Medical Student Research Fellowship for Summer 2008
Mentor: Zhi-Ping Liu
Department: Internal Medicine-Cardiology division
Project title: Role of Foxo4 in inflammatory bowel disease
Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable):
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) Animal-based and basic research.
Brief Description of Project:
Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a complex group of chronic inflammatory disorders of the gastrointestinal tract that affect more than one million individuals in the United State and several millions worldwide. The cause(s) of IBD remains unknown. However, it is widely believed that the disease arises from an excessive immune response to normal gut bacteria and food antigens due to one or more genetically determined defects. The disease is driven by a robust overproduction of cytokines. Cytokines are small peptide proteins produced by immune cells that facilitate communication between cells, stimulate the proliferation of antigen-specific effector cells, and promote inflammation. Cytokines are produced mainly through gene activation by a key molecule, NF- B. We have recently found that the ability of NF- B to activate inflammatory gene expression can be repressed by FoxO4, a molecule that regulates expression of certain genes in the cell. The ability of FoxO4 to inhibit NF- B may be physiologically important since mice lacking Foxo4 have elevated levels of certain inflammatory cytokines in the gut and they are more susceptible to develop 2,4,6-trinitrobenzene sulfonic acid-induced colitis, a mouse model for Crohn's disease. In the studies proposed here, we will identify the cause and cellular element(s) that underlie the elevated cytokine expression in mice lacking Foxo4 using fluorescent activated cell sorting and the minimal interactive domain(s) between FoxO4 and NF- B using co-immunoprecipitation and GST-pull down assays.
Previous Research Activities or Publications with Medical Students:
Gonzalo Barraza has participated in a cDNA screen to identify molecule(s) involved
in regulation of the transcription of FoxO4 in the summer of 2007.