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Alicia Timme-Laragy

Associate Professor

Research Interests

I am a toxicologist with extensive training in developmental and molecular toxicology. A primary goal of my work has been to understand how the transcription factors aryl hydrocarbon receptor (Ahr) and Nfe2l2 (Nrf2) play a role in mediating the toxic and/or adaptive responses to xenobiotic exposures during embryonic development, with an emphasis on redox-active toxicants such as PCBs, PFAS, and chemicals found in personal care products. My research has served to build and firmly establish the zebrafish embryo model as a robust in vivo model in which to study chemical-induced redox stress. We now have a well-defined system in which to address questions of how contaminants that cause oxidative stress cause embryotoxicity, and what the implications are for human exposures at comparable life stages.

Aberrant disruption of signaling pathways during development can result in structural alterations predisposing individuals to diseases emerging at later life stages. We focus largely on pancreas development, testing the hypothesis that developmental toxicant exposures result in deviant development of the pancreas via a redox stress mechanism that contributes to later-life metabolic dysfunction.

Current Research

We have several active projects in the lab:

1) Understanding the relationship between Nrf2 and glutathione during embryonic development. This project probes the role of glutathione in differential susceptibility to Nrf2 activation during development following exposure to PFOS, MEHP, or PCB-126. We are examining the effects on pancreatic beta cells in the zebrafish, and also investigating this relationship using cell culture models.

2) Metabolic consequences of preconception exposure to perfluorinated compounds. In this project we are examining the effects of maternal exposures to PFCs and the impact on yolk loading into the oocyte and the effects on the metabolic health of the developing embryo.

3) Redox modulation of pancreas development. In this project we aim to understand how modulation of glutathione content and redox state alter development of the endocrine and exocrine pancreas, and what critical windows are important for chemical exposures.

4) Toxicity of emerging contaminants. We are interested in examining embryotoxicity of under-studied, emerging contaminants that may pose a risk to either wildlife or human health. We have projects examining butylparaben (a preservative in personal care products), PCB-11, and some disinfection by-products.

Academic Background

BA- Franklin & Marshall College, 2000
PhD- Nicholas School of the Environment, Duke University, 2007

Postdoctoral Training- Woods Hole Oceanographic Institution 2007-2013

Annunziato KM, Doherty J, Lee J, Clark JM, Liang W, Clark CW, Nguyen M, Roy MA, Timme-Laragy AR. (2020). Chemical Characterization of a Legacy AFFF (Aqueous Film-Forming Foam) Sample and Developmental Toxicity in Zebrafish (Danio rerio). Environmental Health Perspectives. doi 10.1289/EHP6470
Roy MA, Duche PR, Timme-Laragy AR. (2020). The sulfate metabolite of 3,3’-dichlorobiphenyl (PCB-11) impairs Cyp1a activity and increases hepatic neutral lipids in zebrafish larvae (Danio rerio). Chemosphere. 260:127609. doi: 10.1016/j.chemosphere.2020.127609. PMID: 32693259 Sant KE, Jacobs HM, Xu J, Borofski KA, Moss LG, Moss JB, Timme-Laragy AR. Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model. Toxics. 2016 Sep;4(3). pii: 20. doi: 10.3390/toxics4030020. PMID: 28393070
Sant KE, Moreau HM, Williams LM, Jacobs HM, Bowsher AM, Boisvert JD, Smolowitz RM, Pantazis J, Annunziato KM, Nguyen M, Timme-Laragy AR. (2020) Embryonic exposures to mono-2-ethylhexyl phthalate (MEHP) induce larval steatosis in zebrafish independent of Nrf2a signaling. Journal of Developmental Origins of Health and Disease. Feb 17:1-9. doi: 10.1017/S2040174420000057. PMC7429360
Rastogi AR, Clark C, Conlin S, Brown SE, Timme-Laragy AR. (2019) Mapping glutathione utilization in the developing zebrafish (Danio rerio) embryo. Redox Biology. Sep;26:101235. doi: 10.1016/j.redox.2019.101235. PMC6581987
Sant KE, Venezia O, Sinno PP, Moss JB, Timme-Laragy AR. (2019) Perfluorobutanesulfonic acid disrupts pancreatic organogenesis and regulation of lipid metabolism in the zebrafish, Danio rerio. Toxicological Sciences. 167(1):258-68. doi: 10.1093/toxsci/kfy237. PMC6317420
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
Contact Info

Environmental Health Sciences
Goessmann 171B
686 N Pleasant St
Amherst, MA 01003-9292

Office: 413-545-7423
Email: aliciat@umass.edu