Frank Middleton, PhD

RESEARCH ABSTRACT

米德尔顿实验室的研究重点是定义正常和异常运动和认知功能的基础. This is accomplished by performing high-throughput genetic, epigenetic, 功能基因组研究涉及人类受试者或动物和各种神经精神细胞模型, neurodegenerative, and addictive disorders. The specific disorders of most interest include autism, schizophrenia, ADHD, Parkinson's disease, alcohol abuse, and traumatic brain injury. 除了使用类似的分析方法来研究这些条件外, 另一个共同的潜在主题是试图定义它们与神经免疫反应的关系. Thus, the neural-immune axis forms a major lab interest as well, 这是通过几项合作研究来实现的在这些和其他情况下的中枢和外周炎症和免疫系统改变, such as lupus, multiple sclerosis, and Zika virus infection. While in the past, 一个实验室同时从事这么多不同主题的研究几乎是不可能的, 随着现代生物信息学工具和系统的出现，生物方法, these integrated approaches are now seen as highly valuable. Indeed, 跨疾病的比较可以帮助确定所见变化的特异性，并可能导致鉴定新的生物标志物或治疗剂. As examples, 该实验室最近发表的文章描述了几项与精神分裂症有因果关系的DNA突变的新发现, 或外周血或唾液中的microRNA生物标志物与酒精滥用或自闭症谱系障碍密切相关. 对实验室进行的研究感兴趣的学生和博士后研究员可能会精通下一代测序, comparative anatomical analysis, and statistical data mining.

Selected Publications

Hicks SD, Jacob P, Middleton FA, Perez O, Gagnon Z. 长跑改变了与代谢有关的外周microrna, fluid balance, and myosin regulation in a sex-specific manner. Physiol Genomics. 2018 Jun 8. doi: 10.1152/physiolgenomics.00035.2018. [Epub ahead of print]PMID:29883262

Fernandes S, Srivastava N, Sudan R, Middleton FA, Shergill AK, Ryan JC, Kerr WG. 炎性肠病患者SHIP1缺乏与严重克罗恩病和外周T细胞减少有关. Front Immunol. 2018 May 22;9:1100. doi: 10.3389/fimmu.2018.01100. eCollection 2018.PMID:29872435

Hausmann L, Schweitzer B, Middleton FA, Schulz JB. 审稿人的选择会影响稿件的编辑决策. J Neurochem. 2018 Jan 27. doi: 10.1111/jnc.14314. [Epub ahead of print] PMID:29377133

Afshari P, Yao WD, Middleton FA. Slc1a1表达减少与小鼠神经炎症、感觉运动门控和认知能力受损有关:对精神分裂症的影响. PLoS One. 2017 Sep 8;12(9):e0183854. doi: 10.1371/journal.pone.0183854. eCollection 2017.PMID:28886095

Safi S, Rahimi A, Raeesi A, Safi H, Aghazadeh Amiri M, Malek M, Yaseri M, Haeri M， Middleton FA, Solessio E, Ahmadieh H. 无糖尿病视网膜病变的糖尿病患者在中暗光照条件下空间光栅的对比敏感度. BMJ Open Diabetes Res Care. 2017 Aug 8;5(1):e000408. doi: 10.1136/bmjdrc-2017-000408. eCollection 2017.PMID:28878937

苏松达兰R, Fernandes S, Deuring JJ, de Haar C, Kuipers EJ, Vogelaar L， Middleton FA, van der Woude CJ, Peppelenbosch MP, Kerr WG, Fuhler GM. 克罗恩病患者SHIP1表达及活性分析. PLoS One. 2017 Aug 2;12(8):e0182308. doi: 10.1371/journal.pone.0182308. eCollection 2017. PMID:28767696

Camargo Moreno M, Mooney SM, Middleton FA. 胎儿酒精谱系障碍发育小鼠模型中乙醇暴露后p53依赖基因组反应的异质性. PLoS One. 2017 Jul 19;12(7):e0180873. doi: 10.1371/journal.pone.0180873. eCollection 2017.PMID:28723918

Lammert DB, Middleton FA, Pan J, Olson EC, Howell BW. 新生自闭症谱系障碍RELN R2290C突变减少Reelin分泌并增加蛋白二硫异构酶表达. J Neurochem. 2017 Jul;142(1):89-102. doi: 10.1111/jnc.14045. Epub 2017 May 18.PMID:28419454

Bodea CA, Middleton FA, Melhem NM, Klei L, Song Y, Tiobech J, Marumoto P, Yano V, Faraone SV, Roeder K, Myles-Worsley M, Devlin B, Byerley W. 帕劳人共享单倍型分析将精神疾病基因座定位于4q28和5q23-q31.Mol Neuropsychiatry. 2017 Feb;2(4):173-184. doi: 10.1159/000450726. Epub 2016 Oct 12. PMID:28277564

Thompson CA, Karelis J, Middleton FA， Gentile K, Coman IL, Radoeva PD, Mehta R, Fremont WP, Antshel KM, Faraone SV, Kates WR. Associations between neurodevelopmental genes, neuroanatomy, and ultra high risk symptoms of psychosis in 22q11.2 deletion syndrome. Am J Med Genet B Neuropsychiatr Genet. 2017 Apr;174(3):295-314. doi: 10.1002/ajmg.b.32515. Epub 2017 Jan 31.PMID:28139055

Cohen OS, Weickert TW, Hess JL, Paish LM, McCoy SY, Rothmond DA, Galletly C, Liu D, Weinberg DD, Huang XF, Xu Q, Shen Y, Zhang D, Yue W, Yan J, Wang L, Lu T, He L, Shi Y, Xu M, Che R, Tang W, Chen CH, Chang WH, Hwu HG, Liu CM, Liu YL, Wen CC, Fann CS, Chang CC, Kanazawa T, Middleton FA, Duncan TM, Faraone SV, Weickert CS, Tsuang MT, Glatt SJ. DRD2中的剪接调控多态性会破坏ZRANB2的结合, 损害认知功能，增加6个汉族样本患精神分裂症的风险. Mol Psychiatry. 2016 Jul;21(7):975-82. PubMed PMID: 26347318

Hicks SD, Ignacio C, Gentile K, Middleton FA. 唾液miRNA谱可识别自闭症谱系障碍儿童, correlate with adaptive behavior, 并暗示ASD候选基因参与神经发育. BMC Pediatr. 2016 Apr 22;16(1):52. PubMed PMID: 27105825

Ignacio C, Hicks SD, Burke P, Lewis L, Szombathyne-Meszaros Z， Middleton FA. 酒精使用障碍患者血清microRNA的改变影响细胞增殖和细胞死亡途径，并预测大脑结构和功能的变化. BMC Neurosci. 2015 Sep 5;16:55. PubMed PMID: 26341662

Kates WR, Olszewski AK, Gnirke MH, Kikinis Z, Nelson J, Antshel KM, Fremont W, Radoeva PD, Middleton FA, Shenton ME, Coman IL. 22q11青少年扣带束白质显微结构异常.2 deletion syndrome: associations with medication, neuropsychological function, and prodromal symptoms of psychosis. Schizophr Res. 2015 Jan;161(1):76-84. PubMed PMID: 25066496

Afshari P, Myles-Worsley M, Cohen OS, Tiobech J, Faraone SV, Byerley W， Middleton FA. 与精神分裂症相关的SLC1A1基因新突变的特征. Mol Neuropsychiatry. 2015;1(3):125-144. PubMed PMID: 26380821

Radoeva PD, Coman IL, Salazar CA, Gentile KL, Higgins AM, Middleton FA, Antshel KM, Fremont W, Shprintzen RJ, Morrow BE, Kates WR. 自闭症谱系障碍与心面疾速个体之间的关系(22q11).2 deletion) syndrome and PRODH and COMT genotypes. Psychiatr Genet. 2014 Dec;24(6):269-72. PubMed PMID: 25325218

Melhem NM, Lu C, Dresbold C, Middleton FA, Klei L, Wood S, Faraone SV, Vinogradov S, Tiobech J, Yano V, Roeder K, Byerley W, Myles-Worsley M, Devlin B. 在孤立人群中描述纯合子的运行及其对精神病风险的影响. Am J Med Genet B Neuropsychiatr Genet. 2014 Sep;165B(6):521-30. PubMed PMID: 24980794.

Zhang-James Y, Yang L, Middleton FA, Yang L, Patak J, Faraone SV. 一个近交系大鼠亚系自闭症相关行为表型. Behav Brain Res. 2014 Aug 1;269:103-14. doi: 10.1016/j.bbr.2014.04.035. Epub 2014 Apr 26. PubMed PMID

Perlstein MD, Chohan MR, Coman IL, Antshel KM, Fremont WP, Gnirke MH, Kikinis Z， Middleton FA, Radoeva PD, Shenton ME, Kates WR. White matter abnormalities in 22q11.2缺失综合征:与Nogo-66受体基因和精神病症状的初步关联. Schizophr Res. 2014 Jan;152(1):117-23. PubMed PMID: 24321711

Ignacio C, Mooney SM, Middleton FA. 急性产前乙醇暴露对microRNA表达的影响通过社会富集得到改善. Front Pediatr. 2014 Sep 24;2:103. PubMed PMID: 25309888

Myles-Worsley M, Tiobech J, Browning SR, Korn J, Goodman S, Gentile K, Melhem N, Byerley W, Faraone SV, Middleton FA. SLC1A1谷氨酸转运蛋白基因缺失与精神分裂症和双相情感分裂障碍共分离在一个五代家族中存在. Am J Med Genet B Neuropsychiatr Genet. 2013 Mar;162B(2):87-95. PubMed PMID: 23341099

Hicks SD, Lewis L, Ritchie J, Burke P, Abdul-Malak Y, Adackapara N, Canfield K, Shwarts E, Gentile K, Meszaros ZS, Middleton FA. Evaluation of cell proliferation, apoptosis, 以及dna修复基因作为乙醇诱导中枢神经系统改变的潜在生物标志物. BMC Neurosci. 2012 Oct 25;13:128. PubMed PMID: 23095216