Genetic Risk for Pulmonary Injury in Sepsis

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Educational Immersion Experience Title: Genetic Risk for Pulmonary Injury in Sepsis
Mentor(s): Timothy Buchman, Ph.D., M.D., and Barbara Zehnbauer, Ph.D.
Location: S. Kingshighway Building
Educational goals:
1) Understand the importance of associations of polymorphisms in candidate genes or candidate gene
pathways with predisposition to sepsis-associated, adverse pulmonary outcomes
2) Understand methods that employ both human and murine systems to study genetic predisposition to
inflammatory airway disease during and after sepsis
Weeks 1-3:
Participate in laboratory meeting (1 hour/week)
Select candidate gene or candidate gene pathway to study pulmonary outcome of sepsis;
identify murine vs. human system (6 hours/week)
Meet with Drs. Buchman and Zehnbauer (1 hour/week)
Weeks 3-6: Participate in laboratory meeting (1 hour/week)
Participate in experimental approach development and performance of murine experiments (4
hours/week)
Begin analysis of human data (2 hours/week)
Meet with Drs. Buchman and Zehnbauer (1 hour/week)
Weeks 7-9: Participate in laboratory meeting (1 hour/week)
Preliminary analysis of murine experiments(3 hours/week)
Continue analysis of human data (3 hours/week)
Meet with Drs. Buchman and Zehnbauer (1 hour/week)
Weeks 10-12: Participate in laboratory meeting (1 hour/week)
Complete analysis of murine and/or human data (6 hours/week)
Present one hour seminar concerning association of candidate gene variation and severity of
sepsis-associated pulmonary disease (1 hour/week)
Meet with Drs. Buchman and Zehnbauer (1 hour/week)
Suggested reading(s):
Vyas D, et al. Epithelial apoptosis in mechanistically distinct methods of injury in the murine small intestine.
Histology & Histopathology. 22(6):623-30, 2007
Freeman BD, et al. Genetic research and testing in critical care: surrogates' perspective. Critical Care
Medicine. 34(4):986-94, 2006
Chung TP, et al. Molecular diagnostics in sepsis: from bedside to bench. Journal of the American College of
Surgeons. 203(5):585-598, 2006
Husain KD, et al. Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine
acute lung injury. Critical Care Medicine. 33(10):2350-7, 2005
Wizorek JJ, et al. Sequence makes a difference: paradoxical effects of stress in vivo. Shock. 22(3):229-33,
2004
Saleh M, et al. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms.
Nature. 429(6987):75-9, 2004
Tabrizi AR, et al. Genetic markers in sepsis. Journal of the American College of Surgeons. 192(1):106-17,
2001
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