Research Bio
Toxicant Exposure and Brain Development
Although the developing brain is particularly vulnerable to a wide variety of environmental chemicals, little is known about the mechanisms underlying adverse effects following exposure. Normal brain development is orchestrated by precisely timed cellular and molecular events including proliferation, migration, differentiation, synaptogenesis, and programmed cell death (apoptosis). All these processes are potential targets for perturbation by exposures to environmental contaminants during critical developmental periods.
Our laboratory is currently investigating the impact of perinatal exposure to environmental agents on neurogenesis and neuronal differentiation in the developing brain. Both in vivo and in vitro models are being used to identify cellular targets and molecular mechanisms for neurotoxicity. The laboratory uses morphological and biochemical techniques to define toxicant effects on cell proliferation, neuronal migration, neurite development, synaptogenesis and apoptosis. We are also interested in correlating morphologic changes following toxicant exposure with alterations in expression of genes and proteins related to cytoskeletal dynamics, cell cycle control, and neurotrophic factor signaling .
Current projects involve several agents: endocrine disruptors, such as polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); abused substances (toluene and nicotine); and metals (mercury). The long term goal of our research is to determine the relationship between disrupted neuronal production or maturation and functional deficits produced by toxicant exposure during critical periods of brain development.
2010 May
Latchney, S.E.; Lioy, D.T., Henry, E.C.; Gasiewicz, T.A.; Opanashuk, L.A. "Aryl Hydrocarbon Activation by 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure Interferes with Neural Precursor Cell Development." Stem Cells Dev.. 2010; . |
2010
Janelsins, M.C.; Roscoe, J.A.; Berg, M.J.; Thompson, B.D.; Gallagher, M.J.; Morrow. G.R.; Heckler, C.E.; Jean-Pierre, P.; Opanashuk, L.A.; Gross, R.A. "IGF-1 partially restores chemotherapy-induced reductions in neural cell proliferation in adult C57BL/6 mice." Cancer Invest.. 2010; 28(5): 544-53. |
2010
Fox D.A.; Opanashuk, L.; Zharkovsky, A,; Weiss B. "Gene-chemcial interactions in the developing mammalian nervous system: Effects on prolieration, neurogenesis and differentiation." Neurotoxicology. 2010; . |
2009 Feb
Singh, K.P.; Casado, F.L.; Opanashuk, L.; Gasiewicz, T.A. "The aryl hydrocarbon receptor has a normal function in the regulation of hematopoietic adn other tem/progenitor cell populations." Biochem Pharmacol. 2009; 77(4): 577-87. |
2008 May
Collins, L.L.; Williamson, M.A.; Thompson, B.D.; Dever, D.P.; Gasiewicz, T.A; Opanashuk, L. "2,3,7,8-tetracholorodibenzo-p-dioxin Exposure Disrupts Granule Neuron Prescursor Maturation in the Developing Mouse Cerebellum." Toxicol Sci. 2008; 103(1): 125-36. |
