The Maragakis lab's main focus is in understanding disease mechanisms and targeting cell therapeutics for Amyotrophic Lateral Sclerosis (ALS). In collaboration with Johns Hopkins neuroscientists, his laboratory helped create stem cell lines from ALS patients using induced pluripotent stem cell (iPSC) methodologies. These cells will allow for the development of human cell lines which can be used for both the basic understanding of ALS astrocyte and motor neuron biology, as well as eventually identifying ALS therapeutics. Researchers in the Maragakis lab also focus on the potential therapeutic role of astrocyte replacement in ALS using glial stem cells. By transplanting glial stem cells into ALS animal models, the researchers in the Maragakis lab found that the stem cells can engraft, migrate and differentiate into astrocytes, and subsequently provide neuroprotection to vulnerable motor neuron pools. The team uses stem cell transplantation biology to understand the influences of mutant SOD1 astrocytes on normal, healthy motor neurons. A significant laboratory effort is underway to translate these discoveries into therapies for patients with ALS.
- Haidet-Phillips AM, Roybon L, Gross SK, Tuteja A, Donnelly CJ, Richard JP, Ko M, Sherman A, Eggan K, Henderson CE, Maragakis NJ. Gene profiling of human induced pluripotent stem cell-derived astrocyte progenitors following spinal cord engraftment. Stem Cells Transl Med. 2014 May;3(5):575-85. doi: 10.5966/sctm.2013-0153. Epub 2014 Mar 6. PMID: 24604284
- Haeusler AR, Donnelly CJ, Periz G, Simko EA, Shaw PG, Kim MS, Maragakis NJ, Troncoso JC, Pandey A, Sattler R, Rothstein JD, Wang J. C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature. 2014 Mar 13;507(7491):195-200. doi: 10.1038/nature13124. Epub 2014 Mar 5. PMID: 24598541
- Rutkove SB, Caress JB, Cartwright MS, Burns TM, Warder J, David WS, Goyal N, Maragakis NJ, Benatar M, Sharma KR, Narayanaswami P, Raynor EM, Watson ML, Shefner JM. Electrical impedance myography correlates with standard measures of ALS severity. Muscle Nerve. 2014 Mar;49(3):441-3. doi: 10.1002/mus.24128. Epub 2013 Dec 19. PMID: 24273034
- Haidet-Phillips AM, Gross SK, Williams T, Tuteja A, Sherman A, Ko M, Jeong YH, Wong PC, Maragakis NJ. Altered astrocytic expression of TDP-43 does not influence motor neuron survival. Exp Neurol. 2013 Dec;250:250-9. doi: 10.1016/j.expneurol.2013.10.004. Epub 2013 Oct 9. PMID: 24120466
- Roth NM, Saidha S, Zimmermann H, Brandt AU, Oberwahrenbrock T, Maragakis NJ, Tumani H, Ludolph AC, Meyer T, Calabresi PA, Paul F. Optical coherence tomography does not support optic nerve involvement in amyotrophic lateral sclerosis. Eur J Neurol. 2013 Aug;20(8):1170-6. doi: 10.1111/ene.12146. Epub 2013 Apr 14. PMID: 23582075