Dr. Dezfulian is an adult and pediatric critical care physician acutely aware of the paucity of post-resuscitation therapies for the cardiac arrest survivors he cares for. This career development award supplements his research background with senior mentorship and lab-based and didactic training in neurosciences and redox signaling. The research plan is based on preliminary observations which support the hypothesis that nitrite-mediated neuroprotection after cardiac arrest occurs through nitric oxide (NO) and S-nitrosothiol (S-NO)-based signaling that prevents subsequent neuronal death by targeting delta protein kinase C and mitochondria. This hypothesis will be tested along three aims: (1) to define the optimal nitrite dose and timing and quantify the relative contributions of NO- and S-NO based signaling in neuroprotection, (2) to test whether nitrite-mediated neuroprotection results from nitrosylation and inactivation of delta protein kinase C (-PKC), and (3) to test whether nitrite-mediated NO and S-NO production affects mitochondrial function and prevents apoptosis. Dr. Dezfulian will undertake a career development plan consisting of: 1. Experimental research, laboratory instruction, journal clubs and scientific review and development by his mentors and colleagues. 2. Coursework through the University of Miami graduate program. 3. Intramural seminars and national conferences and symposia. 4. Training in the responsible conduct of research. 5. Guidance by a scientific advisory committee consisting of two senior MDs and two PhDs. 6. Grant writing, grant review and development of a transition plan aimed at independence. Dr. Dezfulian's neuroscience mentorship will primarily come from Dr. Miguel Perez-Pinzon, CVDRC director. Dr. Perez-Pinzon is an accomplished NIH-funded neuroscientist who studies mechanisms of neuroprotection and mitochondrial dysfunction after brain ischemia. Dr. Dezfulian will be co-mentored by Dr. Joshua Hare, Director of the Interdisciplinary Stem Cell Institute (ISCI). Dr. Hare is NIH-funded to investigate oxidative stress in heart failure, has a long track record of research in nitroso-redox signaling, and will provide guidance regarding key mechanistic pathways believed to underlie nitrite mediated neuroprotection. This mentorship team will guide Dr. Dezfulian's career development as he executes the research aims of this application and transitions to independence as a clinician scientist.

Public Health Relevance

This career development awards provides Dr. Cameron Dezfulian, an intensive care unit physician, with salary and research support to pursue a career development plan aimed at making him an independent clinician scientist studying ways to reduce brain injury after cardiac arrest. Dr. Dezfulian will be mentored by two senior scientists at the University of Miami and conduct research aimed at discovering new ways to signal protection in brain after cardiac arrest to prevent the brain injury that normally results.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Clinical Investigator Award (CIA) (K08)
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Study Section
NST-2 Subcommittee (NST)
Program Officer
Koenig, James I
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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Uray, Thomas; Lamade, Andrew; Elmer, Jonathan et al. (2018) Phenotyping Cardiac Arrest: Bench and Bedside Characterization of Brain and Heart Injury Based on Etiology. Crit Care Med 46:e508-e515
Dezfulian, Cameron; Olsufka, Michele; Fly, Deborah et al. (2018) Hemodynamic effects of IV sodium nitrite in hospitalized comatose survivors of out of hospital cardiac arrest. Resuscitation 122:106-112
Dezfulian, Cameron; Taft, Maia; Corey, Catherine et al. (2017) Biochemical signaling by remote ischemic conditioning of the arm versus thigh: Is one raise of the cuff enough? Redox Biol 12:491-498
Janiczek, Jonathan A; Winger, Daniel G; Coppler, Patrick et al. (2016) Hemodynamic Resuscitation Characteristics Associated with Improved Survival and Shock Resolution After Cardiac Arrest. Shock 45:613-9
Dezfulian, Cameron; Kenny, Elizabeth; Lamade, Andrew et al. (2016) Mechanistic characterization of nitrite-mediated neuroprotection after experimental cardiac arrest. J Neurochem 139:419-431
Elmer, Jonathan; Scutella, Michael; Pullalarevu, Raghevesh et al. (2015) The association between hyperoxia and patient outcomes after cardiac arrest: analysis of a high-resolution database. Intensive Care Med 41:49-57
Jentzer, Jacob C; Chonde, Meshe D; Dezfulian, Cameron (2015) Myocardial Dysfunction and Shock after Cardiac Arrest. Biomed Res Int 2015:314796
Kochanek, Patrick M; Dezfulian, Cameron (2015) Asphyxial cardiac arrest from drowning: giving E-CPR the cold shoulder. Resuscitation 88:A7-8
Coppler, Patrick J; Elmer, Jonathan; Calderon, Luis et al. (2015) Validation of the Pittsburgh Cardiac Arrest Category illness severity score. Resuscitation 89:86-92
Uray, Thomas; Mayr, Florian B; Fitzgibbon, James et al. (2015) Socioeconomic factors associated with outcome after cardiac arrest in patients under the age of 65. Resuscitation 93:14-9

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