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Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin.

Hines RM, Maric HM, Hines DJ, Modgil A, Panzanelli P, Nakamura Y, Nathanson AJ, Cross A, Deeb T, Brandon NJ, Davies P, Fritschy JM, Schindelin H, Moss SJ.

Nat Commun. 2018 Aug 7;9(1):3130. doi: 10.1038/s41467-018-05481-1.


Corrigendum to "Challenges in the development of an M4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides" [Bioorg. Med. Chem. Lett. 27(23) (2017) 5179-5184].

Tarr JC, Wood MR, Noetzel MJ, Melancon BJ, Lamsal A, Luscombe VB, Rodriguez AL, Byers FW, Chang S, Cho HP, Engers DW, Jones CK, Niswender CM, Wood MW, Brandon NJ, Duggan ME, Jeffrey Conn P, Bridges TM, Lindsley CW.

Bioorg Med Chem Lett. 2018 Jul 31. pii: S0960-894X(18)30585-7. doi: 10.1016/j.bmcl.2018.07.022. [Epub ahead of print] No abstract available.


Developmental and genetic regulation of the human cortex transcriptome illuminate schizophrenia pathogenesis.

Jaffe AE, Straub RE, Shin JH, Tao R, Gao Y, Collado-Torres L, Kam-Thong T, Xi HS, Quan J, Chen Q, Colantuoni C, Ulrich WS, Maher BJ, Deep-Soboslay A; BrainSeq Consortium, Cross AJ, Brandon NJ, Leek JT, Hyde TM, Kleinman JE, Weinberger DR.

Nat Neurosci. 2018 Aug;21(8):1117-1125. doi: 10.1038/s41593-018-0197-y. Epub 2018 Jul 26.


Locally Reducing KCC2 Activity in the Hippocampus is Sufficient to Induce Temporal Lobe Epilepsy.

Kelley MR, Cardarelli RA, Smalley JL, Ollerhead TA, Andrew PM, Brandon NJ, Deeb TZ, Moss SJ.

EBioMedicine. 2018 Jun;32:62-71. doi: 10.1016/j.ebiom.2018.05.029. Epub 2018 Jun 5.


Small molecule inducers of ABCA1 and apoE that act through indirect activation of the LXR pathway.

Fan J, Zhao RQ, Parro C, Zhao W, Chou HY, Robert J, Deeb TZ, Raynoschek C, Barichievy S, Engkvist O, Maresca M, Hicks R, Meuller J, Moss SJ, Brandon NJ, Wood MW, Kulic I, Wellington CL.

J Lipid Res. 2018 May;59(5):830-842. doi: 10.1194/jlr.M081851. Epub 2018 Mar 21.


The small molecule CLP257 does not modify activity of the K+-Cl- co-transporter KCC2 but does potentiate GABAA receptor activity.

Cardarelli RA, Jones K, Pisella LI, Wobst HJ, McWilliams LJ, Sharpe PM, Burnham MP, Baker DJ, Chudotvorova I, Guyot J, Silayeva L, Morrow DH, Dekker N, Zicha S, Davies PA, Holenz J, Duggan ME, Dunlop J, Mather RJ, Wang Q, Medina I, Brandon NJ, Deeb TZ, Moss SJ.

Nat Med. 2017 Dec 7;23(12):1394-1396. doi: 10.1038/nm.4442. No abstract available.


Molecular architecture of potassium chloride co-transporter KCC2.

Agez M, Schultz P, Medina I, Baker DJ, Burnham MP, Cardarelli RA, Conway LC, Garnier K, Geschwindner S, Gunnarsson A, McCall EJ, Frechard A, Audebert S, Deeb TZ, Moss SJ, Brandon NJ, Wang Q, Dekker N, Jawhari A.

Sci Rep. 2017 Nov 28;7(1):16452. doi: 10.1038/s41598-017-15739-1.


X-ray Characterization and Structure-Based Optimization of Striatal-Enriched Protein Tyrosine Phosphatase Inhibitors.

Witten MR, Wissler L, Snow M, Geschwindner S, Read JA, Brandon NJ, Nairn AC, Lombroso PJ, Käck H, Ellman JA.

J Med Chem. 2017 Nov 22;60(22):9299-9319. doi: 10.1021/acs.jmedchem.7b01292. Epub 2017 Nov 8.


Verbal working memory and functional large-scale networks in schizophrenia.

Dauvermann MR, Moorhead TW, Watson AR, Duff B, Romaniuk L, Hall J, Roberts N, Lee GL, Hughes ZA, Brandon NJ, Whitcher B, Blackwood DH, McIntosh AM, Lawrie SM.

Psychiatry Res Neuroimaging. 2017 Oct 23;270:86-96. doi: 10.1016/j.pscychresns.2017.10.004. [Epub ahead of print]


N-Ethylmaleimide increases KCC2 cotransporter activity by modulating transporter phosphorylation.

Conway LC, Cardarelli RA, Moore YE, Jones K, McWilliams LJ, Baker DJ, Burnham MP, Bürli RW, Wang Q, Brandon NJ, Moss SJ, Deeb TZ.

J Biol Chem. 2017 Dec 29;292(52):21253-21263. doi: 10.1074/jbc.M117.817841. Epub 2017 Nov 1.


Challenges in the development of an M4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides.

Tarr JC, Wood MR, Noetzel MJ, Melancon BJ, Lamsal A, Luscombe VB, Rodriguez AL, Byers FW, Chang S, Cho HP, Engers DW, Jones CK, Niswender CM, Wood MW, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW.

Bioorg Med Chem Lett. 2017 Dec 1;27(23):5179-5184. doi: 10.1016/j.bmcl.2017.10.053. Epub 2017 Oct 24. Erratum in: Bioorg Med Chem Lett. 2018 Jul 31;:.


Estradiol modulates the efficacy of synaptic inhibition by decreasing the dwell time of GABAA receptors at inhibitory synapses.

Mukherjee J, Cardarelli RA, Cantaut-Belarif Y, Deeb TZ, Srivastava DP, Tyagarajan SK, Pangalos MN, Triller A, Maguire J, Brandon NJ, Moss SJ.

Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):11763-11768. doi: 10.1073/pnas.1705075114. Epub 2017 Oct 16.


Current Understanding of PDE10A in the Modulation of Basal Ganglia Circuitry.

Schülke JP, Brandon NJ.

Adv Neurobiol. 2017;17:15-43. doi: 10.1007/978-3-319-58811-7_2. Review.


Seizing Control of KCC2: A New Therapeutic Target for Epilepsy.

Moore YE, Kelley MR, Brandon NJ, Deeb TZ, Moss SJ.

Trends Neurosci. 2017 Sep;40(9):555-571. doi: 10.1016/j.tins.2017.06.008. Epub 2017 Aug 10. Review.


Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154.

Gould RW, Grannan MD, Gunter BW, Ball J, Bubser M, Bridges TM, Wess J, Wood MW, Brandon NJ, Duggan ME, Niswender CM, Lindsley CW, Conn PJ, Jones CK.

Neuropharmacology. 2018 Jan;128:492-502. doi: 10.1016/j.neuropharm.2017.07.013. Epub 2017 Jul 17.


FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system.

Yalla K, Elliott C, Day JP, Findlay J, Barratt S, Hughes ZA, Wilson L, Whiteley E, Popiolek M, Li Y, Dunlop J, Killick R, Adams DR, Brandon NJ, Houslay MD, Hao B, Baillie GS.

Mol Psychiatry. 2018 May;23(5):1278-1286. doi: 10.1038/mp.2017.138. Epub 2017 Jul 20.


Challenges in the development of an M4 PAM preclinical candidate: The discovery, SAR, and in vivo characterization of a series of 3-aminoazetidine-derived amides.

Tarr JC, Wood MR, Noetzel MJ, Bertron JL, Weiner RL, Rodriguez AL, Lamsal A, Byers FW, Chang S, Cho HP, Jones CK, Niswender CM, Wood MW, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW.

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2990-2995. doi: 10.1016/j.bmcl.2017.05.014. Epub 2017 May 6.


Truncation of the TAR DNA-binding protein 43 is not a prerequisite for cytoplasmic relocalization, and is suppressed by caspase inhibition and by introduction of the A90V sequence variant.

Wobst HJ, Delsing L, Brandon NJ, Moss SJ.

PLoS One. 2017 May 16;12(5):e0177181. doi: 10.1371/journal.pone.0177181. eCollection 2017.


Altered expression of histamine signaling genes in autism spectrum disorder.

Wright C, Shin JH, Rajpurohit A, Deep-Soboslay A, Collado-Torres L, Brandon NJ, Hyde TM, Kleinman JE, Jaffe AE, Cross AJ, Weinberger DR.

Transl Psychiatry. 2017 May 9;7(5):e1126. doi: 10.1038/tp.2017.87.


Optimization of M4 positive allosteric modulators (PAMs): The discovery of VU0476406, a non-human primate in vivo tool compound for translational pharmacology.

Melancon BJ, Wood MR, Noetzel MJ, Nance KD, Engelberg EM, Han C, Lamsal A, Chang S, Cho HP, Byers FW, Bubser M, Jones CK, Niswender CM, Wood MW, Engers DW, Wu D, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW.

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2296-2301. doi: 10.1016/j.bmcl.2017.04.043. Epub 2017 Apr 13.


Cytoplasmic Relocalization of TAR DNA-Binding Protein 43 Is Not Sufficient to Reproduce Cellular Pathologies Associated with ALS In vitro.

Wobst HJ, Wesolowski SS, Chadchankar J, Delsing L, Jacobsen S, Mukherjee J, Deeb TZ, Dunlop J, Brandon NJ, Moss SJ.

Front Mol Neurosci. 2017 Feb 24;10:46. doi: 10.3389/fnmol.2017.00046. eCollection 2017.


Deficits in the activity of presynaptic γ-aminobutyric acid type B receptors contribute to altered neuronal excitability in fragile X syndrome.

Kang JY, Chadchankar J, Vien TN, Mighdoll MI, Hyde TM, Mather RJ, Deeb TZ, Pangalos MN, Brandon NJ, Dunlop J, Moss SJ.

J Biol Chem. 2017 Apr 21;292(16):6621-6632. doi: 10.1074/jbc.M116.772541. Epub 2017 Feb 17.


Discovery of VU0467485/AZ13713945: An M4 PAM Evaluated as a Preclinical Candidate for the Treatment of Schizophrenia.

Wood MR, Noetzel MJ, Melancon BJ, Poslusney MS, Nance KD, Hurtado MA, Luscombe VB, Weiner RL, Rodriguez AL, Lamsal A, Chang S, Bubser M, Blobaum AL, Engers DW, Niswender CM, Jones CK, Brandon NJ, Wood MW, Duggan ME, Conn PJ, Bridges TM, Lindsley CW.

ACS Med Chem Lett. 2016 Dec 16;8(2):233-238. doi: 10.1021/acsmedchemlett.6b00461. eCollection 2017 Feb 9.


The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review.

Dahoun T, Trossbach SV, Brandon NJ, Korth C, Howes OD.

Transl Psychiatry. 2017 Jan 31;7(1):e1015. doi: 10.1038/tp.2016.282. Review.


Effects of environmental risks and polygenic loading for schizophrenia on cortical thickness.

Neilson E, Bois C, Gibson J, Duff B, Watson A, Roberts N, Brandon NJ, Dunlop J, Hall J, McIntosh AM, Whalley HC, Lawrie SM.

Schizophr Res. 2017 Jun;184:128-136. doi: 10.1016/j.schres.2016.12.011. Epub 2016 Dec 15.


Challenges in the development of an M4 PAM in vivo tool compound: The discovery of VU0467154 and unexpected DMPK profiles of close analogs.

Wood MR, Noetzel MJ, Poslusney MS, Melancon BJ, Tarr JC, Lamsal A, Chang S, Luscombe VB, Weiner RL, Cho HP, Bubser M, Jones CK, Niswender CM, Wood MW, Engers DW, Brandon NJ, Duggan ME, Conn PJ, Bridges TM, Lindsley CW.

Bioorg Med Chem Lett. 2017 Jan 15;27(2):171-175. doi: 10.1016/j.bmcl.2016.11.086. Epub 2016 Nov 30.


Misassembly of full-length Disrupted-in-Schizophrenia 1 protein is linked to altered dopamine homeostasis and behavioral deficits.

Trossbach SV, Bader V, Hecher L, Pum ME, Masoud ST, Prikulis I, Schäble S, de Souza Silva MA, Su P, Boulat B, Chwiesko C, Poschmann G, Stühler K, Lohr KM, Stout KA, Oskamp A, Godsave SF, Müller-Schiffmann A, Bilzer T, Steiner H, Peters PJ, Bauer A, Sauvage M, Ramsey AJ, Miller GW, Liu F, Seeman P, Brandon NJ, Huston JP, Korth C.

Mol Psychiatry. 2016 Nov;21(11):1561-1572. doi: 10.1038/mp.2015.194. Epub 2016 Jan 12.


Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function.

Thomson PA, Duff B, Blackwood DH, Romaniuk L, Watson A, Whalley HC, Li X, Dauvermann MR, Moorhead TW, Bois C, Ryan NM, Redpath H, Hall L, Morris SW, van Beek EJ, Roberts N, Porteous DJ, St Clair D, Whitcher B, Dunlop J, Brandon NJ, Hughes ZA, Hall J, McIntosh A, Lawrie SM.

NPJ Schizophr. 2016 Aug 10;2:16024. doi: 10.1038/npjschz.2016.24. eCollection 2016.


SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex.

Tankou S, Ishii K, Elliott C, Yalla KC, Day JP, Furukori K, Kubo KI, Brandon NJ, Tang Q, Hayward G, Nakajima K, Houslay MD, Kamiya A, Baillie G, Ishizuka K, Sawa A.

Mol Neuropsychiatry. 2016 May;2(1):20-27. Epub 2016 Mar 15.


Discovery and SAR of a novel series of potent, CNS penetrant M4 PAMs based on a non-enolizable ketone core: Challenges in disposition.

Wood MR, Noetzel MJ, Tarr JC, Rodriguez AL, Lamsal A, Chang S, Foster JJ, Smith E, Chase P, Hodder PS, Engers DW, Niswender CM, Brandon NJ, Wood MW, Duggan ME, Conn PJ, Bridges TM, Lindsley CW.

Bioorg Med Chem Lett. 2016 Sep 1;26(17):4282-6. doi: 10.1016/j.bmcl.2016.07.042. Epub 2016 Jul 21.


A human-specific AS3MT isoform and BORCS7 are molecular risk factors in the 10q24.32 schizophrenia-associated locus.

Li M, Jaffe AE, Straub RE, Tao R, Shin JH, Wang Y, Chen Q, Li C, Jia Y, Ohi K, Maher BJ, Brandon NJ, Cross A, Chenoweth JG, Hoeppner DJ, Wei H, Hyde TM, McKay R, Kleinman JE, Weinberger DR.

Nat Med. 2016 Jun;22(6):649-56. doi: 10.1038/nm.4096. Epub 2016 May 9.


Compromising KCC2 transporter activity enhances the development of continuous seizure activity.

Kelley MR, Deeb TZ, Brandon NJ, Dunlop J, Davies PA, Moss SJ.

Neuropharmacology. 2016 Sep;108:103-10. doi: 10.1016/j.neuropharm.2016.04.029. Epub 2016 Apr 21.


Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy.

Diggle CP, Sukoff Rizzo SJ, Popiolek M, Hinttala R, Schülke JP, Kurian MA, Carr IM, Markham AF, Bonthron DT, Watson C, Sharif SM, Reinhart V, James LC, Vanase-Frawley MA, Charych E, Allen M, Harms J, Schmidt CJ, Ng J, Pysden K, Strick C, Vieira P, Mankinen K, Kokkonen H, Kallioinen M, Sormunen R, Rinne JO, Johansson J, Alakurtti K, Huilaja L, Hurskainen T, Tasanen K, Anttila E, Marques TR, Howes O, Politis M, Fahiminiya S, Nguyen KQ, Majewski J, Uusimaa J, Sheridan E, Brandon NJ.

Am J Hum Genet. 2016 Apr 7;98(4):735-43. doi: 10.1016/j.ajhg.2016.03.015.


Searching for cognitive enhancement in the Morris water maze: better and worse performance in D-amino acid oxidase knockout (Dao(-/-)) mice.

Pritchett D, Taylor AM, Barkus C, Engle SJ, Brandon NJ, Sharp T, Foster RG, Harrison PJ, Peirson SN, Bannerman DM.

Eur J Neurosci. 2016 Apr;43(7):979-89. doi: 10.1111/ejn.13192. Epub 2016 Mar 23.


Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models.

Haggarty SJ, Silva MC, Cross A, Brandon NJ, Perlis RH.

Mol Cell Neurosci. 2016 Jun;73:104-15. doi: 10.1016/j.mcn.2016.01.011. Epub 2016 Jan 28. Review.


Early postnatal GABAA receptor modulation reverses deficits in neuronal maturation in a conditional neurodevelopmental mouse model of DISC1.

Saito A, Taniguchi Y, Rannals MD, Merfeld EB, Ballinger MD, Koga M, Ohtani Y, Gurley DA, Sedlak TW, Cross A, Moss SJ, Brandon NJ, Maher BJ, Kamiya A.

Mol Psychiatry. 2016 Oct;21(10):1449-59. doi: 10.1038/mp.2015.203. Epub 2016 Jan 5.


Identification of Phosphorylation Consensus Sequences and Endogenous Neuronal Substrates of the Psychiatric Risk Kinase TNIK.

Wang Q, Amato SP, Rubitski DM, Hayward MM, Kormos BL, Verhoest PR, Xu L, Brandon NJ, Ehlers MD.

J Pharmacol Exp Ther. 2016 Feb;356(2):410-23. doi: 10.1124/jpet.115.229880. Epub 2015 Dec 8.


Compromising the phosphodependent regulation of the GABAAR β3 subunit reproduces the core phenotypes of autism spectrum disorders.

Vien TN, Modgil A, Abramian AM, Jurd R, Walker J, Brandon NJ, Terunuma M, Rudolph U, Maguire J, Davies PA, Moss SJ.

Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):14805-10. doi: 10.1073/pnas.1514657112. Epub 2015 Nov 16.


State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 - Relation to antipsychotic-like drug effects.

Gould RW, Nedelcovych MT, Gong X, Tsai E, Bubser M, Bridges TM, Wood MR, Duggan ME, Brandon NJ, Dunlop J, Wood MW, Ivarsson M, Noetzel MJ, Daniels JS, Niswender CM, Lindsley CW, Conn PJ, Jones CK.

Neuropharmacology. 2016 Mar;102:244-53. doi: 10.1016/j.neuropharm.2015.11.016. Epub 2015 Nov 23.


The cellular target of antidepressants.

Brandon NJ, McKay R.

Nat Neurosci. 2015 Nov;18(11):1537-8. doi: 10.1038/nn.4144. No abstract available.


Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity.

Whalley HC, Dimitrova R, Sprooten E, Dauvermann MR, Romaniuk L, Duff B, Watson AR, Moorhead B, Bastin M, Semple SI, Giles S, Hall J, Thomson P, Roberts N, Hughes ZA, Brandon NJ, Dunlop J, Whitcher B, Blackwood DH, McIntosh AM, Lawrie SM.

PLoS One. 2015 Jun 23;10(6):e0130900. doi: 10.1371/journal.pone.0130900. eCollection 2015.


Selective inhibition of KCC2 leads to hyperexcitability and epileptiform discharges in hippocampal slices and in vivo.

Sivakumaran S, Cardarelli RA, Maguire J, Kelley MR, Silayeva L, Morrow DH, Mukherjee J, Moore YE, Mather RJ, Duggan ME, Brandon NJ, Dunlop J, Zicha S, Moss SJ, Deeb TZ.

J Neurosci. 2015 May 27;35(21):8291-6. doi: 10.1523/JNEUROSCI.5205-14.2015.


Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1.

Dawson N, Kurihara M, Thomson DM, Winchester CL, McVie A, Hedde JR, Randall AD, Shen S, Seymour PA, Hughes ZA, Dunlop J, Brown JT, Brandon NJ, Morris BJ, Pratt JA.

Transl Psychiatry. 2015 May 19;5:e569. doi: 10.1038/tp.2015.60.


d-amino acid oxidase knockout (Dao(-/-) ) mice show enhanced short-term memory performance and heightened anxiety, but no sleep or circadian rhythm disruption.

Pritchett D, Hasan S, Tam SK, Engle SJ, Brandon NJ, Sharp T, Foster RG, Harrison PJ, Bannerman DM, Peirson SN.

Eur J Neurosci. 2015 May;41(9):1167-79. doi: 10.1111/ejn.12880. Epub 2015 Mar 27.


Organization of TNIK in dendritic spines.

Burette AC, Phend KD, Burette S, Lin Q, Liang M, Foltz G, Taylor N, Wang Q, Brandon NJ, Bates B, Ehlers MD, Weinberg RJ.

J Comp Neurol. 2015 Sep 1;523(13):1913-24. doi: 10.1002/cne.23770. Epub 2015 Jul 1.


KCC2 activity is critical in limiting the onset and severity of status epilepticus.

Silayeva L, Deeb TZ, Hines RM, Kelley MR, Munoz MB, Lee HH, Brandon NJ, Dunlop J, Maguire J, Davies PA, Moss SJ.

Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3523-8. doi: 10.1073/pnas.1415126112. Epub 2015 Mar 2.


Schizophrenia drug discovery and development in an evolving era: are new drug targets fulfilling expectations?

Dunlop J, Brandon NJ.

J Psychopharmacol. 2015 Feb;29(2):230-8. doi: 10.1177/0269881114565806. Epub 2015 Jan 13. Review.


Chemoproteomics demonstrates target engagement and exquisite selectivity of the clinical phosphodiesterase 10A inhibitor MP-10 in its native environment.

Schülke JP, McAllister LA, Geoghegan KF, Parikh V, Chappie TA, Verhoest PR, Schmidt CJ, Johnson DS, Brandon NJ.

ACS Chem Biol. 2014 Dec 19;9(12):2823-32. doi: 10.1021/cb500671j. Epub 2014 Oct 20.


DISC1 regulates trafficking and processing of APP and Aβ generation.

Shahani N, Seshadri S, Jaaro-Peled H, Ishizuka K, Hirota-Tsuyada Y, Wang Q, Koga M, Sedlak TW, Korth C, Brandon NJ, Kamiya A, Subramaniam S, Tomoda T, Sawa A.

Mol Psychiatry. 2015 Jul;20(7):874-9. doi: 10.1038/mp.2014.100. Epub 2014 Sep 16.

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