Manzoor A. Bhat, M.S., Ph.D.

Vice Dean for Research

Long School of Medicine

Professor, Cellular and Integrative Physiology

Currently seeking M.S. & Ph.D. students

Intricate molecular interactions between neurons and glial cells form the underlying basis of axonal insulation across species. Mutations in human genes that affect insulation of axons are associated with profound disturbances in normal impulse conduction and significant neurological disabilities. We are investigating the genetic and molecular basis of complex and reciprocal interactions between various types of glial cells, which play a key role in axonal insulation, blood-brain barrier formation and axon guidance across species. In vertebrates axonal insulation is achieved by myelination carried out by glial cells (Schwann cells and oligodendrocytes). The myelinated nerve fibers are organized into distinct domains that are necessary for rapid saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where myelin loops closely appose and form axo-glial septate junctions. We identified the vertebrate homologs of the Drosophila septate junction proteins and demonstrated a conserved role for these proteins in the organization and function of the axo-glial septate junctions in myelinated axons.

We generated Caspr, and Neurofascin (homologs of Drosophila nrx IV and nrg, respectively) mutant mice and demonstrated that in these mutants, paranodal axo-glial septate junctions fail to form and the axonal domain organization is disrupted. These defects result in severe motor deficits, decrease in nerve conduction velocity and axonal degeneration, thus demonstrating a critical role for these proteins in axon-glial interactions in myelinated axons. Our recent studies in mice, using neuron- and myelinating glia-specific inducible-Cre lines, show that axo-glial junction disruption in adults results in slow but progressive neurological disabilities leading to paralysis. These adult mouse mutants serve as models for human myelin-related pathologies.

For more details about our lab, please visit www.bhatlab.org

Research & Grants

Related Diseases: Multiple Sclerosis, Peripheral Neuropathy, Neurodevelopmental Disorders

Techniques Used: Genetics, Cell Biology, Biochemistry

Research Area/Field of Study: Physiology, Neuroscience

Research Profile

Bhat Lab
Publications

Sell LB, Shi Q, Bhat MA. (2024). Protocol for isolating and processing mouse sciatic nerve fibers for confocal immunohistochemistry. STAR Protocols. Volume 5, Issue 1, 15 March 2024, 102852

Chang C, Sell LB, Shi Q, Bhat MA. (2023). Mouse models of human CNTNAP1-associated congenital hypomyelinating neuropathy and genetic restoration of murine neurological deficits. Cell Rep. 2023 Oct 31;42(10):113274.

Qian Shi, Cheng Chang, Afaf Saliba and Manzoor A. Bhat (2022). Microglial mTOR Activation Upregulates Trem2 and Enhances β-Amyloid Plaque Clearance in the 5XFAD Alzheimer’s Disease Model. Journal of Neuroscience 7 June 2022, JN-RM-2427-21; DOI: https://doi.org/10.1523/JNEUROSCI.2427-21.2022

Chen S, Venkatesan A, Lin YQ, Xie J, Neely G, Banerjee S, Bhat MA. (2022). Drosophila Homolog of the Human Carpenter Syndrome Linked Gene, MEGF8, Is Required for Synapse Development and Function. J Neurosci. 2022 Sep 14;42(37):7016-7030.

Hiramoto T, Sumiyoshi A, Yamauchi T, Tanigaki K, Shi Q, Kang G, Ryoke R, Nonaka H, Enomoto S, Izumi T, Bhat MA, Kawashima R, Hiroi N. (2021). Tbx1, a gene encoded in 22q11.2 copy number variant, is a link between alterations in fimbria myelination and cognitive speed in mice. Mol Psychiatry. 2021 Nov 5. doi: 10.1038/s41380-021-01318-4.

Ye L, Orynbayev M, Zhu X, Lim EY, Dereddi RR, Agarwal A, Bergles DE, Bhat MA, Paukert M. (2020).. Ethanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release. Nat Commun. 2020 Dec 2;11(1):6157. doi: 10.1038/s41467-020-19475-5.

Kunisawa K, Hatanaka N, Shimizu T, Kobayashi K, Osanai Y, Mouri A, Shi Q, Bhat MA, Nambu A, Ikenaka K. (2020). Focal loss of the paranodal domain protein Neurofascin155 in the internal capsule impairs cortically induced muscle activity in vivo. Mol Brain. 2020 Nov 23;13(1):159. doi: 10.1186/s13041-020-00698-y.

Shi Q, Lee DY, Féliers D, Abboud HE, Bhat MA, Gorin Y (2020). Interplay between RNA-Binding Protein HuR and Nox4 As a Novel Therapeutic Target in Diabetic Kidney Disease. Mol Metab. 2020 Jun;36:100968. doi: 10.1016/j.molmet.2020.02.011.

Saifetiarova, J., and M. A. Bhat. (2019). Ablation of Cytoskeletal Scaffolding Proteins, Band 4.1B and Whirlin, Leads to Cerebellar Purkinje Axon Pathology and Motor Dysfunction. J Neurosci Res. 2019 Mar;97(3):313-331. doi: 10.1002/jnr.24352.

Shi Q, Saifetiarova J, Taylor AM, Bhat MA (2018) mTORC1 Activation by Loss of Tsc1 in Myelinating Glia Causes Downregulation of Quaking and Neurofascin 155 Leading to Paranodal Domain Disorganization. Front. Cell. Neurosci. doi: 10.3389/fncel.2018.00201

Kunisawa K, Shimizu T, Kushima I, Aleksic B, Mori D, Osanai Y, Kobayashi K, Taylor AM, Bhat MA, Hayashi A, Baba H, Ozaki N, Ikenaka K. (2018). Dysregulation of schizophrenia-related aquaporin 3 through disruption of paranode influences neuronal viability. J Neurochem. 2018 Jul 19. doi: 10.1111/jnc.14553.

Saifetiarova J, Shi Q, Paukert M, Komada M, Bhat MA (2018) Reorganization of Destabilized Nodes of Ranvier in βIV Spectrin Mutants Uncovers Critical Timelines for Nodal Restoration and Prevention of Motor Paresis. J. Neurosci. DOI: https://doi.org/10.1523/JNEUROSCI.0515-18.2018

Taylor AM, Shi Q, Bhat MA (2018) Simultaneous Ablation of Neuronal Neurofascin and Ankyrin G in Young and Adult Mice Reveals Age-Dependent Increase in Nodal Stability in Myelinated Axons and Differential Effects on the Lifespan. eNeuro DOI: https://doi.org/10.1523/ENEURO.0138-18.2018

Q. Shi, S. Viswanadhapalli, W. E. Friedrichs, C. Velagapudi, C. Szyndralewiez, S. Bansal, M.A. Bhat, G.G. Choudhury, and H. E. Abboud. (2018). Nox4 is a Target for Tuberin Deficiency Syndrome. Sci. Rep. 8, 3781.

Barron T, Saifetiarova J, Bhat MA, Kim JH. (2018). Myelination of Purkinje axons is critical for resilient synaptic transmission in the deep cerebellar nucleus. Sci Rep. 8(1):1022.

Saifetiarova, J., Liu, X., Taylor, A.M., Li, J. and Bhat, M.A. (2017). Axonal Domain Disorganization in Caspr1 and Caspr2 Mutant Myelinated Axons Affects Neuromuscular Junction Integrity Leading to Muscle Atrophy. J. Neurosci. Res. DOI: 10.1002/jnr.24052

Saifetiarova, J., Taylor, A.M., and Bhat, M.A. (2017) Early and Late Loss of the Cytoskeletal Scaffolding Protein, Ankyrin G Reveals its Role in Maturation and Maintenance of Nodes of Ranvier in Myelinated Axons. J Neurosci. 2661-16.2017

Taylor, A.M., Saifetyarova, J., and Bhat, M.A. (2017) Postnatal Loss of Neurofascin 186 and Neurofascin 155 Differentially Affects the Maintenance of Nodes of Ranvier and Health of Myelinated Axons. Front. Cell. Neurosci. 11:11. doi: 10.3389/fncel.2017.00011

Banerjee, S., Mino, R., Fisher, E. and Bhat, M.A. (2017). A Versatile Genetic Tool to Study Midline Glia Function in the Drosophila CNS. Developmental Biology 429(1):35-43.

Banerjee, S., Venkatesan, A. and Bhat, M.A. (2016) Neurexin, Neuroligin and Wishful Thinking Coordinate Synaptic Cytoarchitecture and Growth at Neuromuscular Junctions. Mol. Cell. Neurosci. 78, 9-24. (Featured on the Cover).

Mino, R.E., Rogers, S.L., Risinger, A.L., Rohena, C., Banerjee, S. and Bhat, M.A. (2016). Drosophila Ringmaker Regulates Microtubule Stabilization and Axonal Extension During Embryonic Development. J. Cell Sci. 129, 3282-3294.