Professor, Center for 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,
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
and Elmezzi Graduate School of Molecular Medicine
Phone: (516) 562-2373
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).
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.
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:
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)
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
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.
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 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.
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.
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.
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.
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.
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.
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
Field of Study: Chemistry
Northwestern University, Evanston IL
Field of Study: Chemistry
New York Medical College, Valhalla NY
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
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