Clifford S. Deutschman, MS, MD

Investigator, Biomedical Science, The Feinstein Institute for Medical Research

Vice Chairman, Research, Department of Pediatrics, Cohen Children’s Medical Center, Northwell Health

Professor, Pediatrics and Molecular Medicine, Hofstra Northwell School of Medicine and Elmezzi Graduate School of Molecular Medicine

Phone: (516) 562-2373

About the Investigator

Dr. Deutschman is a graduate of Trinity College (BS), Northwestern University (MS) and New York Medical College (MD). After flirtations with surgery and neurosurgery he completed training in surgical critical care (Univ of Minnesota) and Anesthesiology (Johns Hopkins). He was on the faculty at Johns Hopkins (1988-1993) and Penn (1993-2014) as a specialist in Critical (Intensive) Care Medicine. As a member of Penn’s Department of Anesthesiology and Critical Care, he directed the Fellowship in Critical Care Medicine, the NIH-funded Research Fellowship (T32) and the Stavropoulos Sepsis Research Program. He joined Northwell Health as vice chairman of research for the Department of Pediatrics in 2014.

Dr. Deutschman has served as president of the Society of Critical Care Medicine in 2012, and the American Society of Critical Care Anesthesiologists from 2002 to 2004. He has been a permanent member of the NIH Surgery, Anesthesia and Trauma Study Section. He is scientific editor of the journal, Critical Care Medicine, and serves on the editorial boards of a number of other journals. He has been the recipient of a number of awards and honors including the Lifetime Achievement Award from the Society of Critical Care Anesthesiologists.

Dr Deutschman’s research focuses on sepsis, a common, life-threatening disorder that arises when the body’s response to infection injures its’ own tissues and organs, a topic on which he is achieved international recognition. He is one of the co-authors of the most recent version of Surviving Sepsis Campaign Guidelines and is currently co-chair of an international task force to re-examine and refine the definitions of sepsis. Dr. Deutschman has co-authored over 100 peer-reviewed publications and over 80 book chapters and editorials. He is the co-editor of the textbook Evidence-Based Practice of Critical Care (second edition to be released in 2016).

Research Focus

Dr. Deutschman’s research focuses on sepsis, a condition in which a dysregulated host response to infection leads to life-threatening organ dysfunction. Dr. Deutschman has recently become involved in some aspects of epidemiology, care delivery and health service responses in patients with sepsis.

Sepsis Pathobiology

CNS regulation of inflammation and sepsis

Collaborators: Kevin Tracey, MD; Valentin Pavlov, PhD; Patricio Huerta, PhD

Our work has shown that CLP dramatically reduces activity in a system of hypothalamic neurons that secrete the neurotransmitter orexin. The orexinergic system is a key modulator of many basic functions – respiration, cardiodynamics, temperature, appetite, arousal – and of the secretion of pituitary hormones such as TSH, ACTH, GH etc. Restoration of orexinergic activity via injection of the substance into the CSF restores sepsis-induced alterations in HR, RR, T, motor activity and pituitary hormone release. Work by Drs Tracey and Pavlov has established that another key component of sepsis, white cell activation, is also subject to CNS control, a process controlled by impulses carried to the abdominal viscera by the vagus nerve. Control of this “inflammatory reflex” is modulated by the central cholinergic system. The inflammatory reflex is impaired in sepsis. Finally, delirium is a well-described component of acute sepsis in humans, while cognitive dysfunction is prevalent in long-term survivors. Our investigations involve several components:

  • The contribution of orexinergic dysregulation to the development of dysfunction in specific organ systems. We have previously used biochemical, molecular, cellular, histologic and functional techniques to demonstrate the presence of and the mechanisms underlying sepsis-induced abnormalities in lung, liver, heart and brain. We are currently determining the role of the orexinergic nervous system in the development of these abnormalities and how manipulation of the orexinergic system effects organ dysfunction.
  • Neural pathways conducting impulses between the orexinergic centers in the lateral hypothalamus and the cholinergic nuclei in the medial septum and the lateral tegmentum. We are exploring the extent to which the interactions between these systems are altered by sepsis. We are using pharmacologic, genetic and electrophysiologic approaches.
  • We are investigating how long term survival from sepsis impairs memory, learning and homeostasis, how interactions between the cholinergic and orexinergic systems contribute and if reversal of the known defects in these systems improves abnormalities.

Sepsis – induced alterations in mitochondrial function

Collaborators: Scott Weiss (CHOP); Rick Levy (Columbia); Mervyn Singer (University College London); Lionel Blanc, PhD (Pedaitric Heme-Onc, Feinstein Institute); Lance Becker (Emergency Medicine, Northwell Health)

  • We have shown that sepsis depresses mitochondrial oxidative phosphorylation in heart and liver by interfering with the activity of electron transport chain Complex IV. We are exploring changes in other tissues and examining potential therapies, including caffeine.
  • In a project directed by Scott Weiss, MD at CHOP we are examining white cell mitochondrial function in samples obtained from septic children.
  • Dr Blanc has shown that nuclear and mitochondrial extrusion are key energy-consuming events in red blood cells. We are examining the role played by sepsis-induced mitochondrial dysfunction in the appearance of immature red cell precursors in the circulation

Sepsis-induced changes in glucocorticoid receptor isoforms (see below)

Sepsis-induced changes in cytokine signal transduction pathways (see below)

Sepsis-induced changes in metabolism

Succinate as a sepsis marker

Collaborators: Ariel Brandwein (Pediatric Critical Care Medicine); Kevin Tracey, MD

The Krebs cycle does not appear to function normally in sepsis. As a result, the intermediary succinate may leak into the cytoplasm and even out of cells. Extracellular succinate can act as a pro-inflammatory mediator, provoking cytokine activity. Dr Brandwein is measuring succinate levels in septic children to determine if serum levels of succinate are an appropriate biomarker and will correlate with the Pediatric Logistic Organ Dysfunction Score (PeLOD).

The effects of sepsis on the intracellular insulin pathway

Collaborators: Jesse Roth, MD; Ping Wang, MDKevin Tracey, MD; Phyllis Speiser, MD

Sepsis is is known to alter gluconeogenesis. We have demonstrated impaired expression of hepatic genes that encode gluconeogenic enzymes that reflects altered responses to PKA-dependent hormones such as glucagon. However, the effects of sepsis on insulin – mediated control of these genes in unknown. We are therefore examining the effects of sepsis on the insulin pathway. We believe that sepsis will attenuate these responses because insulin signal transduction involves phosphorylation, which we have shown to be impaired. In addition, we are testing the hypothesis that CNS control of glucose regulation is in part responsible for the glucose intolerance of sepsis.

Disease and treatment-induced alterations in glucocorticoid receptor isoforms

Collaborators: John Cidlowski, PhD (NIH Campus, Research Triangle, Durham NC); Phyllis Speiser MD (Endocrinology, Northwell Health); Joyce Hui-Yuen, MD (Rheumatology, Northwell Health); Beth Gottlieb MD (Rheumatology, Northwell Health); Patricio Huerta, PhD (Feinstein Institute)

Sepsis-induced changes in glucocorticoid receptor isoforms.

Sepsis alters glucocorticoid activity in a manner that often defies explanation. Newly discovered complexities in the glucocorticoid receptor, which has been shown to have a multitude of isoforms, may explain these anomalies. We are exploring changes in the relative populations of glucocorticoid isoforms in a number of different tissues in a mouse model of sepsis.

Changes in glucocorticoid receptor isoforms in patients on chronic steroid treatment.

Glucocorticoids are a standard treatment for children with asthma and inflammatory bowel disease. We are examining the effects of chronic steroid treatment on glucocorticoid receptor isoform populations and determining if changes correlate with the efficacy of treatment and/or with the development of significant side effects such as growth retardation.

Effects of steroid treatment on glucocorticoid receptor isoforms during the course of treatment.

Joyce Hui-Yuen, a Rheumatologist, is studying the effects of treatment with corticosteroids in patients Systemic Lupus Erythematosis (SLE) as their treatment progresses. In particular she is performing genomic analysis on peripheral white blood cells looking for changes in cytokine production. We are determining if this treatment alters glucocorticoid receptor isoform population and correlating these changes with treatment efficacy, co-morbidities/side effects and the expression of biomarkers.

Cytokine Signal Transduction

Sepsis-induced changes in cytokine signal transduction

Collaborators: Kevin J. Tracey, MD (Feinstein Institute)

Previous work has demonstrated that, while levels of cytokines are increased in sepsis, the signal transduction pathways are impaired. This change primarily reflects an alteration in phosphorylation, one that we believe is linked to mitochondrial dysfunction.

Anti-TNF treatment and higher neurological function

Collaborators: ) Beth Gottlieb MD (Rheumatology, Northwell Health), Joyce Hui-Yuen MD (Rheumatology, Northwell Health), Patricio Huerta, PhD (Feinstein)

It has been reported that children with chronic inflammatory disorders such as Juvenile Idiopathic Arthritis, Lupus and Inflammatory Bowel Disease who have been treated with anti-TNF antibodies develop mood alterations and anxiety and a decline in performance in school. We will use formal assessment tools to identify and quantify these changes. In addition, we are developing a mouse model of rheumatoid arthritis to explore these changes more fully.

Unique molecular delivery systems for lung disorders

Collaborators: Larry Glassman, MD (Thoracic Surgery, Northwell Health); Raphaella Sordella, PhD (Cold Spring Harbor Laboratories); Laurie Kilpatrick, PhD (Pulmonary Medicine, Temple University)

We have used adenoviral vectors and TAT, a cell-penetrating protein derived from the HIV virus, to deliver biological molecules such as HSP70 and pharmacologic agents like an inhibitor to the delta isoform of Protein Kinase C into pulmonary cells. In the past our efforts have been directed towards ling injury. However, these methods could also be used to delivery other compounds, for example, chemotherapy for lung cancer. We are in the process of initiating a new project connecting individuals at Feinstein with clinical thoracic surgery and the cancer biology experts at CSHL.

Lab Members
Mabel Abraham, PhD
Research Scientist, Director, Pediatric Analytic Research Laboratory
Research Focus: Glucocorticoid Receptors in sepsis and other disorders

Daniela Jimenez
Research Technician, Assistant Director, Pediatric Analytic Research Laboratory
Research Focus: Behavioral Changes in CLP-sepsis survivors

Ariel Brandwein, MD
Instructor in Pediatric Critical Care Medicine
Research Focus: Succinate dynamics in CLP and in septic children

Laura Novello, MD
Fellow, Pediatric Endocrinology
Research Focus: Tissue distribution of glucocorticoid receptors

Kader Cetin-Gedik, MD
Fellow, Pediatric Rheumatology
Research Focus: Behavioral changes induced by anti-TNF antibodies


Trinity College, Hartford CT
Degree: BS
Field of Study: Chemistry

Northwestern University, Evanston IL
Degree: MS
Field of Study: Chemistry

New York Medical College, Valhalla NY
Degree: MD
Field of Study: Medicine

University of Florida Teaching Hospitals, Gainesville FL
Field of Study: Surgery

University of Minnesota Hospitals, Minneapolis/St. Paul MN
Field of Study: Neurosurgery

University of Minnesota Hospitals, Minneapolis/St. Paul MN
Field of Study: Critical Care Medicine

Johns Hopkins Medical Institutions, Baltimore MD
Field of Study: Anesthesiology and Critical Care Medicine

Awards and Honors

2014 Lifetime Achievement Award, Society of Critical Care Anesthesiologists, Montreal Canada
2014 Distinguished Service Award, Society of Critical Care Medicine
2011 Critical Care Teacher of the Year, Critical Care/Trauma Fellows, University of Pennsylvania School of Medicine
2006 Critical Care Teacher of the Year, Critical Care/Trauma Fellows, University of Pennsylvania School of Medicine
2004 Winner, Leonard Berwick Award for the Teacher who best combines clinical medicine and basic science, University of Pennsylvania School of Medicine

    1. Singer M, Deutschman CS, Seymour CW, et al. “The third international consensus definitions for sepsis and septic shock (sepsis-3).” JAMA, In press
    2. Deutschman CS and Neligan PJ (eds). “An Evidence-Based Practice of Critical Care, 2nd Edition.” Philadelphia, Saunders-Elsevier, 2015.
    3. Deutschman CS, Tracey KJ. “Sepsis: current dogma and new perspectives.” Immunity. 17;40:463-75, 2014
    4. Deutschman CS, Raj NR, McGuire EO, Kelz MB. “Orexinergic activity modulates altered vital signs and pituitary hormone secretion in experimental sepsis.” Crit Care Med 41:e368-75, 2013
    5. Lyons M, Raj NN, Chittams JL, Kilpatrick L, Deutschman CS. “TAT-HSP70 attenuates experimental lung injury.” Shock 43:582-8, 2015
    6. Mondrinos MJ, Kennedy PA, Lyons M, Deutschman CS, Kilpatrick LE. “Protein kinase C and acute respiratory distress syndrome.” Shock 39:467-479, 2013
    7. Aschkenasy G, Bromberg Z, Raj NR, Deutschman CS, Weiss YG. “Enhanced Hsp70 expression protects the lung during acute lung injury by modulating apoptotic cell signaling pathways.” Plos One, 2012, 6(11):e26956. doi: 10.1371
    8. Cereda M, Emami K, Kadlecek S, Xin Y, Mongkolwisetwara P, Profka H, Barulic A, Pickup S, Mansson S, Wollmer P, Ishii M, Deutschman CS, Rizi RR. “Quantitative imaging of alveolar recruitment with hyperpolarized gas MRI during mechanical ventilation.” J Appl Physiol. 110:499-511, 2011
    • Kilpatrick LE, Standage SW, Li H, Raj NR, Korchak HM, Wolfson MR, Deutschman CS. “Protection against sepsis-induced lung injury by selective inhibition of protein kinase C-delta (delta-PKC).” J Leukoc Biol 89:3-10, 2011
    1. Verma R, Huang Z, Deutschman CS, Levy RJ. “Caffeine restores myocardial cytochrome oxidase activity and Improves cardiac function during sepsis.” Crit Care Med, 37:1397-402, 2009
    2. Abcejo AS, Andrejko KM, Raj NN, Deutschman CS. “Failed interleukin-6 signal transduction in murine sepsis: attenutation of hepatic glycoprotein (gp) 130 phosphorylation.” Crit Care Med, 37:1729-1734, 2009
    3. Levy RJ, Deutschman CS. “Cytochrome c oxidase dysfunction in sepsis.” Crit Care Med, 35:S468-S475, 2007
    4. Weiss YG., Bromberg Z, Raj N, Raphael J, Goloubinoff P, Ben- Neriah Y, Deutschman CS. “Enhanced Hsp70 expression alters IB kinase proteasomal degradation in experimental acute respiratory distress syndrome.” Crit Care Med 35:2128-2138, 2007
    5. Deutschman CS, Ochroch EA, Cereda M, Raj N. “Sepsis-Induced Cholestasis, steatosis, hepatocellular injury and impaired hepatocellular regeneration are enhanced in IL-6.” Crit Care Med 34:2613-2621, 2006
    6. Weiss YG, Maloyan A, Tazelaar J, Raj N, Deutschman CS. “Adenoviral transfer of HSP-70 into the pulmonary epithelium improves histology and outcome in experimental acute respiratory distress syndrome.” J. Clin. Invest 110: 801-806, 2002

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