Medical Student Research Fellowship for Summer 2012

Mentor: Dr. Jane G. Wigginton                 
Department: Surgery                      
Room number:G8.212       
Mail Code: 9160                  
Phone number: 214-648-8043     
E-mail: Jane.Wigginton@UTSouthwestern.edu                      
Project title: Utilization of Sex Steroids as Acute Resuscitation Drugs in Severe Traumatic Injuries                 

Human subjects IRB approved project number (where applicable): STU 022011-091, STU 022011-092

Animal subjects IRB approved project number (where applicable):  2008-0204,  2010-0272, 2011-0105

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) patient-based research and animal-based research

Brief Description of Project:
Human:
RESCUE - TBI and Shock (Resuscitative Endocrinology: Single-dose Clinical Uses for Estrogen - Traumatic Brain Injury and Hemorrhagic Shock) Pilot Trials
Numerous recent animal studies investigating the effects of sex steroids on both sexes of injured animals have overwhelmingly found estrogen to be effective at mitigating the devastating secondary injury brought about by oxidant injury, inflammation and apoptosis with up to a 65% reduction in ultimate injury for multiple different injury types. Based on these important observations, the RESCUE - TBI & Shock Trials are the first clinical studies to ever translate these animal studies to patients, by utilizing a single dose of IV estrogen as an acute resuscitation drug. It is hoped that patients with severe TBI and Hemorrhagic Shock will have a new, safe, effective therapy in the near future, based on the results of these pilot trials.

Animal:
Prior studies from our lab note that the early administration of a single dose of IV estrogen, a strong antioxidant and anti-inflammatory, decreases the severity of injury caused by early, devastating cell death, including the  remote injury seen in the brain. The present study will use adult rats given a burn injury over 40% of the total body surface area.  The rats will be sacrificed at various time points after burn injury.  Body fluids will be collected, and tissues harvested.  Laboratory studies will examine the effects a single dose of estradiol exerts on markers of injury, particularly in the brain Results from this animal study will guide the direction of pilot human studies.

The goals for the student will be to:
1. Develop an improved global understanding of human and animal research
2. Learn techniques involving human and animal specimen handling and processing for analysis
3. If desired, students will assist with all aspects of small animal injury and resuscitation models as indicated above. (Animal work is NOT required)
4. Perform basic laboratory tests, ex. ELISAs, following appropriate training
5. Experience direct patient and family member contact with research team members, which will afford them the opportunity to develop important clinical skills under the research team's guidance.
6. Participate in the screening, enrolling and consenting of patients under the research team's guidance.
7. Follow patients over time, noting changes in study outcomes, alongside our staff research coordinators
8. Participate in chart review of study patients (including collection of data, verification of diagnoses, and simple entry and analysis of data)
9. Develop skills in the areas of writing abstracts and journal articles.

Previous Research Activities or Publications with Medical Students:

Sample of Previous Published Work with Students:

  1. Lingo Lai - Non - Interventional F2-isoprostane Study - Traumatic Brain Injury (NIFTI - TBI) : Isofurans (IsoF) and F2-isoprostane (F2-IsoP) as Markers of Oxidant Injury. Abstract and Poster Winner Medical Student Research forum UTSWMC 2007
  2. Anh Nguyen - Sex Steroid Level Alterations in the Blood and CSF Following Severe Traumatic Brain Injury , Oral Presenter at the Medical Student Research Forum 2007 UTSWMC
  3. Desai PA, Gatson JW, Hynan LS, Smith JP, Idris AH, Chaudry IH, Lai LY, Wu PW,  Schatz DW, Wigginton JG. Impact of sex of lab animals on research: practice  and attitudes.  Shock, June 2009:Volume 31(7):Suppl 1:S22. Presented at the 32nd Annual North American Shock Society Meeting, June 7, 2009 in San Antonio, TX.
  4. Maass DL, Barber RC, Zang Q, Simpkins JW, Idris AH, Yi KD, Gatson JW, Goyal                         VK, Minei JD, Arnoldo BD, Wigginton JG.  Single - dose estrogen administered following severe burn injury significantly reduces circulating cytokines. Shock, June 2009:Volume 31(7):Suppl 1:S30. Presented at the 32nd Annual North American Shock Society Meeting, June 7, 2009, San Antonio, TX.
  5. Wigginton JG, Barber RC, Zang Q, Simpkins JW, Yi KD, Gatson JW, Lai LY, Lu L-   C, Minei JD, Arnoldo BD, Idris AH. Early inflammatory response in multiple  organs following severe burn injury is significantly reduced by 17β-estradiol. Shock, July 2009:123:S30.  Presented at the 32nd Annual North American Shock Society Meeting, June 7, 2009 in San Antonio, TX.
  6. Idris AH, Gatson JW, Lai L, Roberts III LJ, Minei JP, Madden CJ, Wigginton JG.  Oxidant injury occurs early after traumatic brain injury in humans:  cerebrospinal fluid isofuran and F2-isoprostane are sensitive markers of oxidant injury. Circulation, Nov 2009:120:S1466. Presented at the American Heart Association (AHA) Resuscitation Science Symposium (ReSS) 2009, November 14, 2009 in Orlando, FL.  (Selected for “Best Original Resuscitation Science”, Moderated Poster Session).