弗兰克·米德尔顿博士

RESEARCH ABSTRACT

Research in the Middleton lab focuses on defining substrates of normal and abnormal motor and cognitive function. 这是通过执行高通量遗传来完成的, epigenetic, and functional genomic studies involving human subjects or animal and cellular models of various neuropsychiatric, neurodegenerative, 以及成瘾障碍. 最令人感兴趣的具体疾病包括自闭症, schizophrenia, ADHD, Parkinson's disease, alcohol abuse, 以及创伤性脑损伤. In addition to the use of similar analytical methods to study these conditions, another common underlying theme is the attempt to define their relationship to neural-immune responses. Thus, 神经-免疫轴也是实验室的一大兴趣所在, and this has been pursued through several collaborative efforts in studies of central and peripheral inflammatory and immune system alterations in these and other conditions, such as lupus, multiple sclerosis, 和寨卡病毒感染. While in the past, it might have been nearly impossible for one lab to simultaneously pursue research on so many different topics, with the advent of modern bioinformatic tools and systems biological methods, 这些综合方法现在被认为是非常有价值的. Indeed, comparisons across disorders can help define the specificity of the changes that are seen and may lead to the identification of novel biomarkers or therapeutic agents. As examples, recent publications from the lab describe several novel discoveries of DNA mutations causally linked to schizophrenia, or microRNA biomarkers in peripheral blood or saliva that are strongly associated with alcohol abuse or autism spectrum disorder. Students and postdoctoral fellows who are interested in the research performed in the lab will likely become well-versed in next generation sequencing, 比较解剖分析, 统计数据挖掘.

选定的出版物

Hicks SD, Jacob P, Middleton FA, Perez O, Gagnon Z. Distance running alters peripheral microRNAs implicated in metabolism, fluid balance, 肌凝蛋白以性别特异性的方式调节. Physiol Genomics. 2018 Jun 8. doi: 10.1152 / physiolgenomics.00035.2018. [印前Epub]PMID:29883262

Fernandes S, Srivastava N, Sudan R， Middleton FA， Shergill AK, Ryan JC, Kerr WG. SHIP1 Deficiency in Inflammatory Bowel Disease Is Associated With Severe Crohn's Disease and Peripheral T Cell Reduction. Front Immunol. 2018 May 22;9:1100. doi: 10.3389/fimmu.2018.01100. eCollection 2018.PMID:29872435

豪斯曼L，施韦策B， Middleton FA, Schulz JB. Reviewer selection biases editorial decisions on manuscripts. J Neurochem. 2018 Jan 27. doi: 10.1111/jnc.14314. [印前Epub] PMID:29377133

Afshari P, Yao WD, Middleton FA. Reduced Slc1a1 expression is associated with neuroinflammation and impaired sensorimotor gating and cognitive performance in mice: Implications for schizophrenia. PLoS One. 2017年9月8日;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. Contrast sensitivity to spatial gratings in moderate and dim light conditions in patients with diabetes in the absence of diabetic retinopathy. BMJ开放糖尿病护理. 2017年8月8日;5(1):e000408. doi: 10.1136 / bmjdrc - 2017 - 000408. eCollection 2017.PMID:28878937

Somasundaram R, Fernandes S, Deuring JJ, de Haar C, Kuipers EJ, Vogelaar L, Middleton FA， van der Woude CJ, Peppelenbosch MP, Kerr WG, fuller GM. Analysis of SHIP1 expression and activity in Crohn's disease patients. PLoS One. 2017年8月2日;12(8):e0182308. doi: 10.1371/journal.pone.0182308. eCollection 2017. PMID:28767696

Camargo Moreno M, Mooney SM， Middleton FA. Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder. PLoS One. 2017年7月19日;12(7):e0180873. doi: 10.1371/journal.pone.0180873. eCollection 2017.PMID:28723918

Lammert DB, Middleton FA，潘J, Olson EC, Howell BW. The de novo autism spectrum disorder RELN R2290C mutation reduces Reelin secretion and increases protein disulfide isomerase expression. J Neurochem. 2017年7月,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. Analysis of Shared Haplotypes amongst Palauans Maps Loci for Psychotic Disorders to 4q28 and 5q23-q31.Mol Neuropsychiatry. 2017年2月;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. 神经发育基因之间的联系, neuroanatomy, 以及2011年的超高风险精神病症状.2 deletion syndrome. J医学遗传学B神经精神病学遗传学. 2017年4月,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. A splicing-regulatory polymorphism in DRD2 disrupts ZRANB2 binding, impairs cognitive functioning and increases risk for schizophrenia in six Han Chinese samples. Mol Psychiatry. 2016年7月,21 (7):975 - 82. PubMed PMID: 26347318

Hicks SD, Ignacio C, Gentile K， Middleton FA. Salivary miRNA profiles identify children with autism spectrum disorder, 与适应性行为相关, and implicate ASD candidate genes involved in neurodevelopment. BMC Pediatr. 2016年4月22日;16(1):52. PubMed PMID: 27105825

Ignacio C, Hicks SD, Burke P, Lewis L, Szombathyne-Meszaros Z, Middleton FA. Alterations in serum microRNA in humans with alcohol use disorders impact cell proliferation and cell death pathways and predict structural and functional changes in brain. 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. White matter microstructural abnormalities of the cingulum bundle in youths with 22q11.2缺失综合征:与药物有关, 神经心理功能, 还有精神病的前驱症状. Schizophr Res. 2015年1月,161 (1):76 - 84. PubMed PMID: 25066496

Afshari P, Myles-Worsley M, Cohen OS, Tiobech J, Faraone SV, Byerley W, Middleton FA. Characterization of a novel mutation in SLC1A1 associated with schizophrenia. 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. Association between autism spectrum disorder in individuals with velocardiofacial (22q11.2缺失综合征和PRODH和COMT基因型. Psychiatr Genet. 2014年12月,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. Characterizing runs of homozygosity and their impact on risk for psychosis in a population isolate. J医学遗传学B神经精神病学遗传学. 2014年9月,165 b (6): 521 - 30. PubMed PMID: 24980794.

张詹姆斯，杨玲， Middleton FA杨磊，刘建军，刘建军. Autism-related behavioral phenotypes in an inbred rat substrain. Behav Brain Res. 2014年8月1日;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. 2011年白质异常.2 deletion syndrome: preliminary associations with the Nogo-66 receptor gene and symptoms of psychosis. Schizophr Res. 2014年1月,152(1):117 - 23所示. PubMed PMID: 24321711

Ignacio C, Mooney SM， Middleton FA. Effects of Acute Prenatal Exposure to Ethanol on microRNA Expression are Ameliorated by Social Enrichment. 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. Deletion at the SLC1A1 glutamate transporter gene co-segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family. J医学遗传学B神经精神病学遗传学. 2013年3月,162 b (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. 细胞增殖的评价, apoptosis, and DNA-repair genes as potential biomarkers for ethanol-induced CNS alterations. BMC Neurosci. 2012 Oct 25;13:128. PubMed PMID: 23095216