Manoj Patel

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Primary Appointment

Associate Professor, 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

Wenker IC, Teran FA, Wengert ER, Wagley PK, Panchal PS, Blizzard EA, Saraf P, Wagnon JL, Goodkin HP, Meisler MH, Richerson GB, Patel MK, Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy., 2021; Annals of Neurology. 89(5) 1023-1035. PMID: | PMCID: PMC8411945

Wengert ER, Wenker IC, Wagner EL, Wagley PK, Gaykema RP, Shin J, Patel MK, Adrenergic Mechanisms of Audiogenic Seizure-Induced Death in a Mouse Model of SCN8A Encephalopathy., 2021; Front Neurosci. (15) 581048. PMID: | PMCID: PMC7982890

Wengert ER, Tronhjem CE, Wagnon JL, Johannesen KM, Petit H, Krey I, Saga AU, Panchal PS, Strohm SM, Lange J, Kamphausen SB, Rubboli G, Lemke JR, Gardella E, Patel MK, Meisler MH, Moller RS, Biallelic inherited SCN8A variants, a rare cause of SCN8A-related developmental and epileptic encephalopathy., 2019; Epilepsia. 60(11) 2277-2285. PMID: | PMCID: PMC6842408

Wengert ER, Saga AU, Panchal PS, Barker BS, Patel MK, Prax330 reduces persistent and resurgent sodium channel currents and neuronal hyperexcitability of subiculum neurons in a mouse model of SCN8A epileptic encephalopathy., 2019; Neuropharmacology. (158) 107699. PMID: | PMCID: PMC6745260

Ottolini M, Barker BS, Gaykema RP, Meisler MH, Patel MK, Aberrant Sodium Channel Currents and Hyperexcitability of Medial Entorhinal Cortex Neurons in a Mouse Model of SCN8A Encephalopathy., 2017; J Neurosci. 37(32) 7643-7655. PMID: | PMCID: PMC5551062

Barker BS, Ottolini M, Wagnon JL, Hollander RM, Meisler MH, Patel MK, The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin., 2016; Epilepsia. 57(9) 1458-66. PMID: | PMCID: PMC5012949

Wagnon JL, Barker BS, Hounshell JA, Haaxma CA, Shealy A, Moss T, Parikh S, Messer RD, Patel MK, Meisler MH, Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy., 2015; Annals of Clinical and Translational Neurology. 3(2) 114-23. PMID: | PMCID: PMC4748308

Hargus NJ, Nigam A, Bertram EH, Patel MK, Evidence for a role of Nav1.6 in facilitating increases in neuronal hyperexcitability during epileptogenesis., 2013; Journal of neurophysiology. 110(5) 1144-57. PMID: 23741036 | PMCID: PMC3763090

Hargus NJ, Jennings C, Perez-Reyes E, Bertram EH, Patel MK, Enhanced actions of adenosine in medial entorhinal cortex layer II stellate neurons in temporal lobe epilepsy are mediated via A(1)-receptor activation., 2011; Epilepsia. 53(1) 168-76. PMID: 22126400 | PMCID: PMC3253213

Hargus NJ, Merrick EC, Nigam A, Kalmar CL, Baheti AR, Bertram EH, Patel MK, Temporal lobe epilepsy induces intrinsic alterations in Na channel gating in layer II medial entorhinal cortex neurons., 2010; Neurobiology of disease. 41(2) 361-76. PMID: 20946956 | PMCID: PMC3014455

Merrick EC, Kalmar CL, Snyder SL, Cusdin FS, Yu EJ, Sando JJ, Isakson BE, Jackson AP, Patel MK, The importance of serine 161 in the sodium channel beta3 subunit for modulation of Na(V)1.2 gating., 2009; Pflügers Archiv : European journal of physiology. 460(4) 743-53. PMID: 19806359 | PMCID: PMC2891377

Hargus NJ, Bertram EH, Patel MK, Adenosine A1 receptors presynaptically modulate excitatory synaptic input onto subiculum neurons., 2009; Brain research. 1280() 60-8. PMID: 19450566 | PMCID: PMC2731234

Jones PJ, Merrick EC, Batts TW, Hargus NJ, Wang Y, Stables JP, Bertram EH, Brown ML, Patel MK, Modulation of sodium channel inactivation gating by a novel lactam: implications for seizure suppression in chronic limbic epilepsy., 2008; The Journal of pharmacology and experimental therapeutics. 328(1) 201-12. PMID: 18952887 | PMCID: PMC2685906