This proposal describes a five year training program for the further development of an academic career in Surgery. The principal investigator is currently a faculty member and plans to enhance her scientific skills through an unique integration of interdepartmental resources. The long term goal of this program will evaluate the effects of the neuroendocrine system on erythropoiesis following severe injury. Pranela Rameshwar, PhD will mentor the principal investigator's scientific development. Dr. Rameshwar is a recognized leader in the field of hematopoiesis, stem cells and neuroimmunology. She is an Associate Professor of Medicine and recipient of the Master Educator Award for the training of postdoctoral fellows and graduate students. To enhance this training, this program will also enlist the expertise and mentorship of David H. Livingston, MD, Professor of Surgery. Dr. Livingston has pioneered the study of bone marrow (BM) failure following trauma. Recent work in Dr. Livingston's laboratory has demonstrated that erythropoietic dysfunction occurs following trauma. Acute injury activates the neuroendocrine system and the sympathetic nervous system plays a central role in mediating the counter-regulatory stress response to injury. Sympathetic stimulation accompanies both clinical and experimental trauma as well as hemorrhagic shock and it is known to modulate erythropoiesis under non-stressed conditions. Successful erythropoiesis requires interactions between hematopoietic progenitor cells, BM stroma and the BM microenvironment. The proposed experiments will test the hypothesis that early and persistent adrenergic stimulation of BM after trauma impacts the growth of erythroid cells and contributes to the development of anemia.
The specific aims i nclude: 1) Defining alterations in erythropoiesis following modification of adrenergic stimulation, 2) Elucidating the effects of neuroendocrine manipulation on erythroid development and the cellular signaling mechanisms involved, 3) Defining the neuroendocrine effects on BM stroma and BM cytokines. In a rodent model of trauma/hemorrhagic shock with the use of both pharmacologic and surgical models of sympathetic alteration, erythropoiesis will be analyzed utilizing cellular, biochemical and molecular techniques. This proposal is novel and understanding the neuroendocrine mechanism of erythropoiesis following trauma is a preliminary step towards potential therapeutic modalities for the treatment of anemia.
| Gore, Amy V; Bible, Letitia E; Livingston, David H et al. (2015) Can mesenchymal stem cells reverse chronic stress-induced impairment of lung healing following traumatic injury? J Trauma Acute Care Surg 78:767-72 |
| Pasupuleti, Latha V; Cook, Kristin M; Sifri, Ziad C et al. (2014) Do all ?-blockers attenuate the excess hematopoietic progenitor cell mobilization from the bone marrow following trauma/hemorrhagic shock? J Trauma Acute Care Surg 76:970-5 |
| Bible, Letitia E; Pasupuleti, Latha V; Alzate, Walter D et al. (2014) Early propranolol administration to severely injured patients can improve bone marrow dysfunction. J Trauma Acute Care Surg 77:54-60; discussion 59-60 |
| Baranski, Gregg M; Pasupuleti, Latha V; Sifri, Ziad C et al. (2013) Beta Blockade Protection of Bone Marrow Following Injury: A Critical Link between Heart Rate and Immunomodulation. J Bone Marrow Res 1: |
| Pasupuleti, Latha V; Cook, Kristin M; Sifri, Ziad C et al. (2012) Does selective beta-1 blockade provide bone marrow protection after trauma/hemorrhagic shock? Surgery 152:322-30 |
| Baranski, Gregg M; Sifri, Ziad C; Cook, Kristen M et al. (2012) Is the sympathetic system involved in shock-induced gut and lung injury? J Trauma Acute Care Surg 73:343-50; discussion 350 |
| Elhassan, Ihab O; Hannoush, Edward J; Sifri, Ziad C et al. (2011) Beta-blockade prevents hematopoietic progenitor cell suppression after hemorrhagic shock. Surg Infect (Larchmt) 12:273-8 |
| Baranski, Gregg M; Offin, Michael D; Sifri, Ziad C et al. (2011) ?-blockade protection of bone marrow following trauma: the role of G-CSF. J Surg Res 170:325-31 |
| Mohr, Alicia M; ElHassan, Ihab O; Hannoush, Edward J et al. (2011) Does beta blockade postinjury prevent bone marrow suppression? J Trauma 70:1043-9; discussion 1049-50 |
| Beiermeister, Keith A; Keck, Brett M; Sifri, Ziad C et al. (2010) Hematopoietic progenitor cell mobilization is mediated through beta-2 and beta-3 receptors after injury. J Trauma 69:338-43 |
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