Alicia R. Timme-Laragy
B.A., Franklin and Marshall College, 2000; Ph.D., Duke University, 2007; Post-doctoral, Woods Hole Oceanographic Institution
Developmental toxicology, oxidative stress, Nrf and Ahr transcription factors, glutathione
Many environmental pollutants, such as PAHs, PCBs, metals, and pesticides, can alter cellular redox state and cause oxidative stress. Oxidative stress during embryonic development can cause birth defects, and may also be a contributor to the developmental origins of adult disease. However, very little is known about how embryos respond to oxidative stress, or what antioxidant defenses exist during early life stages. How and when do these defenses develop? How are they regulated? And how do these impact developmental toxicity? Could embryonic redox state at the time of chemical exposure be a key factor in determining later-life consequences of early life stage exposures?
Using the zebrafish as a model system, Dr. Timme-Laragy’s research aims to elucidate cellular and molecular mechanisms of toxicant-induced oxidative stress in embryonic development, and identify later-life consequences of embryonic exposure to oxidative stress. Of particular interest is to understand how transcription factors, such as Ahr and Nrf2, play a role in the ontogeny and adaptive response of antioxidant defenses during embryonic development.
Harbeitner RC, Hahn ME, Timme-Laragy AR. (2013). Differential sensitivity to pro-oxidant exposure in two populations of killifish Fundulus heteroclitus). Ecotoxicology. in press.
Timme-Laragy AR, Karchner SI, Franks DG, Jenny MJ, Harbeitner, RC, McArthur AG, Goldstone JV, Hahn ME. (2012) Nrf2b: novel zebrafish paralog of the oxidant-responsive transcription factor NF-E2-related factor 2 (NRF2). Journal of Biological Chemistry. 287(7):4609-27.
Jonsson ME Kubota A, Timme-Laragy AR, Woodin B, Stegeman JJ. (2012) Ahr2-dependence of PCB126 effects on the swimbladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish. Toxicology and Applied Pharmacology. 265(2):166-74.
Timme-Laragy AR, Van Tiem LA, Di Giulio RT. (2009). Antioxidant responses and NRF2 in synergistic developmental toxicity of PAHs in zebrafish. Toxicological Sciences. 109(2):217-27.
Timme-Laragy AR, Cockman CJ, Matson CW, Di Giulio RT. (2007). Synergistic induction of AHR regulated genes in developmental toxicity from co-exposure to two model PAHs in zebrafish. Aquatic Toxicology 85(4): 241-250.