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Lou Ann Brown. Pediatrics.
Phone: 404-727-5739
Email: lbrow03@emory.edu
Institution: Emory
Location: On Campus (Emory main campus)
Availability: Spring,Summer,Fall
Lab Positions: 2
Project Description: Background: Alcohol abuse has significantly increased in women of childbearing age resulting in a large population of premature infants with fetal alcohol exposure. Alcohol-induced oxidant stress and damage is best described in the developing brain, however, all developing organ systems are exposed to alcohol-induced oxidative stress. We have shown that maternal alcohol abuse increased the risk of early onset sepsis in the very low birth weight premature neonate. In utero exposure to pro-inflammatory cytokines increases the risk of adverse outcomes in the premature newborn such as chronic lung disease and sepsis. Bronchopulmonary dysplasia (BPD) results from chronic intrauterine exposure to pro-inflammatory cytokines that primes the fetal lung so that minimally injurious postnatal events provoke an exuberant pulmonary inflammatory response and potentiates lung injury.
In adults, chronic alcohol abuse depletes the antioxidant glutathione (GSH), induces chronic oxidant stress and a chronic pro-inflammatory state. This subsequently results in an exaggerated response to a second hit such as sepsis or trauma. As observed in adults, we do not believe that fetal alcohol exposure alone causes BPD. Rather, we postulate that alcohol-induced fetal GSH depletion results in a chronic pro-inflammatory state that places the very premature lung at a greater risk for injury when a second hit occurs. In animal models of in utero alcohol exposure, we are exploring fetal lung GSH depletion, chronic oxidant stress and a chronic pro-inflammatory state that subsequently delays lung maturation and increases the risk of lung injury when there is premature delivery. Furthermore, we propose that GSH precursors will attenuate that injury when given after delivery.
Student Requirements: Juniors and seniors only
Accepts 2nd year students? Y
Suggested Reading (References):
(1) T.W. Gauthier, X.D. Ping, F.L. Harris, M. Wong, H. Elbahesh, and L.A.S. Brown. Fetal alcohol exposure impairs alveolar macrophage functions via decreased glutathione availability. Pediatr. Res. 57: 76-81 (2005).
(2) L.A.S. Brown, F.L. Harris, X.-D. Ping and T.W. Gauthier. Chronic ethanol ingestion and the risk of acute lung injury: a role for glutathione availability? Alcohol 33: 191-197 (2004).
(3) M.H. Manar, M.R. Brown, T.W. Gauthier, and L.A.S. Brown. Association of glutathione-S-transferase P1 (GST-P1) polymorphisms with bronchopulmonary dysplasia. J. Perinatol. 24: 30-35 (2004).
(4) A. Pelaez, R.I. Bechara, P.C. Joshi, L.A.S. Brown and D.M. Guidot. Granulocyte/macrophage colony-stimulating factor treatment improves alveolar epithelial barrier function in alcoholic rat lung. Am. J. Physiol. (Lung Cell Mol. Physiol.) 286: L106-L111 (2004).
Techniques used in this lab: Fluorescent microscopy; confocal microscopy; real time PCR; western blot analysis
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Nael McCarty. Pediatrics.
Phone: 727-3654
Email: namccar@emory.edu
Institution: Emory
Location: On Campus (Emory main campus)
Availability: Summer
Lab Positions: 1
Project Description: Our lab has identified a peptide toxin inhibitor of CFTR, the chloride channel protein defective in Cystic Fibrosis. The summer project would entail the production of mutant forms of this toxin, which we call GaTx1, and performance of electrophysiological experiments to test the efficacy of inhibition by the mutant toxins. Students will learn: molecular biology, recombinant protein production, electrophysiology.
Student Requirements: Rising junior at least, having completed basic biology courses and had some wet lab experience.
Accepts 1st year students? Y
Accepts 2nd year students? Y
Suggested Reading (References):
(1) 25) Fuller, M.D., C.H. Thompson, Z.-R. Zhang, C. Freeman, B. Sarkadi, G. Szakacs, D. McMaster, R.J. French, J. Pohl, J. Kubanek, and N.A. McCarty (2007) State-dependent inhibition of CFTR chloride channels by a novel peptide toxin. J. Biol. Chem. 282:37545-37555.
(2) 23) Fuller, M.D., Z.-R. Zhang, G. Cui, and N.A. McCarty (2005) The block of CFTR by scorpion venom is state-dependent. Biophys. J. 89: 3960-3975.
(3) 22) Thompson, C.H., D.M. Fields, Olivetti, P.R., M.D. Fuller, Z.-R. Zhang, and N.A. McCarty (2005) Inhibition of ClC-2 Cl- channels by a peptide component of scorpion venom. J. Membr. Biol. 208: 65-76.
(4) 1) Thompson, C.H., P.R. Olivetti, M.D. Fuller, C.S. Freeman, D. McMaster, R.F. French, J. Pohl, J. Kubanek, and N.A. McCarty. Isolation of a peptide toxin inhibitor of ClC-2 voltage-gated chloride channels. (submitted)
Techniques used in this lab: Molecular biology (mutagenesis, sequencing, plasmid manipulation); recombinant protein production (biochemistry, HPLC); electrophysiology (patch-clamp)
Additional Comments: News release on this project: http://gtresearchnews.gatech.edu/reshor/rh-ws08/venom.pdf
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