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About Sickkids
About SickKids

Neal Sondheimer, MD, PhD

The Hospital for Sick Children
Staff Physician
Clinical and Metabolic Genetics

Research Institute
Associate Scientist
Genetics & Genome Biology

University of Toronto
Assistant Professor
Department of Paediatrics

Phone: 416-813-7654 x 201480
Email: neal.sondheimer@sickkids.ca

Brief Biography

  • MD/PhD – The University of Chicago (thesis work with Susan Lindquist)
  • Clinical Training in Paediatrics, Genetics and Clinical Biochemistry – The Children’s Hospital of Philadelphia

Research Interests

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 mutations 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.
  • 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.

External Funding

  • The March of Dimes


Ganetzky R, Finn E, Bagchi A, Zollo O, Conlin L, Deardorff M, Harr M, Simpson M, McGrath J, Zackai E, Lemmon M, Sondheimer N (2015) EGFR mutations cause a lethal syndrome of epithelial dysfunction with progeroid features. Mol. Genet. Genomic Med. 3, 452-458.

Sondheimer N, Zollo O, Van Deerlin V, Trojanowski JQ (2014) Analysis of cerebrospinal fluid mitochondrial DNA levels in Alzheimer disease. Ann. Neurol. 75, 458–460.

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 (2013) Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases. Genome Res. 23, 129–141.

D’Aco KE, Manno M, Clarke C, Ganesh J, Meyers KEC, Sondheimer N (2013) Mitochondrial tRNA(Phe) mutation as a cause of end-stage renal disease in childhood. Pediatr. Nephrol. 28, 515–519.

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 L-J, 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 (2013) Mutations in FBXL4, Encoding a Mitochondrial Protein, Cause Early-Onset Mitochondrial Encephalomyopathy. Am. J. Hum. Genet. 93, 482-495.

Vergano SA, Crossette JM, Cusick FC, Desai BR, Deardorff MA, Sondheimer N (2013) Improving surveillance for hyperammonemia in the newborn. Mol. Genet. Metab. 110, 102–105.

Grant SFA, Glessner JT, Bradfield JP, Zhao J, Tirone JE, Berkowitz RI, Hakonarson H, Sondheimer N (2012) Lack of relationship between mitochondrial heteroplasmy or variation and childhood obesity. Int. J. Obes. (Lond). 36, 80–83.

Zollo O, Tiranti V, Sondheimer N (2012) Transcriptional requirements of the distal heavy-strand promoter of mtDNA. Proc. Natl. Acad. Sci. U. S. A. 109, 6508–6512.

Glatz C, D’Aco K, Smith S, Sondheimer N (2011) Mutation in the mitochondrial tRNA(Val) causes mitochondrial encephalopathy, lactic acidosis and stroke-like episodes. Mitochondrion 11, 615–619.

Sondheimer N, Glatz CE, Tirone JE, Deardorff MA, Krieger AM, Hakonarson H (2011) Neutral mitochondrial heteroplasmy and the influence of aging. Hum. Mol. Genet. 20, 1653–1659.

Falk MJ, Sondheimer N (2010) Mitochondrial genetic diseases. Curr. Opin. Pediatr. 22, 711–716.