As a postdoctoral scholar at Dr. Megan Dennis lab I used zebrafish as a model to identify and characterize synaptic alterations in mutations that lead to epilepsy and or autism spectrum disorder.
PhD Research Focus My research as a graduate student was focused on understanding the mechanism of toxicity of an environmental neurotoxicant, methylmercury (MeHg), on spinal cord motor neurons.
Why? Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in humans. It is characterized by the degeneration of upper and lower motor neurons, leading to death approximately five years after being diagnosed. There are two forms of ALS: familial (FALS) which accounts for 10% of all ALS cases and sporadic (SALS) which comprises 90% of all ALS cases. In both FALS and SALS the clinical and pathological manifestations are the same1. Genetic and environmental factors are considered possible contributors to the development of both forms2,3. One environmental toxicant that has been considered a possible contributor to the development of ALS is methylmercury (MeHg)2-4. MeHg is a persistent environmental neurotoxicant to which humans are exposed mainly through the consumption of seafood. Motor neurons are one of the targets of MeHg toxicity and exposure to mercury compounds has been reported to lead to ALS-like syndromes2,4. In a study using the ALS mouse model SOD1-G93A, exposure to MeHg led to early onset of ALS-like phenotype, presenting a possible gene environment interaction5. One of the factors contributing to MeHg-induced motor neuron degeneration is alterations in intracellular calcium5. These effects have not been well characterized and are the focus of my dissertation project. The findings of my work will: 1) contribute to the understanding of MeHg-induced toxicity in motor neurons, 2) provide a platform for ongoing studies in our lab focused on identifying the underlying mechanisms by which MeHg is contributing to the accelerated onset of ALS-like phenotype in the SOD1-G93A mouse.
References: 1. Cleveland, D. W. & Rothstein, J. D. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci. 2, 806–19 (2001). 2. Johnson, F. O. & Atchison, W. D. The role of environmental mercury, lead and pesticide exposure in development of amyotrophic lateral sclerosis. Neurotoxicology 30, 761–5 (2009). 3. Trojsi, F., Monsurrò, M. R. & Tedeschi, G. Exposure to environmental toxicants and pathogenesis of amyotrophic lateral sclerosis: state of the art and research perspectives. Int. J. Mol. Sci. 14, 15286–311 (2013). 4. Praline, J. et al. ALS and mercury intoxication: a relationship? Clin. Neurol. Neurosurg. 109, 880–3 (2007). 5. Johnson, F. O. et al. Exposure to an environmental neurotoxicant hastens the onset of amyotrophic lateral sclerosis-like phenotype in human Cu2+/Zn2+ superoxide dismutase 1 G93A mice : J. Pharmacol. Exp. Ther. 338, 518–527 (2011).