University of Cincinnati Department of Pediatrics

Arnold Strauss, MD, is the head of the Cincinnati Children's Research Foundation and the Chair of the Department of Pediatrics at the University of Cincinnati College of Medicine

Arnold W. Strauss, MD

Title

BK Rachford Professor and Chair, Department of Pediatrics, University of Cincinnati College of Medicine; Director, Cincinnati Children's Research Foundation; Chief Medical Officer, Cincinnati Children's Hospital Medical Center

Appointment

Professor of Pediatrics

Email

arnold.strauss@cchmc.org

Phone

513-636-2942

Bio

Arnold Strauss, MD, joined Cincinnati Children's in April, 2007, as chairman of the Department of Pediatrics at the UC College of Medicine, chief medical officer of Cincinnati Children's and director of the Cincinnati Children's Research Foundation. He is the seventh B.K. Rachford Memorial Chair in Pediatrics.

Dr. Strauss is a distinguished pediatric cardiologist, scientist, educator and leader. Prior to his arrival at Cincinnati Children's, he was the chairman of the Department of Pediatrics at the Vanderbilt University School of Medicine and medical director of the Monroe Carell Jr. Children's Hospital at Vanderbilt, a position he held from 2000 to 2007. Under his leadership, the university built and opened a new hospital for children, expanded its pediatric faculty and increased grant funding for pediatric research. From 1981 to 2000, Strauss was director of the Division of Pediatric Cardiology at Washington University/St. Louis Children's Hospital.

A respected scientist, Dr. Strauss' research focuses on understanding the molecular basis of disorders of mitochondrial fatty acid oxidation and the genetic causes of congenital heart disease and cardiomyopathies. He is the recipient of two of the most prestigious awards in research. In November 2006 he was awarded the American Heart Association's Basic Science Research Award for groundbreaking work that led to finding genetic defects that can cause heart failure and sudden death in infants and children. In 1991 he received the E. Mead Johnson Award for Excellence in Pediatric Research.

Credentials

MD Washington University, St. Louis, Missouri, 1970
Residency Pediatrics, Children's Hospital, St. Louis, Missouri, 1970-72
Fellowship Cardiology, Children's Hospital and Washington University, St. Louis, Missouri, 1972-75
Postdoctoral Fellowship Merck, Sharp and Dohme Research Laboratories, Rahway, New Jersey, 1975-77

Position History

2000-2007 Professor of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee
2000-2007 James C. Overall Professor and Chair, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
2001-2007 Investigator, Program in Human Genetics, Vanderbilt University School of Medicine, Nashville, Tennessee
2000-2007 Kennedy Center for Research in Human Development, Investigator, Vanderbilt University School of Medicine, Nashville, Tennessee
2000-2007 Adjunct Professor of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
1998-2000 Alumni Endowed Professor of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
1992-2000 Professor of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri
1989-1992 Professor of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri
1983-1989 Professor of Biological Chemistry, Washington University, St. Louis, Missouri
1982-1998 Professor of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
1981-2000 Director, Division of Pediatric Cardiology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri
1980-1982 Associate Professor of Biological Chemistry, Washington University, St. Louis, Missouri
1979-1982 Associate Professor of Pediatrics, Washington University, St. Louis, Missouri
1977-1980 Assistant Professor of Biological Chemistry, Washington University, St. Louis, Missouri
1977-1979 Assistant Professor of Pediatrics, Washington University, St. Louis, Missouri

Awards and Honors

Phi Beta Kappa, 1966
Alpha Omega Alpha, 1970
Established Investigator of the American Heart Association, 1979-1984
E. Mead Johnson Award for Excellence in Pediatric Research, 1991
NIH Grant AM 20407, Principal Investigator, 1977-1999
MERIT status, 1991-1999
Listed in "Best Doctors in America", 1994-2006
Alumni Faculty Award, Washington University, 1995
Basic Science Award, American Heart Association, 2006
Best Doctors in America, 2008

Research

My laboratory focuses on energy generation by mitochondria through fatty acid oxidation (FAO). Highly oxidative tissues such as heart, skeletal muscle, gut, and kidney rely upon FAO for energy and intermediary metabolism of fatty acids in the liver is the major source of short chain fatty acids, "ketone bodies" that are important fuels in the brain. The fetal-maternal metabolic transition is a switch from glucose to fatty acids as the major energy source. My laboratory has cloned and characterized mouse and human genes encoding five enzymes of the FAO pathway-medium chain acyl-CoA dehydrogenase (MCAD), very long chain acyl-CoA dehydrogenase (VLCAD), the two genes of the trifunctional protein (TFP) subunits, and medium and short chain 3-hydroxy-acyl-CoA dehydrogenase (SCHAD). We study the molecular genetics of infants and children with mutations in these genes causing sudden infant death syndrome, Reye's syndrome (hypoketotic hypoglycemia and acute liver failure), cardiomyopathy, and recurrent skeletal myopathy. Because newborn screening now detects these disorders, we are studying the specificity and sensitivity of this approach, and we are defining many intriguing mutations in all of these genes in asymptomatic newborns picked up by tandem mass spectroscopy analyses. These data demonrstrate that fatty acid oxidation defects occur in about 1/4,000 newborns and that subsequent death and morbidity can be prevented.

We continue to define the relationship between fetal FAO defects and the development of severe maternal liver diseases, including acute fatty liver of pregnancy and the HELLP syndrome. Using overexpression systems, x-ray crystallography, and biochemical analyses, structure-function relationships of normal and mutant enzymes are explored. Through transgenic mice and in vitro transfection experiments, transcriptional regulation is being examined for all of these genes.

Using gene ablation techniques, mice with deficiency of all five genes have been created that exhibit the phenotypes of sudden death in infancy, death following exposure to fasting and the cold, late-onset obesity, cardiac arrhythmias, and late-onset abdominal tumors. Microarray and proteomic analyses are being conducted to understand adaptation of these knock-out animals and the mechanisms of arrhythmogenesis and tumorigenesis.

We have initiated a project on the genetic basis of Barth's syndrome, an X-linked disorder characterized by cardiomyopathy, skeletal myopathy, cyclic neutropenia, and premature death in affected boys that is caused by mutations in tafazzin, a mitochondrial phospholipid transferase, and results in deficiency of cardiolipin, a unique tetra-acyl phospholipid present only in mitochondria. We have generated zebrafish and mouse models of this disorder that share the human phenotype in order to examine the pathogenesis and adaptation.

Research Grants and Contracts

Adaptation to Long Chain Fatty Acid Oxidation Deficiency: 1R01HL075421, Active | 04/01/04-03/31/08 | NHLBI | Principal Investigator
The goals of this project are to examine genotype-phenotype correlations and the pathogenetics of very-long-chain acyl-CoA dehydrogenase deficiency in humans, to characterize a mouse model of VLCAD deficiency, to create and analyze tissue-specific VLCAD knockouts, and to define the role of heart endothelin related substance in adaptation in the VLCAD knockout mouse. These studies utilize many of the techniques of the current application, including proteomics and DNA microarray experiments. Drs. Khuchua and Strauss developed tissue-specific knockout approaches and detailed physiologic studies in HL-75421.
Training Program in Pediatric Cardiopulmonary Research: 5T32 HL007256 | 07/01/77-06/30/07 | NIH/NIHLBI | Principal Investigator
This institutional training grant is for graduate students and post-doctoral fellows.
NICHD Institutional Training for Pediatricians: 1T32HD044328 | 06/01/03-04/30/08 | NIH/NICHD | Principal Investigator
This institutional training grant is for physician post-doctoral fellows to develop expertise in patient-based research.

Stipend and benefit Support is available to qualified candidates through NHLBI Training Grant: T-32 HL07382-30: "Training In Cardiovascular Biology", Dr. Arnold Schwartz, Principal Investigator.

Publications, Most Recent

Liebig M, Schymik I, Mueller M, Wendel U, Mayatepek E, Ruiter J, Strauss AW, Wanders RJ, Spiekerkoetter U. (2006) Neonatal screening for very long-chain acyl-coA dehydrogenase deficiency: enzymatic and molecular evaluation of neonates with elevated C14:1-carnitine levels.Pediatrics 118:1065-9.
Khuchua Z, Yue Z, Batts L, Strauss AW. (2006) A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function.Circ Res 99:201-8.
Exil VJ, Gardner CD, Rottman JN, Sims H, Bartelds B, Khuchua Z, Sindhal R, Ni G, Strauss AW. (2006) Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase.Am J Physiol Heart Circ Physiol 290:H1289-97.
Bennett MJ, Russell LK, Tokunaga C, Narayan SB, Tan L, Seegmiller A, Boriack RL, Strauss AW. (2006) Reye-like syndrome resulting from novel missense mutations in mitochondrial medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenase.Mol Genet Metab 89:74-9.
Strauss AW. (2005) Surprising? Perhaps not. Long-chain fatty acid oxidation during human fetal development.Pediatr Res 57:753-4.
Spiekerkoetter U, Tokunaga C, Wendel U, Mayatepek E, Ijlst L, Vaz FM, van Vlies N, Overmars H, Duran M, Wijburg FA, Wanders RJ, Strauss AW. (2005) Tissue carnitine homeostasis in very-long-chain acyl-CoA dehydrogenase-deficient mice.Pediatr Res 57:760-4.
Shekhawat PS, Matern D, Strauss AW. (2005) Fetal fatty acid oxidation disorders, their effect on maternal health and neonatal outcome: impact of expanded newborn screening on their diagnosis and management.Pediatr Res 57:78R-86R.
Djouadi F, Aubey F, Schlemmer D, Ruiter JP, Wanders RJ, Strauss AW, Bastin J. (2005) Bezafibrate increases very-long-chain acyl-CoA dehydrogenase protein and mRNA expression in deficient fibroblasts and is a potential therapy for fatty acid oxidation disorders.Hum Mol Genet 14:2695-703.
Browning MF, Larson C, Strauss A, Marsden DL. (2005) Normal acylcarnitine levels during confirmation of abnormal newborn screening in long-chain fatty acid oxidation defects.J Inherit Metab Dis 28:545-50.
Strauss AW. (2004) Tandem mass spectrometry in discovery of disorders of the metabolome.J Clin Invest 113:354-6.
Spierkerkoetter U, Khuchua Z, Yue Z, Strauss AW. (2004) The early-onset phenotype of mitochondrial trifunctional protein deficiency: a lethal disorder with multiple tissue involvement.J Inherit Metab Dis 27:294-6.
Spiekerkoetter U, Tokunaga C, Wendel U, Mayatepek E, Exil V, Duran M, Wijburg FA, Wanders RJ, Strauss AW. (2004) Changes in blood carnitine and acylcarnitine profiles of very long-chain acyl-CoA dehydrogenase-deficient mice subjected to stress.Eur J Clin Invest 34:191-6.
Spiekerkoetter U, Khuchua Z, Yue Z, Bennett MJ, Strauss AW. (2004) General mitochondrial trifunctional protein (TFP) deficiency as a result of either alpha- or beta-subunit mutations exhibits similar phenotypes because mutations in either subunit alter TFP complex expression and subunit turnover.Pediatr Res 55:190-6.
Spiekerkoetter U, Bennett MJ, Ben-Zeev B, Strauss AW, Tein I. (2004) Peripheral neuropathy, episodic myoglobinuria, and respiratory failure in deficiency of the mitochondrial trifunctional protein.Muscle Nerve 29:66-72.
McKinney JT, Longo N, Hahn SH, Matern D, Rinaldo P, Strauss AW, Dobrowolski SF. (2004) Rapid, comprehensive screening of the human medium chain acyl-CoA dehydrogenase gene.Mol Genet Metab 82:112-20.
Strauss A, Lock JE. (2003) Pediatric cardiomyopathy--a long way to go.N Engl J Med 348:1703-5.
Spiekerkoetter U, Sun B, Zytkovicz T, Wanders R, Strauss AW, Wendel U. (2003) MS/MS-based newborn and family screening detects asymptomatic patients with very-long-chain acyl-CoA dehydrogenase deficiency.J Pediatr 143:335-42.
Spiekerkoetter U, Sun B, Khuchua Z, Bennett MJ, Strauss AW. (2003) Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations.Hum Mutat 21:598-607.
Shekhawat P, Bennett MJ, Sadovsky Y, Nelson DM, Rakheja D, Strauss AW. (2003) Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases.Am J Physiol Endocrinol Metab 284:E1098-105.
Khuchua Z, Wozniak DF, Bardgett ME, Yue Z, McDonald M, Boero J, Hartman RE, Sims H, Strauss AW. (2003) Deletion of the N-terminus of murine map2 by gene targeting disrupts hippocampal ca1 neuron architecture and alters contextual memory.Neuroscience 119:101-11.
Exil VJ, Roberts RL, Sims H, McLaughlin JE, Malkin RA, Gardner CD, Ni G, Rottman JN, Strauss AW. (2003) Very-long-chain acyl-coenzyme a dehydrogenase deficiency in mice.Circ Res 93:448-55.
Zytkovicz TH, Fitzgerald EF, Marsden D, Larson CA, Shih VE, Johnson DM, Strauss AW, Comeau AM, Eaton RB, Grady GF. (2001) Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program.Clin Chem 47:1945-55.
Ibdah JA, Paul H, Zhao Y, Binford S, Salleng K, Cline M, Matern D, Bennett MJ, Rinaldo P, Strauss AW. (2001) Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death.J Clin Invest 107:1403-9.
Barycki JJ, O'Brien LK, Strauss AW, Banaszak LJ. (2000) Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase.J Biol Chem 275:27186-96.
Ibdah JA, Bennett MJ, Rinaldo P, Zhao Y, Gibson B, Sims HF, Strauss AW. (1999) A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.N Engl J Med 340:1723-31.

Professional Organization Memberships

Member, American Society of Clinical Investigation
Member and past Councilor, Society for Pediatric Research; Member, American Pediatric Society
Member, Association of American Physicians
Member and Chair, NIH Cardiovascular A Study Section, 1991-1994
NHLBI Task Force on Pediatric Cardiovascular Medicine, 2001
Associate Editor, Pediatric Research, 1989-1993
Editorial Board, Pediatrics, 2001-03.