Lee J. Martin, Ph.D.

Headshot of Lee J. Martin
  • Director, Graduate Training Program in Pathobiology
  • Professor of Pathology

Research Interests

Cell death signaling in neurological disease

Background

Dr. Lee J. Martin is a professor of Pathology in the Division of Neuropathology at the Johns Hopkins University School of Medicine. He has a secondary appointment as professor of Neuroscience. His research focuses on cell death signaling in acute and chronic neurological disease and the identification of molecular targets and therapeutics. DNA damage induced neural cell death and mitochondrial pathobiology are a major focus.

Dr. Martin is co-investigator in the Alzheimer’s Disease Research Center and is a member of the Graduate Program in Pathobiology at the Johns Hopkins School of Medicine. He is the Director of the Graduate Training Program in Pathobiology. He also teaches first-year medical students.

His research team is currently engaged in the use of animal and cell models of human neurodegenerative disease, including human induced pluripotent stem cells and CRISPR/Cas9 genome editing, to unravel the mechanisms of neurodegeneration and neuronal cell death. His fields of interest and expertise are ALS, Parkinson's disease, Alzheimer's disease, spinal muscular atrophy, and neonatal hypoxic-ischemic brain damage.

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Titles

  • Director, Graduate Training Program in Pathobiology
  • Co-Investigator, Neuropathology Core
  • Professor of Pathology
  • Professor of Anesthesiology and Critical Care Medicine

Departments / Divisions

Centers & Institutes

Education

Degrees

  • Ph.D.; University of Pennsylvania (Pennsylvania) (1986)

Research & Publications

Research Summary

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.

Selected Publications

View all on PubMed

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

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