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Basic Science & Clinical Research

Lab outside

Mission

The UC San Diego Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery Research Laboratory is focused on studying the injury response.  Our research group consists of an integrated team of surgeon-scientists and PhD researchers who share a common goal of performing cutting-edge basic science and translational studies.  We strive to perform “bench to bedside” research by utilizing cellular, molecular, and genetic techniques to better understand the injury response with the goal of improving outcomes in patients following severe trauma and burn.

Lab activities

Research activities of the Division of Trauma, Surgical Intensive Care and Burn are organized into two research teams:

  • Basic Science Research Team
  • Clinical Research Team

*Published articles of Basic Science and Clinical Research from 1984 to 2012

 

Basic Science Research Team

A. Baird
A. Baird
X. Dang
X. Dang
B.Eliceiri
B.Eliceiri
E. Amburn
E. Amburn

A. Hageny
A. Hageny
J. Lee
J. Lee
J. Putnam
J. Putnam

 

Investigators

 

Diseases/Research Topics

1) Sentinel Genes in Trauma/Burn

In an era where sequencing of the human genome, and the genomes of many other species have been identified, the challenge remains: What genes are biomarkers of severe trauma and burn injury, and secondly, is there a functional role for these genes? We have focused on bioinformatic mining techniques in human leukocytes to identify and characterize orphan genes (i.e. genes with no known function) that encode ligands/peptide hormones.  Here, our goal is to use such techniques to identify biomarkers and functional gene products that can be used to better understand the pathophysiology of multiple organ failure in trauma/burn patients.  To this end, we have recently identified one such gene, Ecrg4, which encodes a membrane-anchored peptide, which is released upon injury, as a specific example of a gene that we de-orphanized with these techniques and has both clinical relevance and a functional role in the innate immune response. 

 

  • Publication Highlights
    • Gonzalez AM, Podvin S, Lin S, Miller MC, Botfield H, Leadbeater WE, Roberton A, Dang X, Knowling SE, Cardenas-Galindo E, Donahue JE, Stopa EG, Johanson CE, Coimbra R, Eliceiri BP, Baird A. Ecrg4 expression and its product augurin in the choroid plexus: impact on fetal brain development, cerebrospinal fluid homeostasis and neuroprogenitor cell response to CNS injury. Fluids Barriers CNS 2011 Jan 18;8(1):6. PMCID: PMC3042980
    • Podvin S, Gonzalez AM, Miller MC, Dang X, Botfield H, Donahue JE, Kurabi A, Boissaud-Cooke M, Rossi R, Leadbeater WE, Johanson C, Coimbra R, Stopa EG, Eliceiri BP, Baird A. Esophageal cancer related gene-4 is a choroid plexus-derived injury response gene: evidence for a biphasic response in early and late brain injury. PLoS One 2011 6(9):e24609. PMCID: PMC3173480
    • Baird A, Coimbra R, Dang X, Lopez N, Lee J, Krzyzaniak M, Winfield R, Potenza B, Eliceiri BP. Cell surface localization and release of the candidate tumor suppressor Ecrg4 from polymorphonuclear cells and monocytes activate macrophages. J Leukoc Biol 2012 May;91(5):773-81. PMCID: PMC3336773
    • Dang X, Podvin S, Coimbra R, Eliceiri B, Baird A. Cell-specific processing and release of the hormone-like precursor and candidate tumor suppressor gene product, Ecrg4. Cell Tissue Res 2012 Jun;348(3):505-14. PMCID: PMC3367106
    • Shaterian A, Kao S, Chen L, di Pietro L, Coimbra R, Eliceiri BP, Baird A. The candidate tumor suppressor gene Ecrg4 as a wound terminating factor in cutaneous injury. Arch Dermatol Res 2012 Aug 17, Epub ahead of print.

 

2) Modulating Shock/Burn-induced organ injury through the nervous system

The capacity for the vagus nerve to regulate immune-homeostasis has been a focus of laboratory studies based on the significant insights into how stimulation of the vagus nerve can mediate the inflammatory setpoint in injury. Injury setpoint refers to the systemic inflammatory status either pre-/post-injury or during the course of care that may alter the immune response and account for different outcomes between individuals who suffer similar injuries. Studies in our laboratory have defined the ability of vagal nerve stimulation (VNS) to prevent intestinal inflammation and improve gut epithelial barrier function after injury. Intestinal inflammation following injury has previously been defined as the catalyst for the systemic inflammatory response to injury that can lead to organ failure and late deaths in injured patients. Our studies have identified enteric glia cells, a component of the enteric nervous system, as a candidate cell type that may mediate the gut protective effects of VNS. By harnessing the anti-inflammatory effects of enteric glia cell activation, we hope to develop therapeutics that may improve outcomes in patients following severe trauma and burn injury. 

 

  • Publication Highlights
    • Costantini TW, Krzyzaniak M, Cheadle GA, Putnam JG, Hageny AM, Lopez N, Eliceiri BP, Bansal V, Coimbra R. Targeting α-7 nicotinic acetylcholine receptor in the enteric nervous system: A cholinergic agonist prevents gut barrier failure after severe burn injury. Am J Pathol 2012 Aug;181(2):478-86. Epub 2012 Jun 8.
    • Costantini TW, Bansal V, Krzyzaniak MJ, Putnam JG, Peterson CY, Loomis WH, Wolf PL, Baird A, Eliceiri BP, Coimbra R. Vagal nerve stimulation protects against burn-induced intestinal injury through activation of enteric glia cells. Am J Physiol Gastrointest Liver Physiol 2010 Dec;299(6):G1308-18. Epub 2010 Aug 12.
    • Lopez NE, Krzyzaniak M, Costantini TW, De Maio A, Baird A, Eliceiri BP, Coimbra R. Vagal Nerve Stimulation Blocks Peritoneal Macrophage Inflammatory Responsiveness After Severe Burn Injury. Shock 2012 Aug;38(3):294-300. PMCID: PMC3422402.
    • Krzyzaniak MJ, Peterson CY, Cheadle G, Loomis W, Wolf P, Kennedy V, Putnam JG, Bansal V, Eliceiri B, Baird A, Coimbra R. Efferent vagal nerve stimulation attenuates acute lung injury following burn: The importance of the gut-lung axis. Surgery 2011 Sept; 150(3):379-89. Epub 2011 Jul 23.
    • Costantini TW, Bansal V, Peterson CY, Loomis WH, Putnam JG, Rankin F, Wolf P, Eliceiri BP, Baird A, Coimbra R. Efferent vagal nerve stimulation attenuates gut barrier injury after burn: modulation of intestinal occludin expression. J Trauma 2010 Jun;68(6):1349-54; discussion 1354-6.
    • Lopez N, Krzyzaniak M, Chelsea B, Ortiz-Pomales Y, Hageny AM, Eliceiri B, Coimbra R, Bansal V. Ghrelin prevents disruption of the blood brain barrier after traumatic brain injury. Journal of Neurotrauma 2012 Jan 20;29(2):385-93. Epub 2011 Oct 26.

 

3) Blood Brain Barrier in Injury, Inflammation and Vascular Normalization

The blood brain barrier (BBB) is well-known for its capacity to limit access of to the brain from the circulation. Our BBB research projects are focused on the three main areas. First, we are evaluating the peptide hormone ghrelin and VNS as anti-inflammatory strategies that protect from traumatic brain injury (TBI)-induced neurological deficits and breakdown of the BBB. Second, we are examining Ecrg4 as a mediator of microglia activation and neuroepithelial integrity in glioma and penetrating brain injury. Third, we are characterizing the mechanism and preclinical relevance of vascular normalization using genetic models or pharmacological inhibitors of focal adhesion kinase. In combination, these studies provide a integrated approach for the study of BBB integrity to better understand mechanisms that regulate immune and vascular homeostasis.

 

  • Publication Highlights
    • Lund CV, Nguyen MTN, Owens GC, Pakchoian AJ, Shaterian A, Kruse CA, Eliceiri BP. Reduced glioma infiltration in Src-deficient mice. J Neurooncol 2006 May;78(1):19-29. Epub 2006 Mar 22.
    • Bansal V, Costantini TW, Kroll L, Peterson CY, Loomis WH, Putnam JG, Eliceiri BP, Baird A, Coimbra R. Traumatic brain injury and intestinal dysfunction: uncovering the neuro-enteric axis. J Neurotrauma 2009 Aug;26(8):1353-9. PMCID: PMC2989839
    • Lee J, Lund-Smith C, Borboa A, Gonzalez AM, Baird A, Eliceiri BP. Glioma-induced remodeling of the neurovascular unit. Brain Res 2009 Sep 8;1288:125-34. PMCID: PMC2735571.
    • Bansal V, Ryu SK, Blow C, Costantini T, Loomis W, Eliceiri BP, Baird A, Wolf P, Coimbra R. The Hormone Ghrelin Prevents Traumatic Brain Injury Induced Intestinal Dysfunction. J Neurotrauma 2010 Dec;27(12):2255-60. PMCID: PMC3304249.
    • Lee J, Borboa A, Chun HB, Baird A, Eliceiri BP. Conditional deletion of the focal adhesion kinase FAK alters remodeling of the blood-brain barrier in glioma. Cancer Res 2010 Dec 15;70(24):10131-40. PMCID: PMC3059220.
    • Lee J, Borboa AK, Baird A, Eliceiri BP. Non-invasive quantification of brain tumor-induced astrogliosis. BMC Neurosci 2011 Jan 19;12(1):9. PMCID: PMC3033849.
    • Lopez N, Krzyzaniak M, Chelsea B, Ortiz-Pomales Y, Hageny AM, Eliceiri B, Coimbra R, Bansal V. Ghrelin prevents disruption of the blood brain barrier after traumatic brain injury. Journal of Neurotrauma 2012 Jan 20;29(2):385-93. Epub 2011 Oct 26.
    • Lopez NE, Krzyzaniak MJ, Costantini TW, Putnam J, Hageny AM, Eliceiri B, Coimbra R, Bansal V. Vagal nerve stimulation decreases blood-brain barrier disruption after traumatic brain injury. J Trauma Acute Care Surg 2012 Jun;72(6):1562-6.

 

Clinical Research Team

T. Curry
T. Curry
E. Trinidad
E. Trinidad
M. Tyler
M. Tyler

 

The Division has a very active and vibrant group of research staff who participate with the faculty in multiple clinical projects, including federally funded and industry sponsored clinical trials in trauma, burns, surgical critical care, and wounds. In addition, several clinical trauma registry-based studies focusing on epidemiology, quality improvement, outcomes, and injury prevention are ongoing.

Active Division of Trauma Research (as of April 2, 2010)

Elderly with Closed Head Injuries on Anti-Coagulants database review - delineation of our experience with elderly trauma patients taking medications that affect coagulation.

Immune Studies in SICU prospective blood collection - study of various immune system components in hospitalized patients in traumatic shock or sepsis

Lower Extremity Blast Injury database review – comparison of outcomes for open tibia fractures: US military combat vs. US level 1 trauma center

Trauma in the Elderly database review – identification of epidemiologic patterns in mechanism and severity of injury and outcomes in the elderly

Computerized Glycemic Control database review – an evaluation of the blood glucose control algorithm utilized on in-patients at UCSD Medical Center

Craniectomy medical record review – evaluation of the effectiveness of decompressive craniectomy on patient outcomes

Immune Studies prospective blood collection - a study of various immune components of normal human blood

INTRuST TBI/PTSD Consortium consent of human subjects – a brain MRI of healthy volunteers to calibrate the functional MRI scanner for use in future consortium research studies (http://intrust.ucsd.edu/)

Open Abdomen medical record review – seeks to determine independent predictors of failure to achieve primary closure of an open abdomen during the initial hospitalization following trauma

Preventable Deaths database/medical record review – a review of preventable deaths, errors and delays causing mortality in a Level I Trauma Center

Retained Hemothorax medical record review – seeks to determine the predictors of the need for thoracotomy in the treatment of retained hemothorax following trauma.

Progesterone in Severe Traumatic Brain Injury commercial sponsor – to determine the efficacy and safety of i.v. progesterone utilizing in severe traumatic brain injury patients

Commercial Sponsor- Healthpoint A Phase II Randomized, Double Blind, Placebo Controlled Dose Finding Study Investigating the Efficacy of HP802-247 in Venous Leg Ulcers

Investigator Initiated A Single-Center, Randomized Study of Nexagon® for the Treatment of Inflammatory Lower Extremity Leg Wounds

Commercial Sponsor-Synovis Orthopedic & Woundcare The Mechanism of Action of Unite™ Biomatrix in Diabetic Foot Ulcer

Commercial Sponsor-US Biotest The Mechanism of Action of Unite™ Biomatrix in Diabetic Foot Ulcer