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About Sickkids
About SickKids

Neal Sondheimer, MD, PhD

The Hospital for Sick Children
Interim Division Head
Clinical and Metabolic Genetics

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 228780
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.
  • 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.

External Funding

  • The March of Dimes


Mitochondrial DNA, nuclear context, and the risk for carcinogenesis. Kaufman BA, Picard M, Sondheimer N. Environ Mol Mutagen. 2018. in press.

Divergent Patterns of Mitochondrial and Nuclear Ancestry Are Associated with the Risk for Preterm Birth. Crawford N, Prendergast D, Oehlert JW, Shaw GM, Stevenson DK, Rappaport N, Sirota M, Tishkoff SA, Sondheimer N. J Pediatr. 2018. 194:40-46

Predicting the pathogenicity of novel variants in mitochondrial tRNA with MitoTIP. Sonney S, Leipzig J, Lott MT, Zhang S, Procaccio V, Wallace DC, Sondheimer N. PLoS Comput Biol. 2017 Dec 11;13(12):e1005867.

DNM1L Variant Alters Baseline Mitochondrial Function and Response to Stress in a Patient with Severe Neurological Dysfunction. Hogarth KA, Costford SR, Yoon G, Sondheimer N, Maynes JT. Biochem Genet. 2018 Apr;56(1-2):56-77.

Red Blood Cells Homeostatically Bind Mitochondrial DNA through TLR9 to Maintain Quiescence and to Prevent Lung Injury. Hotz MJ, Qing D, Shashaty MGS, Zhang P, Faust H, Sondheimer N, Rivella S, Worthen GS, Mangalmurti NS. Am J Respir Crit Care Med. 2018 Feb 15;197(4):470-480.

Topological requirements of the mitochondrial heavy-strand promoters. Zollo O, Sondheimer N. Transcription. 2017;8(5):307-312

Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency Sondheimer N, Hewson S, Cameron JM, Somers GR, Broadbent JD, Ziosi M, Quinzii CM, Naini AB. Mol Genet Metab Rep. 2017 May 11;12:23-27

Precision therapy for a new disorder of AMPA receptor recycling due to mutations in ATAD1. 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. Neurol Genet. 2017 Feb 1;3(1):e130.

Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy. 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. Am J Hum Genet. 2016 Dec 1;99(6):1368-1376.