Cardiopulmonary Research

Edmund J. Miller, PhD CChem FRSC


Brief Description of Research


Our research focuses on lung inflammation and the role of the lung as an inflammatory organ. Our studies involve both acute and chronic disorders that impact the lung.

Our group has discovered that, during severe illness, the lungs synthesize and release an important immune system messenger, called macrophage migration inhibitory factor (MIF), which affects cardiac and circulatory function and other vital organs, causing dysfunction and leading to multi-organ failure. We are closely studying the role of MIF at the molecular level with the goal of identifying new ways to control the inflammatory response to prevent or treat lung damage and death associated with disease.

In particular, we are studying the role of this important molecule in 1) severe sepsis,  a major inflammatory response to infection that kills almost a quarter of a million hospitalized patients in the United States each year; 2) acute myocardial infarction (heart attack), a leading cause of death in the United States; and 3) pulmonary hypertension, a condition characterized by vascular growth and proliferation, leading to increased pulmonary vascular resistance, pulmonary arterial pressure, right ventricular failure and death. Our studies examine the inflammatory responses involved in the development and progression of the disease.

Contact Information

Edmund J. Miller, PhD CChem FRSC
Chief, Surgical Immunology
Director Cardiopulmonary Research
Department of Surgery

North Shore-Long Island Jewish Medical Center
Associate Investigator
The Feinstein Institute for Medical Research
350 Community Drive
Manhasset, NY 11030

Phone: (516) 562-3401    Fax: (516) 562-1022

emiller@nshs.edu

Associate Professor of Surgery and Medicine   
Albert Einstein College of Medicine
Bronx, NY 10461

Current Projects


Project 1 The lung as a source of inflammation in sepsis
Project 2  Aging and its effects on acute inflammation
Project 3  Inflammatory responses associated with myocardial infarction
Project 4  The inflammatory response in chronic lung diseases

Laboratory Members


Xinchun Lin, MD
Research Scientist

Kiyokazu Koga, MD
PhD Student in Molecular Medicine

Kiochiro Takahashi, MD, PhD
Postdoctoral Fellow

Yinzhong Zhang, MD PhD
Postdoctoral Fellow

Helena Linge, PhD
Postdoctoral Fellow

Lin Mantell, MD PhD
Adjunct Investigator

Clinical Fellows


Hans Lee, MD
Pulmonary Critical Care  Medicine

Omonuwa Kennedy, MD
Pulmonary Critical Care  Medicine

Rafat Ahmed, MD
Pediatrics (Steven and Alexandra Cohen Children's Medical Center of New York)         


Current and Selected Previous Grant Support to Cardiopulmonary Research 


Principal Investigator
 “The Lung as a Source of Inflammation in Sepsis”
Agency: NIH/ NHLBI 

“MIF in Inflammation-Associated Lung Tumorigenesis”
Agency:  The Feinstein Institute for Medical Research 

 “Mechanisms Regulating Human Neutrophil Apoptosis”
Agency: NIH/NIGMS

“The Role of Staphylococcal Toxins and IL-8 in ARDS”
 Agency: NIH/ NHLBI
 
“The Control of Malignant Melanoma by  ?-Chemokine Inhibition”
Agency: Elsa U Pardee Foundation
 
Co-Investigator 
“Endogenous inhibitors of MIF inflammatory activity during sepsis”
Agency:  American Heart Association    (PI Y Al-Abed)

International Fellowship  (H Linge)
Agency:  Gemzéus Foundation  

“Peptide Mediators of Lung Injury in the Adult Respiratory Distress Syndrome”
Agency: NIH/ NHLBI   (PIA Cohen)


Recent Peer-Reviewed Publications (Selected from more than 210 publications)


1. Miller EJ, Cohen AB, Nagao S, Griffith D, Maunder RJ, Martin TR, Weiner-Kronish JP, Sticherling, Christophers ME, and Matthay, MA: Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis 146:427, 1992.

2. Miller,E.J., Cohen,A.B., Carr,F.K., Hayashi,S., Chiu,C.Y., Lee Ng,C.T., Mullenbach, G. High Yields  of Interleukin 8 produced by a synthetic gene expressed in Escherichia coli and purified with a single antibody affinity column. Protein Expression and Purification 6: 357-362, 1995.

3. Hayashi S, Kurdowska A, Cohen AB, Stevens MD, Fujisawa N, and Miller EJ: A synthetic peptide inhibitor for alpha-chemokines inhibits the growth of melanoma cell lines. J Clin Invest 99:2581, 1997.

4. Fujisawa N, Hayashi S, Kurdowska A, Noble JM, Naitoh K, and Miller EJ: Staphylococcal enterotoxin A-induced injury of human lung endothelial cells and IL-8 accumulation are mediated by TNF-alpha. J Immunol 161:5627, 1998.

5. Fujisawa N, Hayashi S, Kurdowska A, Carr FK, and Miller EJ: Inhibition of GROalpha-induced human endothelial cell proliferation by the alpha-chemokine inhibitor antileukinate. Cytokine 11:231, 1999.

6. Fujisawa N, Sakao Y, Hayashi S, Hadden WA 3rd, Harmon CL, and Miller EJ: a-Chemokine growth factors for adenocarcinomas; a synthetic peptide inhibitor for alpha-chemokines inhibits the growth of adenocarcinoma cell lines. J Cancer Res Clin Oncol 126:19, 2000.

7. Sakao Y, Kajikawa O, Martin TR, Nakahara Y, Hadden WA 3rd, Harmon CL, and Miller EJ: Association of IL-8 and MCP-1 with the development of reexpansion pulmonary edema in rabbits. Ann Thorac Surg 71:1825, 2001.

8. Hayashi,S., Yatsunami, J., Fukuno,Y., Miller E.J. Hexapeptide inhibitor for CXC-chemokine receptor,  Antileukinate, suppressed bleomycin-induced acute lung injury in mice. Lung 180:339-48, 2003.

9. Hu M, Miller EJ, Lin X, and Simms HH: Transmigration across a lung epithelial monolayer delays apoptosis of polymorphonuclear leukocytes. Surgery 135:87, 2004.

10. Wang, H.L., H., Ochani, M., Li, H., Lin,X., Justiniani, M., Al-Abed, Y., Wang, H., Metz, C.,  Miller, E.J., Tracey, K.J., Ulloa, L. Cholinergic agonists inhibit HMGB1 release and improve survival in established severe sepsis. Nature Medicine  10:1216-1221, 2004.

11. Lin X, Yang H., Sakuragi, T., Hu, M., Mantell L., Hayashi, S., Al-Abed, Y.,  Tracey, K.J., Ulloa, L.,    Miller E.J., a-Chemokine Receptor Blockade Reduces High Mobility Group Box 1 (HMGB1)    Protein Induced Lung Inflammation and Injury and Improves Survival in Sepsis  AJP- Lung Cellular and Molecular Physiology  289: L583-L590, 2005.

12. Lin, X. Sakuragi, T., Metz, C., Ojaama K., Skolpicki H.A. Wang, P. Al-Abed, Y.,  Miller E.J.  Macrophage Migration Inhibitory Factor  Within the Alveolar Spaces Induces Changes in the Heart  During Late Experimental Sepsis Shock 24(6):556-563, 2005.

13. Al-Abed, Y., Dabideen, D.  Aljabari,B., Valster A, Lin, X.,  Ochani, M., Tanovic,M.,  Bacher,  M., Nicoletti, F., Metz, C., Pavlov,V. Miller E.J.,  Tracey, K.J. ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis.  Journal of Biological Chemistry 280: 36541-36544, 2005.

14. Hirayama S., Shiraishi T., Shirakusa T., Higuchi T., Miller E.J. Prevention of Neutrophil Migration Ameliorates Rat Lung Allograft Rejection Molecular Medicine 12: 208-213, 2006.

15. Dabideen, D., Cheng, K., Aljabari, B., Miller, E.J., Pavlov, V.A. and Al-Abed Y. Phenolic hydrazones are potent inhibitors of MIF proinflammatory activity and survival improving agents in sepsis.      Journal of Medicinal Chemistry 19;50(8):1993-1997, 2007.

16. Sakuragi, T., Lin, X., Metz, C., Ojamaa,K., Kohn,N. Al-Abed, Y., Miller, E.J. Lung-Derived Macrophage Migration Inhibitory Factor in Sepsis Induces Cardio-Circulatory Depression.  Surgical Infections  8 (1), 33-44, 2007.

17. Merchant, S., Nadaraj, S., Chowdhury,D., Parnell, V.A., Sison, C.,  Miller E.J., Ojamaa, K.  Macrophage Migration inhibitory factor in pediatric patients undergoing surgery for congenital heart repair.  Molecular Medicine 14(3-4):124-30 2008. 

U.S. Patents


1. Cohen AB, Miller EJ, Nagao S, Carr FK: Peptide inhibitors of neutrophil activating factor induced chemotaxis. US Patent #5,079,228 (issued January 7, 1992)

2. Cohen AB, Miller EJ, Kurdowska AK, Hayashi S, Tuttle R: Methods of inhibiting CXC intercrine molecules. US Patent #5,965,536 (issued October 12, 1999)

3. Miller EJ, Hayashi S: Peptide tumor cell growth inhibitors. US Patent #6,110,889 (issued August 29, 2000)

4. Miller EJ, Hayashi S: Peptide tumor cell growth inhibitors. US Patent #6,355,619 (issued March 12, 2002)


Last Update

April 9, 2010
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