Dr. Martin is studying mechanisms of neuronal death in adult and developing central nervous systems. He is testing the hypothesis that selective vulnerability (when only certain groups of neurons degenerate after an acute neurological insult) is dictated by brain regional connectivity, mitochondrial function and oxidative stress and is mediated by excitotoxic cell death resulting from abnormalities in excitatory, glutamatergic signal transduction pathways, including glutamate transporters and glutamate receptors as well as their downstream intracellular signaling molecules.
He is also investigating the contribution of neuronal/glial apoptosis and necrosis as cell death pathways in animal (including transgenic mice) models of acute and progressive neurodegeneration. Dr. Martin uses a variety of anatomical and molecular neurobiological approaches, including neuronal tract-tracing techniques, immunocytochemistry, immunoblotting, antipeptide antibody production, transmission electron microscopy, and DNA analysis to determine the precise regional and cellular vulnerabilities and the synaptic and molecular mechanisms that result in selective neuronal degeneration.
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Kim BW, Ryu J, Jeong YE, Kim J and Martin LJ. Human Motor Neurons With SOD1-G93A Mutation Generated From CRISPR/Cas9 Gene-Edited iPSCs Develop Pathological Features of Amyotrophic Lateral Sclerosis. Front Cell Neurosci. 2020 Nov 19;14:604171. doi: 10.3389/fncel.2020.604171. eCollection 2020. PMID: 33328898
Kim BW, Jeong YE, Wong M, Martin LJ.DNA damage accumulates and responses are engaged in human ALS brain and spinal motor neurons and DNA repair is activatable in iPSC-derived motor neurons with SOD1 mutations. Acta Neuropathol Commun. 2020 Jan 31;8(1):7. doi: 10.1186/s40478-019-0874-4. PMID: 32005289
Martin LJ, Chang Q. DNA Damage Response and Repair, DNA Methylation, and Cell Death in Human Neurons and Experimental Animal Neurons Are Different. J Neuropathol Exp Neurol. 2018 Jul 1;77(7):636-655. doi: 10.1093/jnen/nly040. PMID: 29788379
Martin LJ, Fancelli D, Wong M, Niedzwiecki M, Ballarini M, Plyte S, Chang Q. GNX-4728, a novel small molecule drug inhibitor of mitochondrial permeability transition, is therapeutic in a mouse model of amyotrophic lateral sclerosis. Front Cell Neurosci. 2014 Dec 19;8:433. doi: 10.3389/fncel.2014.00433. eCollection 2014. PMID: 25565966
Wong M, Gertz B, Chestnut BA, Martin LJ. Mitochondrial DNMT3A and DNA methylation in skeletal muscle and CNS of transgenic mouse models of ALS. Front Cell Neurosci. 2013 Dec 25;7:279. doi: 10.3389/fncel.2013.00279. eCollection 2013. PMID: 24399935