechanisms of action of magnesium sulfate in pre-term labor are not completely understood. In collaboration with Dr. Burton Rochelson, MD, we discovered that magnesium sulfate suppressed the activation of human umbilical vein endothelial cells through NFB (Rochelson et al, J Repro Immunol 2007). These unexpected observations have important implications in light of recent studies showing that maternal administration of magnesium sulfate is associated with a reduction in cerebral palsy in preterm babies. Current studies in the laboratory are exploring the potential regulation of maternal and fetal inflammation by magnesium sulfate using in vitro and in vivo models.
Additional studies focus on the modulation of maternal and fetal inflammatory responses associated with pre-eclampsia by the cholinergic anti-inflammatory pathway. Numerous studies show that smoking is protective against pre-eclampsia, a condition characterized by hypertension and proteinuria in the second trimester of pregnancy. Pre-eclampsia, often referred to as the septicemia of pregnancy, is characterized by maternal/placental inflammation and can progress to eclampsia, a potentially deadly condition of pregnancy. While smoking is harmful to both the mother and fetus and should be avoided, based on the anti-inflammatory activities of nicotine (a cholinergic agonist and major component of cigarettes) we hypothesized that nicotine was protective against pre-eclampsia. Our early findings revealed that nicotine and other cholinergic agonists suppress cytokine production by cells isolated from the human placenta through the NFκB pathway (Dowling et al Mol Med 2007). Further studies focus on exploring the regulation of maternal and fetal inflammation by cholinergic stimulation using experimental models of pre-eclampsia and pre-term labor.
Our laboratory continues to collaborate with Dr. Akoum from Laval University to explore the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of endometriosis. In addition, we collaborate with many investigators at The Feinstein on other MIF-related projects (Drs. E. Miller, K. Ojamma, and Y. Al-Abed).
Ovarian Cancer Discovery Program
We are currently developing a collaborative discovery program to identify potential risk factors and early diagnostic markers for ovarian cancer. In conjunction with the Tissue Donation Program, we are collaborating with Drs. Barbara Sherry, PhD, Peter Gregersen, MD, John Lovecchio, MD, and the members of the Department of Gynecology Oncology to collect important biological samples for this program.
Lab Members;
Name: Oonagh Dowling, PhD
Position: Research Scientist
Education: Ph.D. 1998 Dublin City University
Research: Obstetrics and Gynecology-related research; cholinergic anti-inflammatory projects.
E-mail: odowling@nshs.edu
Name: Prodyot Chatterjee, PhD
Position: Research Scientist
Education: Ph.D. 1996 Jadavpur University
Research: Cholinergic regulation of endothelial cell activation and leukocyte recruitment: signaling mechanisms and drug screening studies.
E-mail: pchatter@nshs.edu
Name: Xiangying Xue, MD
Position: Research Associate
Education: M.D. 1983 China Medical University
Research: Biomarkers of alcohol abuse; cholinergic regulation of leukocyte trafficking; the effects of depression and smoking on host inflammatory responses.
E-mail: xxue@nshs.edu
Name: Hima Tam Tam, MD
Position: MFM Fellow
Education: M.B.B.S. 2000 The University of the West Indies
Research: Anti-inflammatory effects of magnesium in pre-term labor
E-mail: hbtamtam@nshs.edu
Name: Monica Sood, MD
Position: MFM Fellow
Education: M.D. 2003 University of CA, Irvine College of Medicine
Research: Anti-inflammatory effects of magnesium in pre-term labor
E-mail: msood@nshs.edu
Collaborators:
Barbara Sherry, PhD
Christine Metz, PhD
Lab Head
Associate Investigator
cmetz@nshs.edu
The Feinstein Institute for Medical Research
350 Community Drive, 4th Floor
Tel: 516-562-3403
Fax: 516-562-1022
Education:
B.S. 1986 Cornell University
M.S. 1988 Cornell University
Ph.D. 1993 New York University, Sackler Institute of Graduate Biomedical Studies
Appointments:
Research Director of Research, Department of Ob-GYN, Maternal Fetal Medicine Fellowship Program
Associate Professor, Elmezzi Graduate School of Molecular Medicine
Research Summary:
Endothelial cells line the body’s blood vessels to create ‘slippery tubes’ which facilitate the rapid transport of blood throughout the body. Almost every inflammatory condition is associated with tissue damage caused by excessive and/or sustained endothelial cell activation and immune cell infiltration. Because most inflammatory diseases involve endothelial cells, the endothelium is a critical target for anti-inflammation strategies. Dr. Metz’s work focuses on the regulation of inflammation, with an emphasis on endothelial cell activation and immune cell trafficking. More specifically, the laboratory is investigating how the cholinergic anti-inflammatory pathway controls endothelial cell activation and immune cell recruitment to prevent organ injury (e.g. kidney, lung, brain) during inflammation, sepsis, and ischemia-reperfusion injury. Using several experimental models of inflammation, along with both cellular and molecular approaches, the lab is beginning to unravel how cholinergic agonists and anti-inflammatory mediators regulate endothelial cell and immune cell responses.
In addition, Dr. Metz oversees the discovery and development of novel diagnostics and therapeutics for human disease by collaborating with clinicians throughout the North Shore-LIJ Health System. Dr. Metz is the Co-Director of the Tissue Donation Program, which provides valuable human specimens for translational disease-oriented research. As Director of Research for the Maternal Fetal Medicine (MFM) Fellowship Program, Dr. Metz collaborates with Drs. Burton Rochelson, MD and Dawnette Lewis, MD in the Department of Obstetrics-Gynecology (Division of MFM) and the MFM Fellows on research studies using cell-based and experimental models of pre-term labor and pre-eclampsia, inflammatory conditions of pregnancy. Other collaborations within the Health System include: Drs. Barbara Sherry, PhD, Peter Gregersen, MD, and John Lovecchio, MD (Department of Obstetrics and Gynecology) to study early disease markers and genetic risk factors for ovarian cancer; and The Center for Tobacco Control to investigate the effects of smoking cessation on inflammatory responses and to develop improved smoking cessation programs.
Cholinergic regulation of endothelial cell activation in inflammation and sepsis
Sepsis, a leading complication of surgery and trauma, is a condition characterized by a systemic inflammatory response (with excessive cytokine production) associated with infection. Despite numerous advances for the treatment of sepsis, the mortality rate for septic patients is between 20-60%, depending on the severity of their condition. Using experimental models of inflammation and sepsis, we are examining the effects of cholinergic stimulation (through electrical stimulation of the vagus nerve or cholinergic agonists or drugs) on endothelial cell activation and leukocyte trafficking. The endothelium is an important target of anti-inflammation and anti-sepsis strategies (Tracey and Metz, The Comprehensive Treatise on the Endothelium, 2007). The cholinergic anti-inflammatory pathway, originally described by Dr. Kevin Tracey at the Feinstein Institute, is a physiological mechanism that inhibits cytokine production during inflammatory conditions, including sepsis. Electrical stimulation of the efferent vagus nerve, the longest nerve in the body which innervates the heart, stomach, liver, and kidneys, releases the neurotransmitter acetylcholine. Acetylcholine binds to nicotinic acetylcholine receptors present on macrophages and other cells to suppress cytokine production during inflammation (Metz and Tracey, Nature 2005). Likewise, several cholinergic agonists (e.g. nicotine and GTS-21) can bind to nicotinic acetylcholine receptors to dampen inflammation. Initial studies by our laboratory revealed that both vagus nerve stimulation and cholinergic agonists (which bind to nicotinic receptors) suppress endothelial cell activation in vitro and in vivo and block leukocyte trafficking during acute inflammation Saeed et al, JEM 2005). In addition to employing experimental models to study the cholinergic regulation of endothelial cell activation, chemokine production, and leukocyte accumulation in various organs (including the brain, kidney, and lungs), we use human endothelial cell cultures to explore how cholinergic agonists control endothelial cell activation and chemokine production. Current studies focus on the NFκB and STAT3 inflammatory pathways. Interestingly, nicotine exhibits anti-depressant activity. Therefore, we are also interested in investigating how cholinergic agonists and anti-depressants regulate endothelial cell activation and inflammatory responses during depression. Our ongoing studies are expected to improve the understanding of how cholinergic signaling controls endothelial cell activation and leukocyte trafficking in vivo. This work has been funded, in part, by NIH-NIGMS.
Regulation of Kidney Ischemia-Reperfusion Injury by Cholinergic Agonists
Kidney ischemia reperfusion injury is a leading cause of acute renal failure. The incidence of acute renal failure is increasing. Acute renal failure is common in patients after trauma, hemorrhagic shock, cardiopulmonary bypass surgery, and sepsis. The mortality rate for patients with both acute renal failure and sepsis can be as high as 70%. Currently, there are no therapeutic agents for preventing or treating acute renal failure. Using experimental models of renal ischemia-reperfusion injury, we explored the potential role of cholinergic agonists (e.g. nicotine and GTS-21) in protecting against renal ischemia-reperfusion injury. The advantage of this therapeutic strategy is that it targets numerous inflammatory pathways simultaneously. In collaboration with NSUH Pathologists, Drs. Myron Sussin, MD (retired) and Douglas Charney, MD, we have shown that administration of cholinergic agonists suppress ischemia-induced kidney tissue damage (Yeboah et al, Kidney Int’l 2008). Our laboratory has characterized the expression of nicotinic acetylcholine receptors, targets of anti-inflammatory cholinergic agonists, within the kidney under normal conditions and following ischemia-reperfusion injury (Yeboah et al, Am J Physiol Renal Physiol 2008). Our data suggest that cholinergic agonists exert anti-inflammatory effects within the kidney. Current studies are investigating the effects of cholinergic agonist administration on chronic renal damage following ischemia-reperfusion injury, including proteinuria, renal T lymphocyte and macrophage infiltration, and renal fibrosis. Further ongoing studies are examining the cellular and molecular mechanisms whereby cholinergic agonists protect the kidney from ischemic and inflammatory injury.
The Effects Of Smoking Cessation On Inflammatory Responses
Our laboratory collaborates with the Center for Tobacco Control (part of the North Shore-LIJ Health System) on several projects related to smoking cessation (or quitting smoking). Our primary interest it to examine the effects of nicotinic acetylcholine receptor agonists, including nicotine and varenicline, used for smoking cessation on inflammatory responses. In a pilot study funded by the American Heart Association, we examined the effects of quitting smoking on a panel of circulating inflammatory biomarkers associated with cardiovascular disease in ‘at risk’ women during the smoking cessation process (Reichert et al, Chest 2009). We found significant reductions in several serum inflammatory biomarkers linked to cardiovascular disease over the course of smoking cessation. These observations support the anti-inflammatory role of nicotine. In addition, they suggest that there are rapid and measurable consequences of quitting smoking on inflammatory biomarkers in women at risk for cardiovascular disease. Additional, larger studies including diverse smokers seeking to quit smoking will be required to confirm our results. If confirmed, these changes in ‘measurable milestones’ could serve as motivating factors to assist smokers to quit. In addition, we are collaborating with Dr. Peter Gregersen, MD, to identify potential genes involved in the addiction to cigarettes and the ability (or inability) to quit smoking.
Identification of biomarkers associated with alcohol abuse
Our laboratory is working with Feinstein chemist Yousef Al-Abed, PhD, to develop reliable methods to detect acute and chronic alcohol abuse. Acetaldehye is produced by the body following alcohol intake and we have attempted to generate antibodies specific for biomarkers formed in the presence of acetaldehyde. Ultimately, these antibodies could be used to detect biomarkers of alcohol abuse in the blood following binge drinking or chronic alcohol abuse. This work was funded by NIAAA.
Maternal Fetal Medicine Research Program
Our laboratory collaborates with clinicians and fellows in the Division of Maternal Fetal Medicine (MFM) in the Department of Obstetrics and Gynecology. One project is exploring the anti-inflammatory role of magnesium sulfate, a tocolytic agent used to delay pre-term labor. The precise mechanisms of action of magnesium sulfate in pre-term labor are not completely understood. In collaboration with Dr. Burton Rochelson, MD, we discovered that magnesium sulfate suppressed the activation of human umbilical vein endothelial cells through NFB (Rochelson et al, J Repro Immunol 2007). These unexpected observations have important implications in light of recent studies showing that maternal administration of magnesium sulfate is associated with a reduction in cerebral palsy in preterm babies. Current studies in the laboratory are exploring the potential regulation of maternal and fetal inflammation by magnesium sulfate using in vitro and in vivo models.
Additional studies focus on the modulation of maternal and fetal inflammatory responses associated with pre-eclampsia by the cholinergic anti-inflammatory pathway. Numerous studies show that smoking is protective against pre-eclampsia, a condition characterized by hypertension and proteinuria in the second trimester of pregnancy. Pre-eclampsia, often referred to as the septicemia of pregnancy, is characterized by maternal/placental inflammation and can progress to eclampsia, a potentially deadly condition of pregnancy. While smoking is harmful to both the mother and fetus and should be avoided, based on the anti-inflammatory activities of nicotine (a cholinergic agonist and major component of cigarettes) we hypothesized that nicotine was protective against pre-eclampsia. Our early findings revealed that nicotine and other cholinergic agonists suppress cytokine production by cells isolated from the human placenta through the NFκB pathway (Dowling et al Mol Med 2007). Further studies focus on exploring the regulation of maternal and fetal inflammation by cholinergic stimulation using experimental models of pre-eclampsia and pre-term labor.
Our laboratory continues to collaborate with Dr. Akoum from Laval University to explore the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of endometriosis. In addition, we collaborate with many investigators at The Feinstein on other MIF-related projects (Drs. E. Miller, K. Ojamma, and Y. Al-Abed).
Ovarian Cancer Discovery Program
We are currently developing a collaborative discovery program to identify potential risk factors and early diagnostic markers for ovarian cancer. In conjunction with the Tissue Donation Program, we are collaborating with Drs. Barbara Sherry, PhD, Peter Gregersen, MD, John Lovecchio, MD, and the members of the Department of Gynecology Oncology to collect important biological samples for this program.
Lab Members;
Name: Oonagh Dowling, PhD
Position: Research Scientist
Education: Ph.D. 1998 Dublin City University
Research: Obstetrics and Gynecology-related research; cholinergic anti-inflammatory projects.
E-mail: odowling@nshs.edu
Name: Prodyot Chatterjee, PhD
Position: Research Scientist
Education: Ph.D. 1996 Jadavpur University
Research: Cholinergic regulation of endothelial cell activation and leukocyte recruitment: signaling mechanisms and drug screening studies.
E-mail: pchatter@nshs.edu
Name: Xiangying Xue, MD
Position: Research Associate
Education: M.D. 1983 China Medical University
Research: Biomarkers of alcohol abuse; cholinergic regulation of leukocyte trafficking; the effects of depression and smoking on host inflammatory responses.
E-mail: xxue@nshs.edu
Name: Hima Tam Tam, MD
Position: MFM Fellow
Education: M.B.B.S. 2000 The University of the West Indies
Research: Anti-inflammatory effects of magnesium in pre-term labor
E-mail: hbtamtam@nshs.edu
Name: Monica Sood, MD
Position: MFM Fellow
Education: M.D. 2003 University of CA, Irvine College of Medicine
Research: Anti-inflammatory effects of magnesium in pre-term labor
E-mail: msood@nshs.edu
Collaborators:
Barbara Sherry, PhD
Kevin J Tracey, MD
Peter K Gregersen, MD
Yousef Al-Abed, MD
Edmund Miller, PhD
Kaie Ojamma, PhD
Burton Rochelson, MD
Dawnette Lewis, MD
John Lovecchio, MD
Douglas Charney, MD
Arunabh Talwar, MD
Select Publications:
Reichert V, Xiangying X, Bartscherer D, Jacobsen D, Fardellone C, Folan P, Kohn N, Talwar A, Metz, CN (2009) A Pilot Study to Examine the Effects of Smoking Cessation on Serum Markers of Inflammation in Women at Risk for Cardiovascular Disease Chest (Feb 18, 2009 Epub ahead of print).
Yeboah MM, Xue X, Javdan M, Susin M, Metz CN. (2008) Nicotinic acetylcholine receptor expression and regulation in the rat kidney after ischemia-reperfusion injury. Am J Physiol Renal Physiol. 295(3):F654-61.
Yeboah M, Xue X, Duan B, Ochani M, Tracey KJ, Susin M, and Metz CN (2008) Cholinergic agonists attenuate renal ischemia-reperfusion injury in rats. Kidney International 74(1):62-9.
Tracey, KJ and Metz, CN (2007) Chapter: Brain endothelial cells bridge neural and immune networks. In: vascular bed/organ in health and disease. In: The Comprehensive Treatise on the Endothelium. Editor: W. Aird.
Huston JM, Gallowitsch-Puerta M, Ochani M, Ochani K, Yuan R, Rosas-Ballina M, Ashok M, Goldstein RS, Chavan S, Pavlov VA, Metz CN, Yang H, Czura CJ, Wang H, Tracey KJ. (2007) Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit Care Med. 35(12):2762-2768.
Dowling O, Rochelson B, Way K, Al-Abed Y, Metz CN. (2007) Nicotine inhibits cytokine production by placenta cells via NFkappaB: Potential role in pregnancy-induced hypertension (PIH). Molecular Med 13(11-12) 576-83.
Rochelson B, Dowling O, Schwartz N, Metz CN (2007). Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFκB pathway. J Repro Immunol. 23(2):101-107.
McDevitt MA, Xie J, Shanmugasundaram G, Griffith J, Liu A, McDonald C, Thuma P, Gordeuk VR, Metz CN, Mitchell R, Keefer J, David J, Leng L, Bucala R (2006) A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia. J Exp Med 203(5):1185-96.
Lin X, Sakuragi T, Metz CN, Ojamma K, Skopicki HA, Wang P, Al-Abed Y, Miller EJ (2005) Macrophage migration inhibitory factor within the alveolar spaces induces changes in the heart during late experimental sepsis. Shock 24(6):556-63.
Saeed RW, Varma S, Peng-Nemeroff T, Sherry B, Balakhaneh D, Huston J, Tracey KJ, Al-Abed Y, Metz CN. (2005) Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med. 201(7):1113-23.
Chagnon F, Metz C, Bucala R, Lesur O (2005) Endotoxin-induced myocardial dysfunction: Effects of macrophage migration inhibitory factor (MIF) neutralization. Circulation Res. 96(10):1095-102.
Morin M, Bellehumeur C, Therriault MJ, Metz C, Maheux R, Akoum A (2005) Elevated levels of macrophage migration inhibitory factor in the peripheral blood of women with endometriosis. Fertil. Steril. 83(4):865-872.
Kar S, Metz C and McMahon-Pratt D. (2005) CD4+ T cells play a dominant role in protection against New World leishmaniasis induced by the amastigote single strand-specific nuclease, P-4. Infection and Immunity. 73(6):3823-3827.
Cao WG, Morin M, Metz C, Maheux R and Akoum A. (2005) Stimulation of macrophage migration inhibitory factor expression in endometrial stromal cells by interleukin 1, beta involving the nuclear transcription factor NFkb. Biol Reprod. 73(3):565-570.
Metz CN, Tracey KJ. It takes nerve to dampen inflammation. (2005) Nat Immunol. (8):756-7.
Saeed RW, Varma S, Peng T, Tracey KJ, Sherry B, Metz CN. (2004) Ethanol blocks leukocyte recruitment and endothelial cell activation in vivo and in vitro. J Immunol. 173(10):6376-83.
Metz CN, Gregersen PK, and Malhotra A. (2004). Metabolism and biochemical effects of nicotine for primary care providers. Medical Clinics of North America 88(6):1399-413.
Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Wang H, Metz C, Miller EJ, Tracey KJ, Ulloa L. (2004) Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 10(11):1216-1221.
Saeed RW, Varma S, Peng T, Tracey KJ, Sherry B, Metz CN. (2004) Ethanol blocks leukocyte recruitment and endothelial cell activation in vivo and in vitro J Immunol. 173(10):6376-6383.
Pan JH, Sukhova GK, Yang JT, Wang B, Xie T, Fu H, Zhang Y, Satoskar AR, David JR, Metz CN, Bucala R, Fang K, Simon DI, Chapman HA, Libby P, Shi GP (2004) Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation. 109(25):3149-3153.
Saeed RW, Peng T, Metz CN (2003) Ascorbic acid blocks the growth inhibitory effect of tumor necrosis factor-alpha on endothelial cells. Exp. Bio. Med. 228(7): 855-865.
Leng L, Metz C, Fang Y, Xu J, Donnelly S, Baugh J, Delohery T, Chen Y, Mitchell RA, Bucala R (2003) MIF signal transduction initiated by binding to CD74. J Exp. Med. 197(11) 11467-11476.
Denkinger C, Denkinger M, Kort J, Metz C, Forsthuber T. (2003) Effects of blockade of macrophage migration inhibitory factor (MIF) on EAE: Amelioration of acute disease by inhibition of homing of encephalitogenic T cells to the central nervous system J. Immunol.170(3): 1274-82.
Petrenko O, Fingerle-Rowson G, Mitchell R, Metz CN. (2003) MIF deficiency is associated with altered cell growth and reduced susceptibility to Ras-mediated transformation. J Biol Chem. 278(13): 11078-11082.
Akoum A, Kong J, Metz C, Beaumont M-C. (2002) Spontaneous and stimulated secretion of monocyte chemotactic protein-1 and macrophage migration inhibitory factor by peritoneal macrophages of women with and without endometriosis. Fertility and Sterility 77:989-994.
deJong YP, Abadia-Molina AC, Satoskar AR, Clarke K, Rietdijk ST, Faubion WA, Mizoguchi E, Metz CN, Sahli MA, ten Hove T, Keates AC, Lubetsky JB, Farrell RJ, Michetti P, van Deventer SJ, Lolis E, David JR, Bhan AK, Terhorst C. (2001) Development of chronic colitis is dependent on the cytokine MIF. Nat Immunol. 2:1061-6.
Hartlapp I, Abe R, Saeed R, Peng T, Voelter W, Bucala R, Metz CN. (2001) Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis in vivo. FASEB J. 15:2215-2224.
Brown FG, Nikolic-Paterson DJ, Chadban SJ, Dowling J, Jose M, Metz CN, Bucala R, Atkins RC. (2001) Urine macrophage migration inhibitory factor concentrations as a diagnostic tool in human renal allograft rejection. Transplantation. 71(12):1777-1783.
Abe R, Donnelly DC, Peng T, Bucala R, Metz CN. (2001) Peripheral blood fibrocytes: Differentiation pathway and migration to wound sites. J. Immunol. 166 (12): 7556-7562.
Batliwalla FM, Damle RN, Metz C, Chiorazzi N, and Gregersen PK (2001) Simultaneous flow cytometric analysis of cell surface markers and telomere length: Analysis of human tonsillar B cells. J. Immunol. Methods. 247 (1-2): 103-109.
Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hultner L, Heumann D, Mannel D, Bucala R, and Glauser MP (2000) Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat. Med. 6 (2):164-170.
Metz CN, and Bucala R (2000) Review: MIF (Chapter 7) Oppenheim JJ and Feldmann M. (Eds.) Cytokine Reference Vol. I. Ligands. Academic Press. Electronic Citation, www.apnet.com/cytokine.
Lan HY, Yang N, Nikolic-Paterson DJ, Yu XQ, Mu W, Isbel NM, Metz CN, Bucala R, and Atkins RC (2000) Expression of macrophage migration inhibitory factor in human glomerulonephritis. Kidney Int. 57 (2):499-509.
Chesney J, Metz, CN, Bacher M, Peng T, Meinhardt A, and Bucala R. (1999) An essential role of macrophage migration inhibitory factor (MIF) in angiogenesis and the growth of a murine lymphoma. Molecular Medicine 5:181-191.
Rossi AG, Haslett C, Hirani N, Greening AP, Rahman I, Metz CN, Bucala R, and Donnelly SC (1998) Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma. J. Clin. Invest. 101 (12):2869-2874
Lan HY, Yang N, Brown FG, Isabel NM, Nikolic-Paterson DJ, Mu W, Metz CN, Bacher M, Atkins RC, and Bucala R (1998) Macrophage migration inhibitory factor expression in human renal allograft rejection. Transplantation. 66 (11):1465-1471.
Tesch GH, Nikolic-Paterson DJ, Metz CN, Mu W, Bacher M, Bucala R, Atkins RC, and Lan HY (1998) Rat mesangial cells express macrophage migration inhibitory factor in vitro and in vivo. J. Am. Soc. Nephrol. 9 (3):417-424.
Bacher M, Meinhardt A, Lan HY, Mu W, Metz CN, Chesney JA, Calandra T, Gemsa D, Donnelly T, Atkins RC, and Bucala R (1997) Migration inhibitory factor expression in experimentally induced endotoxemia. Am.J.Pathol. 150 (1):235-246.
Mikulowska A, Metz CN, Bucala R, and Holmdahl R (1997) Macrophage migration inhibitory factor is involved in the pathogenesis of collagen type II-induced arthritis in mice. J. Immunol. 158 (11):5514-5517.
Metz CN and Bucala R (1997) Role of macrophage migration inhibitory factor in the regulation of the immune response. Adv. Immunol. 66:197-223:197-223.
Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, and Bucala B (1995) MIF as a glucocorticoid-induced modulator of cytokine production. Nature. 377:68-71.
Metz CN, Brunner G, Choi-Muira NH, Nguyen H, Gabrilove J, Caras IW, Altszuler N, Rifkin DB, Wilson EL, and Davitz MA (1994) Release of GPI-anchored membrane proteins by a cell-associated GPI-specific phospholipase D. EMBO J. 13 (7):1741-1751.
Abe M, Harpel JG, Metz CN, Nunes I, Loskutoff DJ, and Rifkin DB (1994) An assay for transforming growth factor-b using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct. Anal.Biochem. 216 (2):276-284.
Metz CN, Zhang YY, Guo Y, Tsang TC, Kochan JP, Altszuler N, and Davitz MA (1991) Production of the glycosylphosphatidylinositol-specific phospholipase D by the islets of Langerhans. J.Biol.Chem. 266 (27):17733-17736.
Metz CN, Schenkman S, and Davitz MA (1991) Characterization of the plasma glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD). Cell Biol.Int.Rep. 15 (9):875-882.
Metz CN, Thomas P, and Davitz MA (1992) Immunolocalization of a glycosylphosphatidyl-inositol-specific phospholipase D in mast cells found in normal tissue and neurofibromatosis lesions. Am.J.Pathol. 140 (6):1275-1281.