Medical Student Research Fellowship for Summer 2010

Mentor: John Teiber
Department: Internal Medicine
Room number: Y7.216
Mail Code: 8874
Phone number: 214-648-2454
E-mail: john.teiber@utsouthwestern.edu
Project title: Characterization of PON2 expression and activity in primary mouse microglia.
Human subjects IRB approved project number (where applicable): Not applicable

Animal subjects IRB approved project number (where applicable): Not applicable

Project Type: Basic Research

Brief Description of Project: PON2 is an intracellular membrane-associated esterase that has uncertain physiological functions. It protects cells from oxidative and endoplasmic reticulum stress and is also up-regulated by such stressors, although its antioxidative mechanism is unknown. In macrophages, PON2 protects the cells, as well as LDL added to the cultures, from oxidative damage and also attenuates macrophage inflammatory responses after cellular activation. PON2 attenuates atherosclerosis in mouse models and this is thought to be at least partly due to its antioxidant/anti-inflammatory effects in macrophages. The goal of this project is to characterize the expression of PON2 in microglia, CNS-resident macrophages, to lay the groundwork for determining the role PON2 may play in protecting the CNS from oxidative stress and neuroinflammation. The student will first isolate and culture microglia from adult mouse brains using established procedures. The brains will be obtained from my colleague, Dr. Sinton, from mice utilized for unrelated studies immediately post-euthanasia. The levels of PON2 activity and protein expression in the microglia will then be assessed. Then the student will determine if PON2 activity and expression is altered in cultures by oxidative stress, pro-inflammatory mediators and endoplasmic reticulum stress.

Previous Research Activities or Publications with Medical Students:
Last summer two first year medical students worked in my laboratory under my supervision. Kelly Tornow assessed the levels of PON2 activity and protein in spinal chord homogenates from a mouse amyotrophic lateral sclerosis (ALS) model and demonstrated that PON2 is up-regulated in the ALS mouse spines. Some of Kelly's data will be included in our forthcoming manuscript. Aimee Lam was hired to process blood from Gulf War veterans for our large epidemiology study in which paraoxonase 1 status in ill and well veterans was determined. Aimee also was trained to genotype PON1 and she genotyped a large number of the samples.