Edmund Miller, PhD CChem CSci FRSC

Professor, The Merinoff Center for Patient-Oriented Research, The Feinstein Institute for Medical Research

Director, Cardiopulmonary Research Laboratory, The Feinstein Institute for Medical Research

Professor, Medicine & Molecular Medicine & Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell

Phone: (516) 562-1637
Email: emiller@northwell.edu

About the Investigator

Dr. Edmund Miller started his career in science in the pathology department at Kings College Hospital in 1972. He worked there for 14 years, leaving in 1986 as chief medical laboratory scientific officer. During that time, 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 1986, Dr. Miller joined the research group of Dr. Allen Cohen at the University of Texas Health Center in Tyler, Texas, as a postdoctoral fellow. Their research focused on acute lung injury, and they were the first to define interleukin-8 as a major neutrophil chemotaxin in acute respiratory distress syndrome.

Subsequently, they designed and patented a series of specific small molecules to block the effects of interleukin-8, stopping movement and activation of these white cells to reduce their harmful effects. They also showed that these molecules could stop the growth and metastasis of several forms of cancer cells, including melanoma and adenocarcinoma.

In 1998, Dr. Miller was admitted to the Royal Society of Chemistry as a fellow, the highest class of membership. In 2001, he left the University of Texas and joined Northwell Health in New York as chief of surgical research. During his years in New York, he has focused on acute lung injury associated with bacterial infections and pulmonary hypertension.

In 2006, he was appointed associate professor of surgery at Albert Einstein College of Medicine; scientific advisor, Shandong Academy of Sciences, Jinan, PR China; and associate professor, Elmezzi Graduate School of Molecular Medicine.

He is currently professor of the Merinoff Center for Patient-Oriented 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.

Research Focus

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. 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.

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. 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 findings 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 Hypertension

Pulmonary arterial hypertension (PAH) is a chronic progressive disorder that leads to remodeling of blood vessels in the lung, low oxygen in the blood, right-sided heart failure and death. The disorder is also associated with anxiety, cognitive dysfunction and depression. PAH 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%. 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.

Lab Members

Ke Lin
Sr Research Assist

Kanta Ochani
Post Doc Res Fellow(RI)(GF)

Ping Wang MS
Senior Research Assistant

Education

North East Thames Polytechnic, London, UK
Degree: BSc (honors)
1977-1980
Field of Study: Applied biology

Thames Polytechnic, London, UK
Degree: MSc
1980-1983
Field of Study: Analytical chemistry

King’s College, London University, UK
Degree: PhD
1984-1989
Field of Study: Biochemistry

Awards & Honors

2017 Appointed to the Education Board at the American Health Council
2013 Zhejiang West Lake Friendship Award for Foreign Experts, Awarded by the People’s Government of Zhejiang Province, P.R. China
2006 Appointed Scientific Advisor, Shandong Academy of Sciences, Jinan, PR China
1998 Elected Fellow of The Royal Society of Chemistry (CChem FRSC)
1994 Parker B. Francis Fellow in Pulmonary Research

Publications
  1. Miller, E.J., Linge, H.M. “Age related changes in immunological and physiological responses following pulmonary challenge.” International Journal of Molecular Sciences 2017, 18, 1294-1304 Special Edition: Immunology of Aging
  2. Baron-Stefaniak, J., Schiefer, J. Miller, E.J., Berlakovich,G., Baron,D.M., Faybik, P.”Comparison of macrophage migration inhibitory factor and neutrophil gelatinase-associated lipocalin-2 to predict acute kidney injury after liver transplantation: An observational pilot study.” PLOS ONE Aug 15, 2017
  3. Szema,A., Mirsaidi,N., Burns, M.P. M., McClain, S.A., Forsyth, E., Li, J B., Dukes, B., Lina, D., Nahvi, R., Jheison G., Patton, M., Wang, P., Lin, K., Miller, E.J., Ratliff, T., Crist, S., Takemaru, K-I. “Enhanced mortality to metastatic bladder cancer cell line MB49 in Vasoactive Intestinal Peptide (VIP) gene knockout mice.” Frontiers in Endocrinology, 2017 August 07; 8:162
  4. Baron-Stefaniak, J., Schiefer, J. Miller, E.J., Plöch, W., Krenn, C.G., Berlakovich,G., Baron, D.M., Faybik, P. “Liver graft-derived and serum MIF reflect hepatocellular injury in patients undergoing orthotopic liver transplantation.” Clinical Transplantation       2017;31:e12982
  5. Cagliani, J., Grande, D., Molmenti, E., Miller, E.J., Rilo, H. “Immunomodulation by mesenchymal stromal cells and their clinical applications.” J. Stem Cell & Regenerative Biology 2017 3(2): 1-14
  6. Bruchfeld, A., Wendt,M., Miller, E.J. “Macrophage migration inhibitory factor (MIF) in Chronic Kidney Disease.” Frontiers in Immunology   2016 26;7: 8,1-7
  7. Olofsson, P. S.; Oswald, M.; Ahmed, M. N.; Hanes, W.; Steinberg, B. E.; Lu, B.; Dancho, M.; Rosas-Ballina, M.; Hudson, L. K.; Valdes-Ferrer, S. I.; Holodick, N. E.; Bloom, O.; Stiegler, A.; Liu, S. F.; Pavlov, V. A.; Chavan, S. S.; Andersson, U.; Diamond, B.; Miller, E.J.; Arner, A.; Gregersen, P. K.; Back, P.; Mak T.W.; Tracey, K. J. “Choline acetyltransferase+ T lymphocytes regulate vascular endothelial derived relaxing factor.” Nature Biotechnology 2016 Sep 12. doi: 10.1038/nbt.3663.
  8. 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 Sep 1:1-12.
  9. 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.
  10. 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 One 2016, 11(6):e0157837.
  11. Bruchfeld A, Wendt M, Miller EJ: “Macrophage Migration Inhibitory Factor in Clinical Kidney Disease.” Front Immunol 2016, 7:8.
  12. 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.
  13. 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.
  14. 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.
  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
  16. 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.
  17. 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.
  18. 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.
  19. 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 Med 2015, 20 (1), 601-11.
  20. 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

Patent:

  1. Miller, E.J. Al-Abed, Y., Zhang, Y., Cheng, K.F. “A method for treating a neurological disorder associated with hypoxia, using a small molecule MIF inhibitor.” US 9457013 Issued: Oct 4, 2016
  2. 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
  3. Miller,E.J., & Hayashi,S. “Peptide tumor cell growth inhibitors.” Patent 6,355,619 Issued Mar 2002
  4. Miller,E.J., & Hayashi,S. “Peptide tumor cell growth inhibitors.” Patent 6,110,889 Issued Aug 2000
  5. Cohen,A.B., Miller,E.J., Kurdowska,A.K., Hayashi,S., Tuttle,R. “Methods of inhibiting CXC intercrine molecules.” Patent 5,965,536 Issued Oct 1999
  6. Cohen,A.B., Miller,E.J., Nagao,S., Carr,F.K. “Peptide inhibitors of neutrophil activating factor induced chemotaxis.” Patent 5,079,228 Issued Jan 1992

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