Miller, PhD, CChem FRSC
Head, Center for Heart and Lung Research,
The Feinstein Institute for Medical Research
Director, Cardiopulmonary Research Laboratory,
The Feinstein Institute for Medical Research
Professor, Medicine & Molecular Medicine,
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
About the researcher:
Sepsis, Pulmonary Hypertension
Dr. Edmund Miller started his career in science in the pathology department at Kings College Hospital in 1972. He earned a BSc (hons) in applied biology, FIMLS in clinical Chemistry, MSc in chemical analysis, a PhD in biochemistry from London University, and was a chartered chemist.
In 1998, Dr. Miller was admitted to the Royal Society of Chemistry as a fellow, the highest class of membership. In 2001, he joined Northwell Health as chief of surgical research, focusing on acute lung injury associated with bacterial infections and pulmonary hypertension.
He is currently head of the Center for Heart and Lung Research at The Feinstein Institute for Medical Research, professor of medicine and molecular medicine at Hofstra Northwell School of Medicine and professor at the Elmezzi Graduate School of Molecular Medicine.
Miller focuses his research on lung inflammation and the role of the lung as an inflammatory organ. The studies in his laboratory involve both chronic and acute disorders that affect 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 alters 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 manage the inflammatory response to prevent or treat lung inflammation and injury and death associated with disease. Together with Dr. Yousef Al-Abed, they have shown that the thyroid hormone Thyroxine (T4) is a natural inhibitor of MIF and the normal balance between MIF and T4 is severely disturbed during severe illness.
In particular, they are studying the role of this important molecule in severe sepsis, a major inflammatory response to infection; and 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.
Severe sepsis is a major inflammatory response to infection that kills around a quarter of a million hospitalized patients in the United States each year. Recently, Dr. Miller has found that lung injury provoked 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. Along with Dr. Yousef Al-Abed’s group, they have made the surprising discovery that the thyroid hormone thyroxine (T4) can bind within the inflammatory active site of MIF.
These results demonstrate a new physiological role for T4 as a natural inhibitor of the MIF proinflammatory activities involved in sepsis. This previously unrecognized, clinically relevant, interaction between MIF and T4 in critically ill patients is now the focus of studies to determine if the interaction can be exploited in future therapeutic approaches for the treatment of sepsis.
Pulmonary arterial hypertension (PAH) is a chronic progressive disorder that starts to remodeling of blood vessels in the lung, low oxygen in the blood, right-sided heart failure and death. The disorder is associated with anxiety, cognitive dysfunction and depression. PAH can be idiopathic or linked 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%. The poor prognosis and lack of effective PAH disease modifying agents underscore the need for a better understanding of disease pathogenesis in order to identify new therapeutic approaches. Their studies suggest a key role for MIF in the development of hypoxia-induced pulmonary vascular remodeling and hypertension. They have shown a relationship between MIF in both patients and models of the disease and that inhibition of MIF inflammatory activity may be a useful treatment strategy to inhibit the development and progression of hypoxia-induced vascular remodeling and cognitive dysfunction.
While their current studies focus on the interactions of MIF and T4 in the pathogenesis of PAH, data achieved in the study will be directly relevant to other cardiopulmonary disease states in which MIF is increased including stroke, cardiovascular disease, myocardial infarction, pulmonary fibrosis and obstructive sleep apnea.
North East Thames Polytechnic, London, UK
Degree: BSc (honors)
Field of study: Applied biology
Thames Polytechnic, London, UK
Field of study: Analytical chemistry
King’s College, London University, UK
Field of study: Biochemistry
Sr Research Assist
Post Doc Res Fellow(RI)(GF)
Ping Wang MS
Senior Research Assistant
Honors and awards
Parker B. Francis Fellow in Pulmonary Research
Member, American Thoracic Society
Chairman, IACUC University of Texas Health Center at Tyler, TX
American Heart Association (Texas Affiliate) Central Research Review Committee
Member, American Association of Immunologists
Japanese Society for the Promotion of Science Fellowship for biomedical research in Japan
Elected Fellow of The Royal Society of Chemistry (CChem FRSC)
Member, NIH Special Emphasis Panel Review Committee
American Heart Association (Western Consortium) Central Research Review Committee
Chairman, IACUC Equine Medical Center & Veterinary Hospital, Gresham TX
Member, Society for Leukocyte Biology
Member, Shock Society
Member, Animal Research Committee (National), Shock Society
Chairman, IACUC Northwell Health Research Institute, Manhasset, NY
Member, Surgical Infection Society
Scientific Advisor, Shandong Academy of Sciences, Jinan, PR China
Member, Society for Critical Care Medicine
Member, Scientific Advisory Board, LeukoDx Ltd, Baltimore, MD
Member, NIH Special Review Committee RFA-HL-11-032 (Lung Tissue for Vascular Research)
Member, NIH Special Review Committee RFA HL-12-021 (Right Ventricular- PAH)
- Lee JY, Linge HM, Ochani K, Lin K, Miller EJ: “Regulation of angiopoietin-2 secretion from human pulmonary microvascular endothelial cells.” Experimental Lung Research 2016, In Press.
- Lee JY, Linge HM, Ochani K, Lin K, Miller EJ: “N-Ethylmaleimide Sensitive Factor (NSF) Inhibition Prevents Vascular Instability following Gram-Positive Pulmonary Challenge.” PLoS One2016, 11(6):e0157837.
- Bruchfeld A, Wendt M, Miller EJ: “Macrophage Migration Inhibitory Factor in Clinical Kidney Disease.” Front Immunol 2016, 7:8.
- Stefaniak J, Schiefer J, Miller EJ, Krenn CG, Baron DM, Faybik P: “Macrophage migration inhibitory factor as a potential predictor for requirement of renal replacement therapy after orthotopic liver transplantation.” Liver Transpl 2015, 21(5):662-669.
- Sehgal PB, Yang Y-M, Yuan H, Miller EJ: “STAT5a/b contribute to sex bias in vascular disease: A neuroendocrine perspective.” JAK-STAT 2015, 4(3):1-20.
- Linge, H. M., Ochani, K., Lin, K., Miller, E. J. “Age-Dependent Alterations in the Inflammatory Response to Pulmonary Challenge.” Immunologic Research (2015) 63, 209-15.
- Palestro,C., Linge, H.M., Nichols, K.J., Ochani,K., Bhargava,K.K., Miller, E.J. “Neutrophil Trafficking in Pulmonary Inflammation: Monitoring Migration and Blockade with 111In-Labeled Leukocytes.” J Pulm & Resp Med (2015) 5: 289
- Yang, Y. M.; Yuan, H.; Edwards, J. G.; Skayian, Y.; Ochani, K.; Miller, E. J.; Sehgal, P. B., “Deletion of STAT5a/b in vascular smooth muscle abrogates the male bias in hypoxic pulmonary hypertension in mice: implications in the human disease.” Mol Med 2015, 20 (PMID: 25470773), 625-638.
- Sehgal PB, Yang YM; Miller, EJ; “Hypothesis: neuroendocrine mechanisms (hypothalamus-growth hormone-STAT5 axis) contribute to sex bias in pulmonary hypertension.” Mol Med. 2015, 21(1):688–701.
- Linge, H. M.; Lee, J. Y.; Ochani, K.; Koga, K.; Kohn, N.; Ojamaa, K.; Powell, S. R.; Miller, E. J., “Age influences inflammatory responses, hemodynamics, and cardiac proteasome activation during acute lung injury.” Exp Lung Res 2015, 41 (4), 216-27.
- Silverman, H. A.; Dancho, M.; Regnier-Golanov, A.; Nasim, M.; Ochani, M.; Olofsson, P. S.; Ahmed, M.; Miller, E. J.; Chavan, S. S.; Golanov, E.; Metz, C. N.; Tracey, K. J.; Pavlov, V. A., “Brain Region-specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components During Peripheral Endotoxin-induced Inflammation.” Mol Med2015, 20 (1), 601-11.
- Palkar, A. V.; Agrawal, A.; Verma, S.; Iftikhar, A.; Miller, E. J.; Talwar, A., “Post Splenectomy Related Pulmonary Hypertension.” World Journal of Respirology 2015, July 28; 5(2): 69-77
- Ge, L., Trujillo,G., Miller, E.J., Kew, R.R. “Circulating Complexes of the Vitamin D Binding Protein with G-Actin Induce Lung Injury by Targeting Endothelial Cells.” Immunobiology 2014 219:198-207
- Lee, J.Y., and Miller, E.J. “Angiopoietin-2: A key to understanding sepsis and its pulmonary sequelae?” 2014 Pulmonary & Respiratory Medicine 4:172.
- Liu G, Ye X, Miller EJ, Liu SF “NF-kB-to-AP-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice.” 2014 Scientific Reports 4: 5543.
- Zaghloul,N., Patal,H., Codipilly,C., Marambaud,P. Dewey,S. Frattini,S.A., Huerta, P.T., Nasim, M.,Miller, E.J., Ahmed, M.N. “Overexpression of extracellular superoxide dismutase protects against brain injury induced by chronic hypoxia.” 2014 PLoS One 2014;9:e108168.
- Kamity, R., Patel, H., Younis,S., Nasim, M., Miller, E.J., Ahmed MN “Inhibition of CXCR 1 & 2 Delays Preterm Delivery and Reduces Neonatal Mortality in Chorioamnionitis.” (2014) European Journal of Inflammation 12;3: 447-457
- Miller, E.J. Al-Abed, Y., Zhang, Y., Cheng, K.F. “Method for treating pathologies associated with hypoxia using MIF inhibitors.” US Patent 8,741,299 Issued June 2014