Facebook Pixel Code
About Sickkids
About SickKids

Ingrid Tein, MD, FRCP(C)

The Hospital for Sick Children
Staff Neurologist
Neurology

Research Institute
Senior Associate Scientist
Genetics & Genome Biology

University of Toronto
Associate Professor
Paediatrics


Phone: 416-813-5668
Fax: 416-813-6334
Email: ingrid.tein@sickkids.ca

Brief Biography

Dr. Tein obtained her B.S.c and MD from the University of Toronto. She completed her paediatric and paediatric neurology training at The Hospital for Sick Children (SickKids) in Toronto. She then did her post-doctoral research training in fatty acid oxidation disorders at Hôpital Necker-Enfants Malades, Faculté de Médécine in Paris with Professor J.M. Saudubray in 1987 and in the Department of Neurology at Columbia University in New York with Dr. Darryl DeVivo and Dr. Salvatore DiMauro from 1988 to 1990.

In 1991, Dr. Tein returned to SickKids  as a Staff Neurologist in the Division of Neurology and founded the Neurometabolic Clinic, the Neuroinvestigational Unit and the Neurometabolic Research Laboratory. She was recipient of the Samuel Lunenfeld Foundation Scholarship in 1991 and the Medical Research Council of Canada Scholarship in 1992. Dr. Tein is an Associate Professor of Paediatrics, Laboratory Medicine and Pathobiology at the University of Toronto and was promoted to Senior Scientist in the SickKids Research Institute in 2003.

Dr. Tein directs the Neurometabolic Clinic and maintains an active clinical practice in the investigation and treatment of children with neurometabolic diseases including mitochondrial, fatty acid oxidation, glycolytic and peroxisomal disorders, while continuing her laboratory research. The Neuroinvestigational Unit includes prospective multidisciplinary cross-over cofactor trials in children with mitochondrial disorders and the ergometric investigation of metabolic myopathies. The goal of the research laboratory is the biochemical and molecular investigation of genetic fatty acid oxidation defects and development of in vitro disease models to understand pathophysiological mechanisms. She has identified novel clinical and biochemical phenotypes and genotypes, developed new diagnostic screening tests now incorporated into NIH metabolic protocols, and developed novel treatment strategies aimed at bypassing or correcting the specific metabolic block which have decreased long-term morbidity and mortality and have been successfully implemented internationally. Her research has been supported by the MRC, CIHR, Heart and Stroke Foundation, PSI Foundation and UMDF. Dr. Tien has served as the Director of the Adam Barsky Lectureship in Mitochondrial Diseases since 1995 and the Sarah Langer Mitochondrial Studentships since 2000 and she founded the Neurometabolic Fellowship program in 2007.

Dr. Tein was recipient of the ICNA John Stobo Prichard Young Investigator Award in 1998 and the Detweiler Fellowship from the Royal College of Physicians and Surgeons of Canada in 2004. She has served on the International SCAD Consortium since 1997, on multiple North American Clinical and Research Advisory Boards (NIH, MDAC, MRC, CIHR, SMA) and on the Editorial Boards of Pediatric Neurology and Brain and Development. She has given over 200 invited talks, 90 internationally. Dr. Tein is an elected member of the Executive Board of the International Child Neurology Association for the promotion of excellence in clinical care, education and research in Child Neurology internationally. She served as Chair of the Scientific Program Committee for the XIth International Child Neurology Congress in Cairo, 2010 and serves on the Research Task Force and Editorial Board of the International Review of Child Neurology Book Series.

Academic Background

Duncan L. Gordon Fellowship
The Hospital for Sick Children Foundation

Fellow, Von Aitken Coma Foundation Trust
Columbia University, NY

American Muscular Dystrophy Association for Neuromuscular Diseases Research Fellowship
Columbia University, NY

Research Interests

  • Organic Cation/Carnitine Transporter Family
  • Fatty Acid Oxidation
  • Mitochondrial Metabolism and Diseases
  • Metabolic Myopathies and Exercise IntoleranceFatty Acid Oxidation
  • Molecular Genetics

Research Activities

A) Fatty acid oxidation:

  1. The primary focus of our research program is the biochemical and molecular characterization of the organic cation/carnitine transporter family OCTN1, OCTN2 and OCTN3 and to increase understanding of their regulation and roles in maintaining intracellular carnitine homeostasis in brain, heart, muscle, testis and developing mammary gland. We discovered a new human carnitine transporter, OCTN3, using functional cloning and proteomic technologies. Our functional characterization of the OCTN3 protein indicated that it is a candidate susceptibility gene for Crohn’s disease at 5q31. We further demonstrated the novel localization of OCTN1 to mitochondria and of OCTN3 to peroxisomes. We are investigating the roles of OCTN1 and OCTN3 in neurological (cerebral bioenergetics, cholinergic neurotransmission) and inflammatory bowel diseases (epitopic mimicry). We also identified the first as well as a large series of novel mutations in the OCTN2 gene and could find no genotype-phenotype correlations, suggesting that the wide phenotypic variability is likely multifactorial and influenced by exogenous stressors.
  2. Our secondary focus is the clinical, biochemical and molecular characterization of genetic defects in fatty acid oxidation resulting in recurrent encephalopathy, myoglobinuria and/or lipid storage myopathy and cardiomyopathy including carnitine palmitoyltransferase I and II, short-chain acyl-CoA dehydrogenase (SCAD), and short- and long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiencies. We have identified new diseases, novel phenotypes and genotypes and developed new diagnostic screening tests.
  3. Our third focus is the development of in vitro cellular models to study the pathophysiologic mechanisms of fatty acid-associated cellular toxicity in different genetic disorders of fatty acid oxidation for the development of novel treatment strategies to circumvent or correct the specific metabolic block(s) and/or decrease the toxicity of accumulated metabolites. We have successfully translated these findings to the bedside which in the aggregate have significantly decreased long-term morbidity in affected individuals (e.g. oxidative stress/protein misfolding in SCAD deficiency, membranotoxicity in trifunctional protein deficiency) and have been implemented internationally.

B) Mitochondrial disorders:

  1. We conduct prospective multidisciplinary (neurological, neurophysiological, biochemical, ergometric, quality of life) cross-over clinical trials to assess the efficacy of cofactor and antioxidant treatments which we have targeted to the site of dysfunction in different mitochondrial disorders. We are investigating the mechanism(s) of action of L-arginine on endothelium-dependent vasodilation and mitochondrial metabolism in MELAS syndrome using 31P-MRS cycle ergometry and BOLD-fMRI studies of cerebrovascular reactivity.

C) Exercise intolerance

  1. We investigate the mechanisms of exercise intolerance in chronic  childhood diseases, including metabolic myopathies and cystic fibrosis, using exercise physiology, 31P-MR spectroscopy, and ultrastructural, biochemical and molecular tools. We have demonstrated the expression of CFTR in human skeletal muscle and it's dysfunction in CFTR ΔF508 -/- murine muscle which correlate with significant metabolic abnormalities in the exercising muscle of CF patients as demonstrated by 31P-MRS.

Future Research Interests

Development of Paediatric Metabolic Exercise Physiology Unit

External Funding

  • CIHR
  • Heart and Stroke Foundation
  • Physicians' Services Incorporated Foundation United Mitochondrial Diseases Foundation Mead Johnson

Achievements

1/87-12/89 - Duncan L. Gordon Research Fellowship, SickKids Foundation, The Hospital for Sick Children, Toronto

7/89-12/90 - Von Aitken Coma Foundation Trust Research Fellowship, Columbia University, New York, New York

1/90-12/90 - American Muscular Dystrophy Association Neuromuscular Diseases Research, Fellowship (held at Columbia University, NY, NY)

1/91-12/93 - S.Lunenfeld Foundation Scholarship, The Hospital for Sick Children, Toronto 

7/92-6/97 - Medical Research Council of Canada Scholarship 

6/93 - Selected by Medical Research Council of Canada to represent Canada at Lindau meeting of Nobel Laureates, Lindau, Germany

7/92-6/93 - William A. Hawke Award, Clinical Excellence in Teaching, Division of Neurology Neurology, The Hospital for Sick Children, Toronto, Ontario

9/94-8/95 - Appointment to Dean's Research Advisory Committee, University of Toronto

9/98 - John Stobo Prichard Award - Young Investigator Award,  8th International Child Neurology Association Congress, Ljubljana, Slovenia 

5/02 - Young Investigator Scholarship, Pediatric Neurotransmitter Symposium, NIH, Washington, DC. May 17-19, 2002

10/03-09/04 - Detweiler Travelling Scholarship, Awarded by the Royal College of Physicians and Surgeons of Canada

11/07 Teaching Award, Hong Kong Society of Child Neurology and Developmental Pediatrics, University of Hong Kong

7/07-6/08 Pediatric Subspecialty Teaching Award. Dept. Pediatrics, The Hospital for Sick Children (2nd place), University of Toronto

7/08-6/09 William A. Hawke Award, Clinical Excellence in Teaching, Division of Neurology, The Hospital for Sick Children, University of Toronto,  

Publications

 Lamhonwah AM,  Bear CE, Huan LJ, Ackerley C, Tein I. CFTR in Human Muscle. Dysfunction Causes Abnormal Metabolic Recovery in Exercise. Annals of Neurology. 2010; 67:802-806

Wells GD, Wilkes DL, Schneiderman-Walker J, Rayner T, Elmi M, Selvaduria H, Ratjen F, Noseworthy M, Tein I, Coates A. Skeletal Muscle Metabolism in Cystic Fibrosis and Primary Ciliary Dyskinesia. Pediatric Research 2011; 69: 40-45

Lamhonwah AM, Mai L, Chung C, Lamhonwah D, Ackerley C, Tein I. Upregulation of mammary gland OCTNs maintains carnitine homeostasis in suckling infants. Biochem Biophys Res Commun. 2011; 404: 1010-1015

Tein I, Elpeleg O., BenZe’ev B, Korman S, Lossos A, Lev D, Lerman-Sagie T, Leshinsky-Silver E, Vockley G, Berry G, Lamhonwah AM, Matern D, Roe C, Gregersen N. Short-chain acyl-CoA dehydrogenase gene mutation (c.319 C>T) presents with clinical heterogeneity and is candidate founder mutation in individuals of Ashkenazi Jewish origin. Molecular Genetics and Metabolism. 2008;93:179-189

Lamhonwah AM, Hawkins C, Tam C, Wong J, Mai L, Tein I. Expression patterns of organic cation/carnitine transporter family in adult murine brain. Brain and Development. 2008; 30: 31-42

Lamhonwah AM, Tein I. Novel localization of OCTN1, an Organic Cation/Carnitine Transporter, to Mammalian Mitochondria. Biochem Biophys Res Commun 2006; 345:1315-1325

Lamhonwah AM, Ackerley C, Onizuka R, Tilups A, Lamhonwah D, Chung C, Tao KS, Tellier R, Tein I. Epitope shared by functional variant of organic cation/carnitine transporter, OCTN1, Campylobacter jejuni and Mycobacterium paratuberculosis may underlie susceptibility to Crohn’s disease at 5q31. Biochem Biophys Res Commun 2005; 337:1165-1175  

Lamhonwah AM, Skaug, J, Scherer SW, Tein I. A third human carnitine/organic cation transporter (OCTN3) as a candidate for the 5q31 Crohn’s disease locus (IBD5).  Biochem Biophys Res Commun  2003; 301: 98-101

Lamhonwah AM, Olpin SE, Pollitt RJ, Vianey-Saban C, Divry P, Guffon N, Besley  GTN, Onizuka R, De Meirleir LJ, Cvitanovic-Sojat L, Baric I, Dionisi-Vici  C, Fumic K, Maradin M, Tein I.  Novel OCTN2 Mutations: No Genotype-Phenotype Correlations. Early Carnitine Therapy Prevents Cardiomyopathy.  Am J Med Genet  2002; 111: 271-284  

Ibdah JA, Tein I, Dionisi-Vici C, Bennett MJ, Ijlst L, Gibson B, Wanders RJ, Strauss AW. Mild TFP deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation. J Clin Invest 1998; 102:1193-1199