Neal Sondheimer

Medical Director, Phenylketonuria Program, Division of Clinical and Metabolic Genetics

Staff Physician, Division of Clinical and Metabolic Genetics

Senior Associate Scientist, Genetics & Genome Biology

Dr. Neal Sondheimer completed his MD and PhD in Molecular Genetics at The University of Chicago. He completed his residencies in paediatrics, medical genetics and metabolics at The Children’s Hospital of Philadelphia. Since coming to The Hospital for Sick Children (SickKids) in 2015, he has provided care for children with metabolic diseases including phenylketonuria and mitochondrial disorders.

Research

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

• Strong 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. Dr. 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, autism 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, maternally 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. Dr. Sondheimer and his team are investigating the dysregulation of mitochondrial transcription as another possible avenue to bioenergetic failure.

Education

• 1990–1994: Bachelor of Arts (AB), Biology, Harvard University, Cambridge, Massachusetts, United States.
• 1995–2000: Doctor of Philosophy (PhD), Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois, United States.
• 1995–2002: Doctor of Medicine (MD), University of Chicago, Pritzker School of Medicine, Chicago, Illinois, United States.

Experience

• 2006–2015: Attending Physician, Biochemical Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.
• 2007–2009: Clinical Associate in Pediatrics, Department of Paediatrics, The University of Pennsylvania, Philadelphia, Pennsylvania, United States.
• 2008–2012: Co-Director, Mitochondrial Research Affinity Group, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.
• 2009–2015: Assistant Professor of Pediatrics (Tenure track), Department of Paediatrics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, United States.
• 2014–2015: Training Director, Clinical Biochemical Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.
• 2014–2015: Program Director, The Children’s Hospital of Philadelphia and Medical Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
• 2015–2018: Assistant Professor, Department of Paediatrics, University of Toronto, Toronto, Ontario.
• 2016–2018: Associate Member, Institute of Medical Sciences, University of Toronto, Toronto, Ontario.
• 2017: Interim Program Director, Postgraduate Medical Education, Department of Paediatrics, University of Toronto, Toronto, Ontario.
• 2018: Assistant Professor Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario.
• 2018: Adjunct Professor, Joint Institute of Genetics and Genome Medicine Genetics, School of Medicine, Zhejiang University, China.

Achievements

• 2016: Faculty, North American Metabolic Academy.
• 2013: Young Physician-Scientist Award, American Society for Clinical Investigation.
• 2012: Society for Pediatric Research, The Woodlands, Honorary Society.

1. Djordjevic D, Tsuchiya E, Fitzpatrick M, Sondheimer N, Dowling JJ. (2020) Utility of metabolic screening in neurological presentations of infancy. Ann Clin Transl Neurol. Jul; 7(7):1132-1140. 
2. Mishmar D, Levin R, Naeem MM, Sondheimer N. Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A. (2019) Front Genet.; 10:1285.
3. 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. (2019) Hum Mol Genet. 10 01; 28(19):3163-3174.
4. Crawford N, Prendergast D, Oehlert JW, Shaw GM, Stevenson DK, Rappaport N, Sirota M, Tishkoff SA, Sondheimer N. (2018). Divergent patterns of mitochondrial and nuclear ancestry are associated with the risk for preterm birth. Journal of Pediatrics. 194: 40-46.
5. Sonney S, Leipzig J, Lott MT, Zhang S, Procaccio V, Wallace DC, Sondheimer N. (2017). Predicting the pathogenicity of novel variants in mitochondrial tRNA with MitoTIP. PLOS Computational Biology, 13, e1005867.

External funding

• 2020–2024: Mitochondrial G-quadruplex structures in health and disease, Co-Investigator, National Institutes of Health/National Institute of General Medical Sciences (Subcontract). 
• 2018–2023: The role of mitochondrial dysfunction in neurotransmission: Implications for bipolar disorder, Co-Investigator, Canadian Institutes of Health Research. 
• 2018–2020: Transgenerational Mitochondrial Mutations in Autism, Principal Investigator, Simons Foundation Autism Research Initiative. 
• 2014–2020: Transdisciplinary Research Center for Preterm Birth, Co-Investigator, March of Dimes Foundation, March of Dimes Center for Prematurity Research at the University of Pennsylvania.