Associate Professor of  Medicine and Associate Professor of  Surgery Albert Einstein College of Medicine;   Scientific Advisor, Jinan Academy of Sciences, PR China

Education: BSc Applied Biology; MSc Chemical Analysis; PhD Biochemistry 

Phone:  (516) 562-3401 

Fax: (516) 562-1131

Dr. Miller’s research focuses on lung inflammation and the role of the lung as an inflammatory organ. The studies in his laboratory involve both acute and chronic disorders that impact the lung.
 
His group has discovered that the lungs synthesize and release an important immune system messenger, called macrophage migration inhibitory factor (MIF), during severe illness. This affects cardiac and circulatory function and other vital organs, causing dysfunction and leading to multi-organ failure. They 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 inflammation and injury and death associated with disease.
 
In particular, they are studying the role of this important molecule in 1) severe sepsis, a major inflammatory response to infection; 2) pulmonary hypertension, a condition characterized by vascular growth and proliferation, leading to increased pulmonary vascular resistance, pulmonary arterial pressure, right ventricular failure and death. Their studies examine the inflammatory responses involved in the development and progression of the disease. and 3) acute myocardial infarction (heart attack), a leading cause of death in the United States;
 
Sepsis
Severe sepsis is a major inflammatory response to infection that kills almost a quarter of a million hospitalized patients in the United States each year. Recently, Dr. Miller and his colleagues have found that lung injury caused by severe sepsis induces detrimental changes in other organs, particularly the heart. The group has discovered that during infection the lungs synthesize and release MIF, which affects cardiac and circulatory function and other vital organs, causing dysfunction and leading to multi-organ failure.
 
Pulmonary Hypertension
Pulmonary Hypertension (PH) is a condition characterized by vascular growth and proliferation, leading to increased pulmonary vascular resistance, pulmonary arterial pressure, right ventricular failure and death. PH can be idiopathic or associated with other conditions, including connective tissue diseases, HIV infection, and portal hypertension. PH demonstrates rapid deterioration after diagnosis, with an average survival time for primary pulmonary hypertension only 2.8 years, and an estimated 5 year survival rate of between 21-34%. Their studies are examining the inflammatory responses involved in the development and progression of the disease.

Acute myocardial infarction
Heart disease is the leading cause of death in the United States and 71% of heart disease is related to coronary artery disease. Heart attacks (acute myocardial infarction) occur in 1.2 million people in the United States each year. Although the mortality from myocardial infarction has been steadily decreasing, the number of surviving patients developing congestive heart failure, fatal arrhythmias and ventricular aneurism formation related to ischemic coronary disease is increasing. Ischemic stress induces an inflammatory response, but excessive inflammation may lead to cell apoptosis and necrosis and prevents myocardial remodeling. Their studies in this area focus on therapeutic strategies to minimize myocardial necrosis and apoptosis and optimize cardiac repair following myocardial infarction. Therefore, careful control of the inflammatory response could potentially improve the cardiac function after myocardial infarction. 

Lab Members:

Name:  Ke Lin, MS
Position:  Research Associate
Research:   Studies the MIF molecule and its role in sepsis.
E-mail:   klin@nshs.edu

Name:   Yinzhong Zhang, MD, PhD
Position:   Postdoctoral Research Fellow
Research:   Studies Pulmonary Hypertension.
E-mail:   yzhang2@nshs.edu

Name:   Helena Linge, PhD
Position:   Institute Scientist
Research:   Studies inflammation and aging.
E-mail:   hlinge@nshs.edu

Name:   Kiyokazu Koga, MD
Position:  Graduate Student, Elmezzi College
Research:   Studies acute myocardial infarction.
E-mail:   kkoga@nshs.edu 

Select Publications:

Bruchfeld, A., J. J. Carrero, A. R. Qureshi, B. Lindholm, P. Barany, O. Heimburger, M. Hu, X. Lin, P. Stenvinkel, and E. J. Miller. 2009. Elevated Serum Macrophage Migration Inhibitory Factor (MIF)

Concentrations in Chronic Kidney Disease (CKD) Are Associated with Markers of Oxidative Stress and Endothelial Activation. Mol Med 15:70.

Merchant, S., S. Nadaraj, D. Chowdhury, V. A. Parnell, C. Sison, E. J. Miller, and K. Ojamaa. 2008. Macrophage migration inhibitory factor in pediatric patients undergoing surgery for congenital heart repair. Mol Med 14:124.

Dhanantwari, P., S. Nadaraj, A. Kenessey, D. Chowdhury, Y. Al-Abed, E. J. Miller, and K. Ojamaa. 2008. Macrophage migration inhibitory factor induces cardiomyocyte apoptosis. Biochem Biophys Res Commun 371:298.

Zaher, T. E., E. J. Miller, D. M. Morrow, M. Javdan, and L. L. Mantell. 2007. Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells. Free Radic Biol Med 42:897.

Sakuragi, T., X. Lin, C. N. Metz, K. Ojamaa, N. Kohn, Y. Al-Abed, and E. J. Miller. 2007. Lung-derived macrophage migration inhibitory factor in sepsis induces cardio-circulatory depression. Surg Infect (Larchmt) 8:29.

Pavlov, V. A., M. Ochani, L. H. Yang, M. Gallowitsch-Puerta, K. Ochani, X. Lin, J. Levi, W. R. Parrish, M. Rosas-Ballina, C. J. Czura, G. J. Larosa, E. J. Miller, K. J. Tracey, and Y. Al-Abed. 2007. Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit Care Med 35:1139.

Morrow, D. M., T. Entezari-Zaher, J. Romashko, 3rd, A. O. Azghani, M. Javdan, L. Ulloa, E. J. Miller, and L. L. Mantell. 2007. Antioxidants preserve macrophage phagocytosis of Pseudomonas aeruginosa during hyperoxia. Free Radic Biol Med 42:1338.

Laragione, T., M. Brenner, N. C. Yarlett, A. Mello, E. J. Miller, C. N. Metz, B. Sherry, and P. S. Gulko. 2007. The arthritis severity quantitative trait locus Cia7 regulates neutrophil migration into inflammatory sites. Genes Immun 8:147.

Laragione, T., N. C. Yarlett, M. Brenner, A. Mello, B. Sherry, E. J. Miller, C. N. Metz, and P. S. Gulko. 2007. The arthritis severity quantitative trait loci Cia4 and Cia6 regulate neutrophil migration into inflammatory sites and levels of TNF-alpha and nitric oxide. J Immunol 178:2344.

Gao, L., C. Flores, S. Fan-Ma, E. J. Miller, J. Moitra, L. Moreno, R. Wadgaonkar, B. Simon, R. Brower, J. Sevransky, R. M. Tuder, J. P. Maloney, M. Moss, C. Shanholtz, C. R. Yates, G. U. Meduri, S. Q. Ye, K. C. Barnes, and J. G. Garcia. 2007. Macrophage migration inhibitory factor in acute lung injury: expression, biomarker, and associations. Transl Res 150:18.

Dabideen, D. R., K. F. Cheng, B. Aljabari, E. J. Miller, V. A. Pavlov, and Y. Al-Abed. 2007. Phenolic hydrazones are potent inhibitors of macrophage migration inhibitory factor proinflammatory activity and survival improving agents in sepsis. J Med Chem 50:1993.

Crichlow, G. V., K. F. Cheng, D. Dabideen, M. Ochani, B. Aljabari, V. A. Pavlov, E. J. Miller, E. Lolis, and Y. Al-Abed. 2007. Alternative chemical modifications reverse the binding orientation of a pharmacophore scaffold in the active site of macrophage migration inhibitory factor. J Biol Chem 282:23089.

Babu, A. N., T. Murakawa, J. M. Thurman, E. J. Miller, P. M. Henson, M. R. Zamora, N. F. Voelkel, and M. R. Nicolls. 2007. Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis. J Clin Invest 117:3774.

Sakuragi, T., X. Lin, C. N. Metz, K. Ojamaa, N. Kohn, Y. Al-Abed, and E. J. Miller. 2006. Lung-Derived Macrophage Migration Inhibitory Factor in Sepsis Induces Cardio-Circulatory Depression. Surgical Infection IN PRESS.

Hirayama, S., T. Shiraishi, T. Shirakusa, T. Higuchi, and E. J. Miller. 2006. Prevention of neutrophil migration ameliorates rat lung allograft rejection. Mol Med 12:208.

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