Associate Professor of Biological Sciences
PhD, 1999 Mayo Clinic College of Medicine
Molecular and cellular control of nerve development and disease
Research descriptionSpecification of axonal diameter is a key component of motor system development and functioning, as axonal diameter is major axonal property that specifies the velocity of electrical signal conduction in the nervous system.
The diameter of myelinated axonal segments (internodes) is increased relative to the diameter of unmyelinated axonal segments (Nodes of Ranvier). Compare the diameter of the left side of the axon in the EM to the diameter on the right side of the image. Formation of compact myelin and axonal accumulation of neurofilaments are both required for axonal diameter specification. However, it is unclear how axons and myelinating cells interact to determine axonal diameter. One proposed mechanism is that myelinating cells signal the axon resulting in alterations to the neurofilament network that support radial growth of the axon.
We are, also interested in the pathogenesis of neurodegenerative diseases such as Charcot-Marie-Tooth (CMT), amyotrophic lateral sclerosis (Lou Gehrig's Disease) and spinal muscular atrophy.
We generate genetically modified mice to investigate the role of the neurofilament network in establishing axonal diameter and to determine the mechanisms of disease pathogenesis in CMT2E.
Toedebusch, C.M., Snyder, J.C., Jones, M.R., Garcia, V.B., Johnson, G.C., Villalón, E.L., Coates, J.R., Garcia, M.L. Arginase-1 expressing microglia in close proximity to motor neurons were increased early in disease progression in canine degenerative myelopathy, a model of amyotrophic lateral sclerosis (2018) Molecular and Cellular Neuroscience, 88, pp. 148-157. DOI: 10.1016/j.mcn.2018.01.009
Villalón, E., Barry, D.M., Byers, N., Frizzi, K., Jones, M.R., Landayan, D.S., Dale, J.M., Downer, N.L., Calcutt, N.A., Garcia, M.L. Internode length is reduced during myelination and remyelination by neurofilament medium phosphorylation in motor axons (2018) Experimental Neurology, 306, pp. 158-168. DOI: 10.1016/j.expneurol.2018.05.009
Koeppen, J., Nguyen, A.Q., Nikolakopoulou, A.M., Garcia, M., Hanna, S., Woodruff, S., Figueroa, Z., Obenaus, A., Ethell, I.M. Functional consequences of synapse remodeling following astrocyte-specific regulation of ephrin-B1 in the adult hippocampus (2018) Journal of Neuroscience, 38 (25), pp. 5710-5726. DOI: 10.1523/JNEUROSCI.3618-17.2018
Villalón, E., Jones, M.R., Sibigtroth, C., Zino, S.J., Dale, J.M., Landayan, D.S., Shen, H., Cornelison, D.D.W., Garcia, M.L. Muscle spindle alterations precede onset of sensorimotor deficits in Charcot–Marie–Tooth type 2E (2017) Genes, Brain and Behavior, 16 (2), pp. 260-270.
Jones, M.R., Villalón, E., Northcutt, A.J., Calcutt, N.A., Garcia, M.L.Differential effects of myostatin deficiency on motor and sensory axons (2017) Muscle and Nerve, . Article in Press.
Toedebusch, C.M., Bachrach, M.D., Garcia, V.B., Johnson, G.C., Katz, M.L., Shaw, G., Coates, J.R., Garcia, M.L. Cerebrospinal Fluid Levels of Phosphorylated Neurofilament Heavy as a Diagnostic Marker of Canine Degenerative Myelopathy (2017) Journal of Veterinary Internal Medicine, 31 (2), pp. 513-520.
Nikolakopoulou, A.M., Koeppen, J., Garcia, M., Leish, J., Obenaus, A., Ethell, I.M. Astrocytic ephrin-BI regulates synapse remodeling following traumatic brain injury (2016) ASN Neuro, 8 (1), pp. 1-18.
Jones, M.R., Villalón, E., Garcia, M.L. Genetic Manipulation of Neurofilament Protein Phosphorylation (2016) Methods in Enzymology, 568, pp. 461-476.
Van Gronigen Caesar, G., Dale, J.M., Osman, E.Y., Garcia, M.L., Lorson, C.L., Schulz, L.C. Placental development in a mouse model of spinal muscular atrophy (2016) Biochemical and Biophysical Research Communications, 470 (1), pp. 82-87.
Shababi, M., Feng, Z., Villalon, E., Sibigtroth, C.M., Osman, E.Y., Miller, M.R., Williams-Simon, P.A., Lombardi, A., Sass, T.H., Atkinson, A.K., Garcia, M.L., Ko, C.-P., Lorson, C.L. Rescue of a mouse model of spinal muscular atrophy with respiratory distress type 1 by AAV9-IGHMBP2 is dose dependent (2016) Molecular Therapy, 24 (5), pp. 855-866.
Hodgkinson, V.L., Dale, J.M., Garcia, M.L., Weisman, G.A., Lee, J., Gitlin, J.D., Petris, M.J., 2015. X-linked spinal muscular atrophy in mice caused by autonomous loss of ATP7A in the motor neuron. Journal of Pathology, 236:241-250.
Villalón, E., Dale, J.M., Jones, M., Shen, H., and Garcia, M.L. (2015) Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve injury. Brain Research, 1627: 143-153.
Wortman, J.C., Shrestha, U.M., Barry, D.M., Garcia, M.L., Gross, S.P., Yu, C.C. (2014) Axonal transport: How high microtubule density can compensate for boundary effects. Biophysical Journal, 106: 813-823. PMCID: PMC3944719
Garcia, V.B., Garcia, M.L., Schulz, D.J., 2014. Quantitative expression profiling in mouse spinal cord reveals changing relationships among channel and receptor mRNA levels across postnatal maturation. Neuroscience, 277:21-333.
Cobb MS, Rose FF, Rindt H, Glascock JJ, Shababi M, Miller MR, Osman EY, Yen PF, Garcia ML, Martin BR, Wetz MJ, Mazzasette C, Feng Z, Ko CP, Lorson CL. (2013) Development and characterization of an SMN2-based intermediate mouse model of Spinal Muscular Atrophy. Human Molecular Genetics, 22: 1843-1855
Barry, D.M., Stevenson, W., Bober, B.G., Wiese, P.J., Dale, J.M., Barry, G.S., Byers, N.S., Strope, J.D., Chang, R., Schulz, D.J., Shah, S., Calcutt, N.A., Gebremichael, Y., Garcia, M.L. (2012) Expansion of NF-M c terminus increases axonal diameter independent of increases in conduction velocity or myelin thickness. The Journal of Neuroscience, 32: 6209-6219.
Dale, J.M. and Garcia, M.L. (2012) Neurofilament phosphorylation in development and disease: Which came first the phosphorylation or the accumulation? Journal of Amino Acids. Article ID 382107
Dale, J.M., Villalón, E., Shannon, S.S., Barry, D.M., Markey, R.M., Garcia, V.B., Garcia, M.L. (2012) Expressing hNF-LE397K results in abnormal gaiting in a transgenic model of CMT2E. Genes, Brain and Behavior, 11: 360-365. PMCID: PMC3319473
Rindt, H., Buckley, D.M., Vale, S.M., Krogman, M., Rose, F.F., Garcia, M.L., Lorson, C.L. (2012) Transgenic inactivation of murine myostatin does not decrease the severity of disease in a model of Spinal Muscular Atrophy. Neuromuscular Disorders, 22: 277-285. PMID: 22079083
Shen, H., Barry, D.M., Dale, J.M., Garcia, V.B., Calcutt, N.A., Garcia, M.L. (2011) Muscle pathology without severe nerve pathology in a new mouse model of Charcot-Marie-Tooth disease type 2E. Human Molecular Genetics, 20: 2535-2548. PMID: 21493625
Dale, J.M., Shen, H., Barry, D.M., Garcia, V.B., Rose, F.F., Lorson, C.L., Garcia, M.L. (2011) Altered axonal transport independent of global neurofilament alterations in SMAD7 mice. Acta Neuropathologica, 122: 331-341. PMID: 21681521
Shen, H.*, Barry, D.M.*, Garcia, M.L. (2010) Distal to proximal development of peripheral nerves requires the expression of neurofilament heavy. Neuroscience, 170: 16-21. PMCID: PMC2906171 *, Authors Contributed Equally.
Barry, D.M., Carpenter, C., Yager, C., Golik, B., Barry, K.J., Shen, H., Mikse, O., Eggert, L.S., Schulz, D.J., Garcia, M.L. (2010) Variation of the Neurofilament Medium KSP RepeatSub-domain across Mammalian Species: Implications for Altering Axonal Structure. Journal of ExperimentalBiology, 213: 128-136. PMID: 20008369
June 20, 2018
New study from Garcia lab shows a protein modification partially restores nerve insulation in mice
June 21, 2016
Two biology PhD students win best poster awards at national conferences
June 20, 2014
Oct. 31, 2013
MU receives $1.1 million training grant to increase diversity in biomedical sciences
April 17, 2012
New Genetically Engineered Mice Aid Understanding of Incurable Neuromuscular Disease
Jan. 31, 2012
System Failure: When Neural Pathways Go Silent, Heartbreak Follows
Sept. 26, 2011
Study provides new insight into fatal spinal disease