B.A., Franklin and Marshall College, 2000; Ph.D., Duke University, 2007; Post-doctoral, Woods Hole Oceanographic Institution
Area(s) of Specialization:
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.
Sant KE, Jacobs HM, Borofski KA, Moss JB, Timme-Laragy AR. Embryonic exposures to perfluorooctanesulfonic acid (PFOS) disrupt pancreatic organogenesis in the zebrafish, Danio rerio. Environ Pollut. 2017 Jan;220(Pt B):807-817. doi: 10.1016/j.envpol.2016.10.057. PMID: 27810111
Sant KE, Jacobs HM, Xu J, Borofski KA, Moss LG, Moss JB, and Timme-Laragy AR. Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model. Toxics 2016, 4(3), 20; doi:10.3390/toxics4030020
Timme-Laragy AR, Sant KE, Rousseau ME, diIorio PJ. Deviant development of pancreatic beta cells from embryonic exposure to PCB-126 in zebrafish. Comp Biochem Physiol C Toxicol Pharmacol. 2015 Dec;178:25-32. doi: 10.1016/j.cbpc.2015.08.012. PMID: 26393762
Rousseau ME, Sant KE, Borden LR, Franks DG, Hahn ME, Timme-Laragy AR. Regulation of Ahr signaling by Nrf2 during development: Effects of Nrf2a deficiency on PCB126 embryotoxicity in zebrafish (Danio rerio). Aquat Toxicol. 2015 Oct;167:157-71. doi: 10.1016/j.aquatox.2015.08.002. PMID: 26325326
Timme-Laragy AR, Goldstone JV, Imhoff BR, Stegeman JJ, Hahn ME, Hansen JM. Glutathione redox dynamics and expression of glutathione-related genes in the developing embryo. Free Radic Biol Med. 2013 Dec;65:89-101. doi: 10.1016/j.freeradbiomed.2013.06.011. PMID: 23770340
Timme-Laragy AR, Karchner SI, Franks DG, Jenny MJ, Harbeitner RC, Goldstone JV, McArthur AG, Hahn ME. Nrf2b, novel zebrafish paralog of oxidant-responsive transcription factor NF-E2-related factor 2 (NRF2). J Biol Chem. 2012 Feb 10;287(7):4609-27. doi: 10.1074/jbc.M111.260125. PMID: 22174413