Manoj Patel

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Primary Appointment

Professor of Anesthesiology, Anesthesiology

Education

  • BS, Applied Biology, University of Coventry
  • PhD, Physiology, University of Coventry
  • Postdoc, Electrophysiology, University of Virginia
  • Postdoc, Electrophysiology, University of Cambridge, Cambridge, England

Research Disciplines

Biophysics, Molecular Pharmacology, Neuroscience, Translational Science

Research Interests

Understanding the cellular mechanisms by which seizures are initiated in SCN8A epileptic encephalopathy (DEE13) and temporal lobe epilepsy. My lab uses a number of experimental techniques including patch clamp electrophysiology and in vivo seizure monitor

Research Description

The Patel lab focuses on understanding the cellular mechanisms by which seizures are initiated in SCN8A epileptic encephalopathy (DEE13). SCN8A EE is a severe genetic epilepsy syndrome caused by de novo mutations in the SCN8A gene, which codes for the voltage-gated sodium channel isoform Nav1.6. Our lab has two mouse models of patient-derived SCN8A mutations; N1768D (Scn8aD/+) which allows global heterozygous expression of the N1768D pathogenic Scn8a variant and a conditional mouse in which the expression of R1872W (Scn8aw/+) mutation is dependent on Cre recombinase. Using a variety of techniques including both in vivo and in vitro recordings to better understand the development and mechanisms of seizure initiation and seizure induced death (SUDEP) in these mice.

Personal Statement

The Patel lab focuses on understanding the cellular mechanisms by which seizures are initiated in SCN8A epileptic encephalopathy (DEE13). SCN8A EE is a severe genetic epilepsy syndrome caused by de novo mutations in the SCN8A gene, which codes for the voltage-gated sodium channel isoform Nav1.6. Our lab has two mouse models of patient-derived SCN8A mutations; N1768D (Scn8aD/+) which allows global heterozygous expression of the N1768D pathogenic Scn8a variant and a conditional mouse in which the expression of R1872W (Scn8aw/+) mutation is dependent on Cre recombinase. Using a variety of techniques including both in vivo and in vitro recordings to better understand the development and mechanisms of seizure initiation and seizure induced death (SUDEP) in these mice.

Training

  • Predoctoral Training in Neuroscience

Selected Publications

2024

Miralles, R., & Patel, M. K. (2024). Unspooling the Thread: VIP Interneurons Linked With Autism Spectrum Disorder Behaviors but Not Seizures in Dravet Syndrome. EPILEPSY CURRENTS, 24(1), 62-64. doi:10.1177/15357597231218876

2023

Wenker, I. C., & Patel, M. K. (2023). A Water Nymph's Curse and the Serotonergic Mechanism of Postictal Breathing Dysfunction. EPILEPSY CURRENTS, 23(6), 369-371. doi:10.1177/15357597231199340

Wenker, I. C., & Patel, M. K. (2023). Waiting to Inhale: Preventing Fatality From Seizure-Induced Apnea. EPILEPSY CURRENTS, 23(3), 185-187. doi:10.1177/15357597231159466

2022

Wenker, I. C., Wagley, P. K., Boscia, A. R., Lewis, C., & Patel, M. K. (2022). Opto- and Chemogenetic Dissection of Ictal Apnea Neural Circuitry.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36 Suppl 1. doi:10.1096/fasebj.2022.36.s1.r2354

Miralles, R., & Patel, M. K. (2022). That's a Wrap: Could Controlling Activity-Regulated Myelination Prevent Absence Seizures?. EPILEPSY CURRENTS, 22(6), 395-397. doi:10.1177/15357597221123898

Wenker, I. C., Boscia, A. R., Lewis, C., Tariq, A., Miralles, R., Hanflink, J. C., . . . Patel, M. K. (2022). Forebrain epileptiform activity is not required for seizure-induced apnea in a mouse model of Scn8a epilepsy. FRONTIERS IN NEURAL CIRCUITS, 16. doi:10.3389/fncir.2022.1002013

Wenker, I. C., Blizzard, E. A., Wagley, P. K., & Patel, M. K. (2022). Peri-Ictal Autonomic Control of Cardiac Function and Seizure-Induced Death. FRONTIERS IN NEUROSCIENCE, 15. doi:10.3389/fnins.2021.795145

Miralles, R. M., & Patel, M. K. (2022). It Takes Two to Tango: Channel Interplay Leads to Paradoxical Hyperexcitability in a Loss-of-Function Epilepsy Variant. EPILEPSY CURRENTS, 22(1), 69-71. doi:10.1177/15357597211057966

Wengert, E. R., Wagley, P. K., Strohm, S. M., Reza, N., Wenker, I. C., Gaykema, R. P., . . . Patel, M. K. (2022). Targeted Augmentation of Nuclear Gene Output (TANGO) of Scn1a rescues parvalbumin interneuron excitability and reduces seizures in a mouse model of Dravet Syndrome. BRAIN RESEARCH, 1775. doi:10.1016/j.brainres.2021.147743

Thompson, J. A., Miralles, R. M., Wengert, E. R., Wagley, P. K., Yu, W., Wenker, I. C., & Patel, M. K. (2022). Astrocyte reactivity in a mouse model of SCN8A epileptic encephalopathy. EPILEPSIA OPEN, 7(2), 280-292. doi:10.1002/epi4.12564

2021

Wengert, E. R., Miralles, R. M., Wedgwood, K. C. A., Wagley, P. K., Strohm, S. M., Panchal, P. S., . . . Patel, M. K. (2021). Somatostatin-Positive Interneurons Contribute to Seizures in SCN8A Epileptic Encephalopathy. JOURNAL OF NEUROSCIENCE, 41(44), 9257-9273. doi:10.1523/JNEUROSCI.0718-21.2021

Wengert, E. R., & Patel, M. K. (2021). One Size Doesn't Fit All: Variant-Specific Effects in SCN8A Encephalopathy. EPILEPSY CURRENTS, 21(3), 183-185. doi:10.1177/15357597211002206

Wengert, E. R., Wenker, I. C., Wagner, E. L., Wagley, P. K., Gaykema, R. P., Shin, J. -B., & Patel, M. K. (2021). Adrenergic Mechanisms of Audiogenic Seizure-Induced Death in a Mouse Model of SCN8A Encephalopathy. FRONTIERS IN NEUROSCIENCE, 15. doi:10.3389/fnins.2021.581048

Wenker, I. C., Teran, F. A., Wengert, E. R., Wagley, P. K., Panchal, P. S., Blizzard, E. A., . . . Patel, M. K. (2021). Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy. ANNALS OF NEUROLOGY, 89(5), 1023-1035. doi:10.1002/ana.26053

Wengert, E. R., & Patel, M. K. (2021). The Role of the Persistent Sodium Current in Epilepsy. EPILEPSY CURRENTS, 21(1), 40-47. doi:10.1177/1535759720973978

2020

Wheeler, M. A., Deppmann, C. D., Patel, M. K., & Guler, A. D. (2020). Reply to: Magneto is ineffective in controlling electrical properties of cerebellar Purkinje cells, Assessing the utility of Magneto to control neuronal excitability in the somatosensory cortex and Revaluation of magnetic properties of Magneto. NATURE NEUROSCIENCE, 23(9), 1051-+. doi:10.1038/s41593-019-0472-6

2019

Wengert, E. R., Tronhjem, C. E., Wagnon, J. L., Johannesen, K. M., Petit, H., Krey, I., . . . Moller, R. S. (2019). Biallelic inherited SCN8A variants, a rare cause of SCN8A-related developmental and epileptic encephalopathy. EPILEPSIA, 60(11), 2277-2285. doi:10.1111/epi.16371

Wengert, E. R., Saga, A. U., Panchal, P. S., Barker, B. S., & Patel, M. K. (2019). Prax330 reduces persistent and resurgent sodium channel currents and neuronal hyperexcitability of subiculum neurons in a mouse model of SCN8A epileptic encephalopathy. NEUROPHARMACOLOGY, 158. doi:10.1016/j.neuropharm.2019.107699

Nigam, A., Hargus, N. J., Barker, B. S., Ottolini, M., Hounshell, J. A., Bertram, E. H. I. I. I., . . . Patel, M. K. (2019). Inhibition of T-Type calcium channels in mEC layer II stellate neurons reduces neuronal hyperexcitability associated with epilepsy. EPILEPSY RESEARCH, 154, 132-138. doi:10.1016/j.eplepsyres.2019.05.006

Bunton-Stasyshyn, R. K. A., Wagnon, J. L., Wengert, E. R., Barker, B. S., Faulkner, A., Wagley, P. K., . . . Meisler, M. H. (2019). Prominent role of forebrain excitatory neurons in SCN8A encephalopathy. BRAIN, 142, 362-375. doi:10.1093/brain/awy324

2018

Cottrell, G. S., Soubrane, C. H., Hounshell, J. A., Lin, H., Owenson, V., Rigby, M., . . . Stephens, G. J. (2018). CACHD1 is an α2δ-Like Protein That Modulates CaV3 Voltage-Gated Calcium Channel Activity. JOURNAL OF NEUROSCIENCE, 38(43), 9186-9201. doi:10.1523/JNEUROSCI.3572-15.2018

Baker, E. M., Thompson, C. H., Hawkins, N. A., Wagnon, J. L., Wengert, E. R., Patel, M. K., . . . Kearney, J. A. (2018). The novel sodium channel modulator GS-458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy. EPILEPSIA, 59(6), 1166-1176. doi:10.1111/epi.14196

Wagnon, J. L., Mencacci, N. E., Barker, B. S., Wengert, E. R., Bhatia, K. P., Balint, B., . . . Meisler, M. H. (2018). Partial loss-of-function of sodium channel SCN8A in familial isolated myoclonus. HUMAN MUTATION, 39(7), 965-969. doi:10.1002/humu.23547

Good, M. E., Eucker, S. A., Li, J., Bacon, H. M., Lang, S. M., Butcher, J. T., . . . Isakson, B. E. (2018). Endothelial cell Pannexin1 modulates severity of ischemic stroke by regulating cerebral inflammation and myogenic tone. JCI INSIGHT, 3(6). doi:10.1172/jci.insight.96272

2017

Barker, B. S., Nigam, A., Ottolini, M., Gaykema, R. P., Hargus, N. J., & Patel, M. K. (2017). Pro-excitatory alterations in sodium channel activity facilitate subiculum neuron hyperexcitability in temporal lobe epilepsy. NEUROBIOLOGY OF DISEASE, 108, 183-194. doi:10.1016/j.nbd.2017.08.018

Ottolini, M., Barker, B. S., Gaykema, R. P., Meisler, M. H., & Patel, M. K. (2017). Aberrant Sodium Channel Currents and Hyperexcitability of Medial Entorhinal Cortex Neurons in a Mouse Model of SCN8A Encephalopathy. JOURNAL OF NEUROSCIENCE, 37(32), 7643-7655. doi:10.1523/JNEUROSCI.2709-16.2017

Wagnon, J. L., Barker, B. S., Ottolini, M., Park, Y., Volkheimer, A., Valdez, P., . . . Meisler, M. H. (2017). Loss-of-function variants of SCN8A in intellectual disability without seizures. NEUROLOGY-GENETICS, 3(4). doi:10.1212/NXG.0000000000000170

Gaykema, R. P., Newmyer, B. A., Ottolini, M., Raje, V., Warthen, D. M., Lambeth, P. S., . . . Scott, M. M. (2017). Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight. JOURNAL OF CLINICAL INVESTIGATION, 127(3), 1031-1045. doi:10.1172/JCI81335

2016

Wheeler, M. A., Smith, C. J., Ottolini, M., Barker, B. S., Purohit, A. M., Grippo, R. M., . . . Guler, A. D. (2016). Genetically targeted magnetic control of the nervous system. NATURE NEUROSCIENCE, 19(5), 756-+. doi:10.1038/nn.4265

Rivara, M., Patel, M. K., Rapalli, A., & Zuliani, V. (2016). Sodium Channel Blocking Activity and In-vivo Testing of New Phenyl-imidazole Derivatives. LETTERS IN DRUG DESIGN & DISCOVERY, 13(9), 962-967. doi:10.2174/1570180813666160714125755

Barker, B. S., Ottolini, M., Wagnon, J. L., Hollander, R. M., Meisler, M. H., & Patel, M. K. (2016). The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin. EPILEPSIA, 57(9), 1458-1466. doi:10.1111/epi.13461

Meisler, M. H., Helman, G., Hammer, M. F., Fureman, B. E., Gaillard, W. D., Goldin, A. L., . . . Scheffer, I. E. (2016). SCN8A encephalopathy: Research progress and prospects. EPILEPSIA, 57(7), 1027-1035. doi:10.1111/epi.13422

Alexandrou, A. J., Brown, A. R., Chapman, M. L., Estacion, M., Turner, J., Mis, M. A., . . . Stevens, E. B. (2016). Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release. PLOS ONE, 11(4). doi:10.1371/journal.pone.0152405

Warthen, D. M., Lambeth, P. S., Ottolini, M., Shi, Y., Barker, B. S., Gaykema, R. P., . . . Scott, M. M. (2016). Activation of Pyramidal Neurons in Mouse Medial Prefrontal Cortex Enhances Food-Seeking Behavior While Reducing Impulsivity in the Absence of an Effect on Food Intake. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 10. doi:10.3389/fnbeh.2016.00063

Wagnon, J. L., Barker, B. S., Hounshell, J. A., Haaxma, C. A., Shealy, A., Moss, T., . . . Meisler, M. H. (2016). Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy. ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 3(2), 114-123. doi:10.1002/acn3.276

2014

Zuliani, V., Rapalli, A., Patel, M. K., & Rivara, M. (2015). Sodium channel blockers: a patent review (2010-2014). EXPERT OPINION ON THERAPEUTIC PATENTS, 25(3), 279-290. doi:10.1517/13543776.2014.995628

2013

Rivara, M., Patel, M. K., Amori, L., & Zuliani, V. (2013). ChemInform Abstract: Inhibition of Nav1.6 Sodium Channel Currents by a Novel Series of 1,4âDisubstitutedâtriazole Derivatives Obtained via CopperâCatalyzed Click Chemistry.. ChemInform, 44(7). doi:10.1002/chin.201307114

Hargus, N. J., Nigam, A., Bertram, E. H. I. I. I., & Patel, M. K. (2013). Evidence for a role of Nav1.6 in facilitating increases in neuronal hyperexcitability during epileptogenesis. JOURNAL OF NEUROPHYSIOLOGY, 110(5), 1144-1157. doi:10.1152/jn.00383.2013

2012

Rivara, M., Patel, M. K., Amori, L., & Zuliani, V. (2012). Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4-disubstituted-triazole derivatives obtained via copper-catalyzed click chemistry. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 22(20), 6401-6404. doi:10.1016/j.bmcl.2012.08.067

Walls, T. H., Grindrod, S. C., Beraud, D., Zhang, L., Baheti, A. R., Dakshanamurthy, S., . . . MacArthur, L. H. (2012). Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent. BIOORGANIC & MEDICINAL CHEMISTRY, 20(17), 5269-5276. doi:10.1016/j.bmc.2012.06.042

Hargus, N. J., Jennings, C., Perez-Reyes, E., Bertram, E. H., & Patel, M. K. (2012). Enhanced actions of adenosine in medial entorhinal cortex layer II stellate neurons in temporal lobe epilepsy are mediated via A1-receptor activation. EPILEPSIA, 53(1), 168-176. doi:10.1111/j.1528-1167.2011.03337.x

2011

Davis, G. C., Kong, Y., Paige, M., Li, Z., Merrick, E. C., Hansen, T., . . . Brown, M. L. (2012). Asymmetric synthesis and evaluation of a hydroxyphenylamide voltage-gated sodium channel blocker in human prostate cancer xenografts. BIOORGANIC & MEDICINAL CHEMISTRY, 20(6), 2180-2188. doi:10.1016/j.bmc.2011.08.061

De Oliveira, E. O., Graf, K. M., Patel, M. K., Baheti, A., Kong, H. -S., MacArthur, L. H., . . . Paige, M. (2011). Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers. BIOORGANIC & MEDICINAL CHEMISTRY, 19(14), 4322-4329. doi:10.1016/j.bmc.2011.05.043

2010

Hargus, N. J., Merrick, E. C., Nigam, A., Kalmar, C. L., Baheti, A. R., Bertram, E. H. I. I. I., & Patel, M. K. (2011). Temporal lobe epilepsy induces intrinsic alterations in Na channel gating in layer II medial entorhinal cortex neurons. NEUROBIOLOGY OF DISEASE, 41(2), 361-376. doi:10.1016/j.nbd.2010.10.004

Zuliani, V., Fantini, M., Nigam, A., Stables, J. P., Patel, M. K., & Rivara, M. (2010). Anticonvulsant activity of 2,4(1H)-diarylimidazoles in mice and rats acute seizure models. BIOORGANIC & MEDICINAL CHEMISTRY, 18(22), 7957-7965. doi:10.1016/j.bmc.2010.09.029