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Neal Sondheimer

TitleStaff Physician
InstitutionThe Hospital for Sick Children
DepartmentClinical and Metabolic Genetics
Phone416-813-1500
ORCID ORCID Icon0000-0001-9982-5712 Additional info
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    Collapse Biography 
    Collapse education and training
    University of Chicago, Chicago, IL (USA)M.D.06/2002Medicine
    University of Chicago, Chicago, IL (USA)Ph.D.12/2000Molecular Genetics and Cell Biology

    Collapse Overview 
    Collapse overview
    Dr. Neal Sondheimer's research focuses on the regulation of mitochondrial gene expression and the impact of mitochondrial mutations in common and rare disease.

    -Strongly pathogenic mitochondrial sequence variants exist in a state of heteroplasmy, a mixture of normal and mutated genomes. This state provides opportunities for therapy, as the increase of wild type mitochondrial DNA or the suppression of mutated mitochondrial DNA could improve health. Sondheimer and his team are investigating mechanisms that could allow shifts in heteroplasmic ratios.

    -Dr. Sondheimer is interested in the effects of mitochondrial mutations in common diseases and phenotypes such as Alzheimer disease, aging and preterm birth. Because bioenergetic capacity is critical to many parts of the body, subtle changes in mitochondrial DNA may have profound effects over time.

    -The mitochondrial genome is the small, densely coding, matrilineally inherited DNA that encodes core subunits of the electron transport chain. Many features of gene regulation are more similar to bacterial and phage systems than they are to gene regulation in the nucleus. Defects in the maintenance of mitochondrial DNA and in the translation of gene products are known causes of disease. Sondheimer and his team are investigating the dysregulation of mitochondrial transcription as another possible avenue to bioenergetic failure.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Paik K, Lines MA, Chakraborty P, Khangura SD, Latocki M, Al-Hertani W, Brunel-Guitton C, Khan A, Penny B, Rockman-Greenberg C, Rupar CA, Sondheimer N, Tarnopolsky M, Tingley K, Coyle D, Dyack S, Feigenbaum A, Geraghty MT, Gillis J, van Karnebeek CDM, Kronick JB, Little J, Potter M, Siriwardena K, Sparkes R, Turner LA, Wilson K, Buhas D, Potter BK. Health Care for Mitochondrial Disorders in Canada: A Survey of Physicians. Can J Neurol Sci. 2019 Aug 07; 1-10. PMID: 31387656.
      View in: PubMed
    2. Naeem MM, Maheshan R, Costford SR, Wahedi A, Trajkovski M, Plavec J, Yatsunyk LA, Ciesielski GL, Kaufman BA, Sondheimer N. G-Quadruplex Mediated Reduction of a Pathogenic Mitochondrial Heteroplasmy. Hum Mol Genet. 2019 Jul 01. PMID: 31261379.
      View in: PubMed
    3. Coci EG, Gapsys V, Shur N, Shin-Podskarbi Y, de Groot BL, Miller K, Vockley J, Sondheimer N, Ganetzky R, Freisinger P. Pyruvate carboxylase deficiency type A and type C: Characterization of five novel pathogenic variants in PC and analysis of the genotype-phenotype correlation. Hum Mutat. 2019 Jun; 40(6):816-827. PMID: 30870574.
      View in: PubMed
    4. Naeem MM, Sondheimer N. Heteroplasmy Shifting as Therapy for Mitochondrial Disorders. Adv Exp Med Biol. 2019; 1158:257-267. PMID: 31452145.
      View in: PubMed
    5. Mellin-Sanchez L, Sondheimer N. An Infant Refugee with Anemia and Low Serum Vitamin B12. Clin Chem. 2018 11; 64(11):1567-1570. PMID: 30377178.
      View in: PubMed
    6. Veenma D, Cordeiro D, Sondheimer N, Mercimek-Andrews S. DNAJC12-associated developmental delay, movement disorder, and mild hyperphenylalaninemia identified by whole-exome sequencing re-analysis. Eur J Hum Genet. 2018 12; 26(12):1867-1870. PMID: 30139987.
      View in: PubMed
    7. Kaufman BA, Picard M, Sondheimer N. Mitochondrial DNA, nuclear context, and the risk for carcinogenesis. Environ Mol Mutagen. 2019 Jun; 60(5):455-462. PMID: 29332303.
      View in: PubMed
    8. Crawford N, Prendergast D, Oehlert JW, Shaw GM, Stevenson DK, Rappaport N, Sirota M, Tishkoff SA, Sondheimer N. Divergent Patterns of Mitochondrial and Nuclear Ancestry Are Associated with the Risk for Preterm Birth. J Pediatr. 2018 03; 194:40-46.e4. PMID: 29249523.
      View in: PubMed
    9. Sonney S, Leipzig J, Lott MT, Zhang S, Procaccio V, Wallace DC, Sondheimer N. Predicting the pathogenicity of novel variants in mitochondrial tRNA with MitoTIP. PLoS Comput Biol. 2017 12; 13(12):e1005867. PMID: 29227991.
      View in: PubMed
    10. Hogarth KA, Costford SR, Yoon G, Sondheimer N, Maynes JT. DNM1L Variant Alters Baseline Mitochondrial Function and Response to Stress in a Patient with Severe Neurological Dysfunction. Biochem Genet. 2018 Apr; 56(1-2):56-77. PMID: 29110115.
      View in: PubMed
    11. Zollo O, Sondheimer N. Topological requirements of the mitochondrial heavy-strand promoters. Transcription. 2017; 8(5):307-312. PMID: 28841355.
      View in: PubMed
    12. Lionel AC, Costain G, Monfared N, Walker S, Reuter MS, Hosseini SM, Thiruvahindrapuram B, Merico D, Jobling R, Nalpathamkalam T, Pellecchia G, Sung WWL, Wang Z, Bikangaga P, Boelman C, Carter MT, Cordeiro D, Cytrynbaum C, Dell SD, Dhir P, Dowling JJ, Heon E, Hewson S, Hiraki L, Inbar-Feigenberg M, Klatt R, Kronick J, Laxer RM, Licht C, MacDonald H, Mercimek-Andrews S, Mendoza-Londono R, Piscione T, Schneider R, Schulze A, Silverman E, Siriwardena K, Snead OC, Sondheimer N, Sutherland J, Vincent A, Wasserman JD, Weksberg R, Shuman C, Carew C, Szego MJ, Hayeems RZ, Basran R, Stavropoulos DJ, Ray PN, Bowdin S, Meyn MS, Cohn RD, Scherer SW, Marshall CR. Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. Genet Med. 2018 04; 20(4):435-443. PMID: 28771251.
      View in: PubMed
    13. Sondheimer N, Hewson S, Cameron JM, Somers GR, Broadbent JD, Ziosi M, Quinzii CM, Naini AB. Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency. Mol Genet Metab Rep. 2017 Sep; 12:23-27. PMID: 28540186.
      View in: PubMed
    14. Ahrens-Nicklas RC, Umanah GK, Sondheimer N, Deardorff MA, Wilkens AB, Conlin LK, Santani AB, Nesbitt A, Juulsola J, Ma E, Dawson TM, Dawson VL, Marsh ED. Precision therapy for a new disorder of AMPA receptor recycling due to mutations in ATAD1. Neurol Genet. 2017 Feb; 3(1):e130. PMID: 28180185.
      View in: PubMed
    15. Assoum M, Philippe C, Isidor B, Perrin L, Makrythanasis P, Sondheimer N, Paris C, Douglas J, Lesca G, Antonarakis S, Hamamy H, Jouan T, Duffourd Y, Auvin S, Saunier A, Begtrup A, Nowak C, Chatron N, Ville D, Mireskandari K, Milani P, Jonveaux P, Lemeur G, Milh M, Amamoto M, Kato M, Nakashima M, Miyake N, Matsumoto N, Masri A, Thauvin-Robinet C, Rivière JB, Faivre L, Thevenon J. Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy. Am J Hum Genet. 2016 Dec 01; 99(6):1368-1376. PMID: 27889060.
      View in: PubMed
    16. Seifert EL, Gál A, Acoba MG, Li Q, Anderson-Pullinger L, Golenár T, Moffat C, Sondheimer N, Claypool SM, Hajnóczky G. Natural and Induced Mitochondrial Phosphate Carrier Loss: DIFFERENTIAL DEPENDENCE OF MITOCHONDRIAL METABOLISM AND DYNAMICS AND CELL SURVIVAL ON THE EXTENT OF DEPLETION. J Biol Chem. 2016 Dec 09; 291(50):26126-26137. PMID: 27780865.
      View in: PubMed
    17. Seifert EL, Ligeti E, Mayr JA, Sondheimer N, Hajnóczky G. The mitochondrial phosphate carrier: Role in oxidative metabolism, calcium handling and mitochondrial disease. Biochem Biophys Res Commun. 2015 Aug 21; 464(2):369-75. PMID: 26091567.
      View in: PubMed
    18. Ganetzky R, Finn E, Bagchi A, Zollo O, Conlin L, Deardorff M, Harr M, Simpson MA, McGrath JA, Zackai E, Lemmon MA, Sondheimer N. EGFR mutations cause a lethal syndrome of epithelial dysfunction with progeroid features. Mol Genet Genomic Med. 2015 Sep; 3(5):452-8. PMID: 26436111.
      View in: PubMed
    19. Sondheimer N, Soundararajan S, Koutzaki SH, Doyle AM. Kidney transplantation from a deceased donor with metachromatic leukodystrophy. Transplantation. 2014 Apr 15; 97(7):e42-4. PMID: 24686430.
      View in: PubMed
    20. Sondheimer N, Zollo O, Van Deerlin V, Trojanowski JQ. Analysis of cerebrospinal fluid mitochondrial DNA levels in Alzheimer disease. Ann Neurol. 2014 Mar; 75(3):458-60. PMID: 24424574.
      View in: PubMed
    21. Gai X, Ghezzi D, Johnson MA, Biagosch CA, Shamseldin HE, Haack TB, Reyes A, Tsukikawa M, Sheldon CA, Srinivasan S, Gorza M, Kremer LS, Wieland T, Strom TM, Polyak E, Place E, Consugar M, Ostrovsky J, Vidoni S, Robinson AJ, Wong LJ, Sondheimer N, Salih MA, Al-Jishi E, Raab CP, Bean C, Furlan F, Parini R, Lamperti C, Mayr JA, Konstantopoulou V, Huemer M, Pierce EA, Meitinger T, Freisinger P, Sperl W, Prokisch H, Alkuraya FS, Falk MJ, Zeviani M. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy. Am J Hum Genet. 2013 Sep 05; 93(3):482-95. PMID: 23993194.
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    22. Clarke C, Xiao R, Place E, Zhang Z, Sondheimer N, Bennett M, Yudkoff M, Falk MJ. Mitochondrial respiratory chain disease discrimination by retrospective cohort analysis of blood metabolites. Mol Genet Metab. 2013 Sep-Oct; 110(1-2):145-52. PMID: 23920046.
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    23. Vergano SA, Crossette JM, Cusick FC, Desai BR, Deardorff MA, Sondheimer N. Improving surveillance for hyperammonemia in the newborn. Mol Genet Metab. 2013 Sep-Oct; 110(1-2):102-5. PMID: 23746553.
      View in: PubMed
    24. Sondheimer N. Newborn screening by sequence and the road ahead. Clin Chem. 2013 Jul; 59(7):1011-3. PMID: 23529705.
      View in: PubMed
    25. Spinale JM, Laskin BL, Sondheimer N, Swartz SJ, Goldstein SL. High-dose continuous renal replacement therapy for neonatal hyperammonemia. Pediatr Nephrol. 2013 Jun; 28(6):983-6. PMID: 23471476.
      View in: PubMed
    26. D'Aco KE, Manno M, Clarke C, Ganesh J, Meyers KE, Sondheimer N. Mitochondrial tRNA(Phe) mutation as a cause of end-stage renal disease in childhood. Pediatr Nephrol. 2013 Mar; 28(3):515-9. PMID: 23135609.
      View in: PubMed
    27. Schadt EE, Banerjee O, Fang G, Feng Z, Wong WH, Zhang X, Kislyuk A, Clark TA, Luong K, Keren-Paz A, Chess A, Kumar V, Chen-Plotkin A, Sondheimer N, Korlach J, Kasarskis A. Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases. Genome Res. 2013 Jan; 23(1):129-41. PMID: 23093720.
      View in: PubMed
    28. Zollo O, Tiranti V, Sondheimer N. Transcriptional requirements of the distal heavy-strand promoter of mtDNA. Proc Natl Acad Sci U S A. 2012 Apr 24; 109(17):6508-12. PMID: 22454497.
      View in: PubMed
    29. Grant SF, Glessner JT, Bradfield JP, Zhao J, Tirone JE, Berkowitz RI, Hakonarson H, Sondheimer N. Lack of relationship between mitochondrial heteroplasmy or variation and childhood obesity. Int J Obes (Lond). 2012 Jan; 36(1):80-3. PMID: 22005716.
      View in: PubMed
    30. Glatz C, D'Aco K, Smith S, Sondheimer N. Mutation in the mitochondrial tRNA(Val) causes mitochondrial encephalopathy, lactic acidosis and stroke-like episodes. Mitochondrion. 2011 Jul; 11(4):615-9. PMID: 21540128.
      View in: PubMed
    31. Sondheimer N, Glatz CE, Tirone JE, Deardorff MA, Krieger AM, Hakonarson H. Neutral mitochondrial heteroplasmy and the influence of aging. Hum Mol Genet. 2011 Apr 15; 20(8):1653-9. PMID: 21296868.
      View in: PubMed
    32. Falk MJ, Sondheimer N. Mitochondrial genetic diseases. Curr Opin Pediatr. 2010 Dec; 22(6):711-6. PMID: 21045694.
      View in: PubMed
    33. Sondheimer N, Fang JK, Polyak E, Falk MJ, Avadhani NG. Leucine-rich pentatricopeptide-repeat containing protein regulates mitochondrial transcription. Biochemistry. 2010 Sep 07; 49(35):7467-73. PMID: 20677761.
      View in: PubMed
    34. Guha M, Tang W, Sondheimer N, Avadhani NG. Role of calcineurin, hnRNPA2 and Akt in mitochondrial respiratory stress-mediated transcription activation of nuclear gene targets. Biochim Biophys Acta. 2010 Jun-Jul; 1797(6-7):1055-65. PMID: 20153290.
      View in: PubMed
    35. Chapman KA, Bennett MJ, Sondheimer N. Increased C3-carnitine in a healthy premature infant. Clin Chem. 2008 Nov; 54(11):1914-7; discussion 1917-8. PMID: 18957557.
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    36. Deardorff MA, Gaddipati H, Kaplan P, Sanchez-Lara PA, Sondheimer N, Spinner NB, Hakonarson H, Ficicioglu C, Ganesh J, Markello T, Loechelt B, Zand DJ, Yudkoff M, Lichter-Konecki U. Complex management of a patient with a contiguous Xp11.4 gene deletion involving ornithine transcarbamylase: a role for detailed molecular analysis in complex presentations of classical diseases. Mol Genet Metab. 2008 Aug; 94(4):498-502. PMID: 18524659.
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    37. Biswas G, Tang W, Sondheimer N, Guha M, Bansal S, Avadhani NG. A distinctive physiological role for IkappaBbeta in the propagation of mitochondrial respiratory stress signaling. J Biol Chem. 2008 May 02; 283(18):12586-94. PMID: 18272519.
      View in: PubMed
    38. Ernst LM, Sondheimer N, Deardorff MA, Bennett MJ, Pawel BR. The value of the metabolic autopsy in the pediatric hospital setting. J Pediatr. 2006 Jun; 148(6):779-83. PMID: 16769386.
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    39. Liu JJ, Sondheimer N, Lindquist SL. Changes in the middle region of Sup35 profoundly alter the nature of epigenetic inheritance for the yeast prion [PSI+]. Proc Natl Acad Sci U S A. 2002 Dec 10; 99 Suppl 4:16446-53. PMID: 12461168.
      View in: PubMed
    40. Sondheimer N, Lopez N, Craig EA, Lindquist S. The role of Sis1 in the maintenance of the [RNQ+] prion. EMBO J. 2001 May 15; 20(10):2435-42. PMID: 11350932.
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    41. Lindquist S, Krobitsch S, Li L, Sondheimer N. Investigating protein conformation-based inheritance and disease in yeast. Philos Trans R Soc Lond B Biol Sci. 2001 Feb 28; 356(1406):169-76. PMID: 11260797.
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    42. Satyal SH, Schmidt E, Kitagawa K, Sondheimer N, Lindquist S, Kramer JM, Morimoto RI. Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2000 May 23; 97(11):5750-5. PMID: 10811890.
      View in: PubMed
    43. Sondheimer N, Lindquist S. Rnq1: an epigenetic modifier of protein function in yeast. Mol Cell. 2000 Jan; 5(1):163-72. PMID: 10678178.
      View in: PubMed
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