 Morizono, Hiroki
| Title | Associate Research Professor |
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| Institution | Childrens National Medical Center |
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| Department | Center for Genetic Medicine |
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| Address | 111 Michigan Ave NW
Washington DC 20010
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| vCard | Download vCard |
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 Overview My lab is interested in nitrogen metabolism, a central process for converting nutrients and waste products into the building blocks of cells, energy production and metabolic detoxification. We use the vertebrate urea cycle and bacterial arginine biosynthesis pathways as our model systems. Our research seeks to categorize and understand the biological scales and mechanisms by which mutations in urea cycle enzymes cause disease, and to develop therapies to treat disorders of nitrogen metabolism. I have a deep-seated interest in the relationships between sequence, structure, and function of proteins, particularly novel variations of questons including how does an amino acid sequence fold into a particular three dimensional shape? What are the forces that hold the protein in this folded shape? Why does this conformation catalyze a chemical reaction? Which regions of a protein are affected when mutations occur, and how do mutations affect its catalytic activity? Insights into these questions let us predict if an inherited mutation might be deleterious, and are also forms the basis for understanding how the different proteins and enzymes interact in our cells and our bodies.
Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
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Wang L, Bell P, Morizono H, He Z, Pumbo E, Yu H, White J, Batshaw ML, Wilson JM. AAV gene therapy corrects OTC deficiency and prevents liver fibrosis in aged OTC-knock out heterozygous mice. Mol Genet Metab. 2017 Apr; 120(4):299-305. PMID: 28283349.
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Yang Y, Wang L, Bell P, McMenamin D, He Z, White J, Yu H, Xu C, Morizono H, Musunuru K, Batshaw ML, Wilson JM. A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol. 2016 Mar; 34(3):334-8. PMID: 26829317; PMCID: PMC4786489.
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Caldovic L, Abdikarim I, Narain S, Tuchman M, Morizono H. Genotype-Phenotype Correlations in Ornithine Transcarbamylase Deficiency: A Mutation Update. J Genet Genomics. 2015 May 20; 42(5):181-94. PMID: 26059767; PMCID: PMC4565140.
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Ko KD, El-Ghazawi T, Kim D, Morizono H. Predicting the severity of motor neuron disease progression using electronic health record data with a cloud computing Big Data approach. IEEE Symp Comput Intell Bioinforma Comput Biol Proc. 2014 May; 2014. PMID: 25580472.
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Senkevitch E, Cabrera-Luque J, Morizono H, Caldovic L, Tuchman M. A novel biochemically salvageable animal model of hyperammonemia devoid of N-acetylglutamate synthase. Mol Genet Metab. 2012 Jun; 106(2):160-8. PMID: 22503289; PMCID: PMC3356441.
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Wang L, Morizono H, Lin J, Bell P, Jones D, McMenamin D, Yu H, Batshaw ML, Wilson JM. Preclinical evaluation of a clinical candidate AAV8 vector for ornithine transcarbamylase (OTC) deficiency reveals functional enzyme from each persisting vector genome. Mol Genet Metab. 2012 Feb; 105(2):203-11. PMID: 22133298; PMCID: PMC3270700.
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Calcedo R, Morizono H, Wang L, McCarter R, He J, Jones D, Batshaw ML, Wilson JM. Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clin Vaccine Immunol. 2011 Sep; 18(9):1586-8. PMID: 21775517; PMCID: PMC3165215.
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Caldovic L, Ah Mew N, Shi D, Morizono H, Yudkoff M, Tuchman M. N-acetylglutamate synthase: structure, function and defects. Mol Genet Metab. 2010; 100 Suppl 1:S13-9. PMID: 20303810; PMCID: PMC2876818.
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Wang L, Calcedo R, Wang H, Bell P, Grant R, Vandenberghe LH, Sanmiguel J, Morizono H, Batshaw ML, Wilson JM. The pleiotropic effects of natural AAV infections on liver-directed gene transfer in macaques. Mol Ther. 2010 Jan; 18(1):126-34. PMID: 19888196; PMCID: PMC2839221.
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Wang L, Wang H, Bell P, McCarter RJ, He J, Calcedo R, Vandenberghe LH, Morizono H, Batshaw ML, Wilson JM. Systematic evaluation of AAV vectors for liver directed gene transfer in murine models. Mol Ther. 2010 Jan; 18(1):118-25. PMID: 19861950; PMCID: PMC2839210.
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Min L, Jin Z, Caldovic L, Morizono H, Allewell NM, Tuchman M, Shi D. Mechanism of allosteric inhibition of N-acetyl-L-glutamate synthase by L-arginine. J Biol Chem. 2009 Feb 20; 284(8):4873-80. PMID: 19095660; PMCID: PMC2643497.
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Haskins N, Panglao M, Qu Q, Majumdar H, Cabrera-Luque J, Morizono H, Tuchman M, Caldovic L. Inversion of allosteric effect of arginine on N-acetylglutamate synthase, a molecular marker for evolution of tetrapods. BMC Biochem. 2008 Sep 18; 9:24. PMID: 18801197; PMCID: PMC2566978.
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Maletkovic J, Schiffmann R, Gorospe JR, Gordon ES, Mintz M, Hoffman EP, Alper G, Lynch DR, Singhal BS, Harding C, Amartino H, Brown CM, Chan A, Renaud D, Geraghty M, Jensen L, Senbil N, Kadom N, Nazarian J. Genetic and clinical heterogeneity in eIF2B-related disorder. J Child Neurol. 2008 Feb; 23(2):205-15. PMID: 18263758.
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Shi D, Sagar V, Jin Z, Yu X, Caldovic L, Morizono H, Allewell NM, Tuchman M. The crystal structure of N-acetyl-L-glutamate synthase from Neisseria gonorrhoeae provides insights into mechanisms of catalysis and regulation. J Biol Chem. 2008 Mar 14; 283(11):7176-84. PMID: 18184660; PMCID: PMC4099063.
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Caldovic L, Morizono H, Tuchman M. Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene. Hum Mutat. 2007 Aug; 28(8):754-9. PMID: 17421020.
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Shi D, Yu X, Cabrera-Luque J, Chen TY, Roth L, Morizono H, Allewell NM, Tuchman M. A single mutation in the active site swaps the substrate specificity of N-acetyl-L-ornithine transcarbamylase and N-succinyl-L-ornithine transcarbamylase. Protein Sci. 2007 Aug; 16(8):1689-99. PMID: 17600144; PMCID: PMC2203365.
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Qu Q, Morizono H, Shi D, Tuchman M, Caldovic L. A novel bifunctional N-acetylglutamate synthase-kinase from Xanthomonas campestris that is closely related to mammalian N-acetylglutamate synthase. BMC Biochem. 2007 Apr 10; 8:4. PMID: 17425781; PMCID: PMC1865377.
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Shi D, Caldovic L, Jin Z, Yu X, Qu Q, Roth L, Morizono H, Hathout Y, Allewell NM, Tuchman M. Expression, crystallization and preliminary crystallographic studies of a novel bifunctional N-acetylglutamate synthase/kinase from Xanthomonas campestris homologous to vertebrate N-acetylglutamate synthase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Dec 01; 62(Pt 12):1218-22. PMID: 17142901; PMCID: PMC2225375.
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Shi D, Yu X, Roth L, Morizono H, Tuchman M, Allewell NM. Structures of N-acetylornithine transcarbamoylase from Xanthomonas campestris complexed with substrates and substrate analogs imply mechanisms for substrate binding and catalysis. Proteins. 2006 Aug 01; 64(2):532-42. PMID: 16741992.
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Yamaguchi S, Brailey LL, Morizono H, Bale AE, Tuchman M. Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene. Hum Mutat. 2006 Jul; 27(7):626-32. PMID: 16786505.
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Shi D, Morizono H, Cabrera-Luque J, Yu X, Roth L, Malamy MH, Allewell NM, Tuchman M. Structure and catalytic mechanism of a novel N-succinyl-L-ornithine transcarbamylase in arginine biosynthesis of Bacteroides fragilis. J Biol Chem. 2006 Jul 21; 281(29):20623-31. PMID: 16704984.
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Moscioni D, Morizono H, McCarter RJ, Stern A, Cabrera-Luque J, Hoang A, Sanmiguel J, Wu D, Bell P, Gao GP, Raper SE, Wilson JM, Batshaw ML. Long-term correction of ammonia metabolism and prolonged survival in ornithine transcarbamylase-deficient mice following liver-directed treatment with adeno-associated viral vectors. Mol Ther. 2006 Jul; 14(1):25-33. PMID: 16677864.
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Morizono H, Cabrera-Luque J, Shi D, Gallegos R, Yamaguchi S, Yu X, Allewell NM, Malamy MH, Tuchman M. Acetylornithine transcarbamylase: a novel enzyme in arginine biosynthesis. J Bacteriol. 2006 Apr; 188(8):2974-82. PMID: 16585758; PMCID: PMC1446984.
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Caldovic L, Lopez GY, Haskins N, Panglao M, Shi D, Morizono H, Tuchman M. Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. Mol Genet Metab. 2006 Mar; 87(3):226-32. PMID: 16321554.
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Morizono H, Woolston JE, Colombini M, Tuchman M. The use of yeast mitochondria to study the properties of wild-type and mutant human mitochondrial ornithine transporter. Mol Genet Metab. 2005 Dec; 86(4):431-40. PMID: 16256388.
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Shi D, Yu X, Roth L, Morizono H, Hathout Y, Allewell NM, Tuchman M. Expression, purification, crystallization and preliminary X-ray crystallographic studies of a novel acetylcitrulline deacetylase from Xanthomonas campestris. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jul 01; 61(Pt 7):676-9. PMID: 16511126; PMCID: PMC1952451.
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Caldovic L, Morizono H, Panglao MG, Lopez GY, Shi D, Summar ML, Tuchman M. Late onset N-acetylglutamate synthase deficiency caused by hypomorphic alleles. Hum Mutat. 2005 Mar; 25(3):293-8. PMID: 15714518.
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Shi D, Morizono H, Yu X, Roth L, Caldovic L, Allewell NM, Malamy MH, Tuchman M. Crystal structure of N-acetylornithine transcarbamylase from Xanthomonas campestris: a novel enzyme in a new arginine biosynthetic pathway found in several eubacteria. J Biol Chem. 2005 Apr 15; 280(15):14366-9. PMID: 15731101.
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Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M. Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr. 2004 Oct; 145(4):552-4. PMID: 15480384.
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Morizono H, Caldovic L, Shi D, Tuchman M. Mammalian N-acetylglutamate synthase. Mol Genet Metab. 2004 Apr; 81 Suppl 1:S4-11. PMID: 15050968; PMCID: PMC3031861.
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Caldovic L, Morizono H, Panglao MG, Cheng SF, Packman S, Tuchman M. Null mutations in the N-acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia. Hum Genet. 2003 Apr; 112(4):364-8. PMID: 12594532.
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Caldovic L, Morizono H, Gracia Panglao M, Gallegos R, Yu X, Shi D, Malamy MH, Allewell NM, Tuchman M. Cloning and expression of the human N-acetylglutamate synthase gene. Biochem Biophys Res Commun. 2002 Dec 13; 299(4):581-6. PMID: 12459178.
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Shi D, Gallegos R, DePonte J, Morizono H, Yu X, Allewell NM, Malamy M, Tuchman M. Crystal structure of a transcarbamylase-like protein from the anaerobic bacterium Bacteroides fragilis at 2.0 A resolution. J Mol Biol. 2002 Jul 19; 320(4):899-908. PMID: 12095263.
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Caldovic L, Morizono H, Yu X, Thompson M, Shi D, Gallegos R, Allewell NM, Malamy MH, Tuchman M. Identification, cloning and expression of the mouse N-acetylglutamate synthase gene. Biochem J. 2002 Jun 15; 364(Pt 3):825-31. PMID: 12049647; PMCID: PMC1222632.
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Tuchman M, Jaleel N, Morizono H, Sheehy L, Lynch MG. Mutations and polymorphisms in the human ornithine transcarbamylase gene. Hum Mutat. 2002 Feb; 19(2):93-107. PMID: 11793468.
This graph shows the total number of publications by year, by first, middle/unknown, or last author.
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| Year | Publications |
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| 2002 | 4 | | 2003 | 1 | | 2004 | 2 | | 2005 | 4 | | 2006 | 7 | | 2007 | 3 | | 2008 | 4 | | 2009 | 2 | | 2010 | 1 | | 2011 | 2 | | 2012 | 1 | | 2014 | 1 | | 2015 | 1 | | 2016 | 1 | | 2017 | 1 |
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