Dr. Alexander Laemmle's research focuses on establishing in vitro models to study rare genetic diseases. He applies induced pluripotent stem cell (iPSC) technology to produce patient-derived organ-specific cells. The generation of such disease models is a powerful tool to improve our understanding of the pathophysiology and to perform patient-specific drug screenings. One of his main interests is urea cycle disorders (UCDs) which belong to the group of inborn errors of metabolism (IEMs) affecting ammonia detoxification. The urea cycle consists of several enzymes which are located in hepatocytes. In UCDs there is a genetic defect in one of these enzymes causing potentially fatal hyperammonemia. Generating UCD patient-derived iPSC-hepatocytes (iPSC-Heps) enables to perform drug screenings in a patient-specific manner.
Dr. Barbara Marriage is a consultant in the area of paediatric nutrition. She was a Senior Associate Research Fellow leading the Paediatric Nutrition Science and Innovation group at Abbott Nutrition until May 2021 where she was responsible for clinical research and scientific support for paediatric products globally. She has held positions as Global Science Lead for Paediatric Specialty Nutrition, Associate Director in Global Regulatory Science and Innovation and Manager of the Paediatric Clinical Nutrition group. Dr. Marriage is a former graduate of the University of Guelph and completed her Master’s and PhD at the University of Alberta. Her PhD work was nutritional management of mitochondrial disorders. Before joining Abbott in 2002, she worked for over 20 years as a clinical research dietitian with extensive experience in paediatric nutrition and management of patients and families with inborn errors of metabolism. Her research interests include human milk oligosaccharides, gastrointestinal disorders, allergy and inborn errors of metabolism.
Ljubica Caldovic is a molecular biologist and biochemist with a focus on translating basic science discoveries into diagnoses and treatments for urea cycle disorders. She is leading the National Institutes of Health-funded Variant Curation Expert Panel that will establish relationships between DNA changes in the Ornithine Transcarbamylase (OTC) gene and OTC deficiency. Using a combination of bioinformatic and molecular biology approaches Dr. Caldovic identified disease-causing DNA changes in the regulatory regions of OTC and N-acetylglutamate (NAGS) genes. Dr. Caldovic cloned and characterized the human NAGS gene, the last mammalian urea cycle gene to be identified, and developed a molecular diagnostic test for NAGS deficiency based on that discovery. The molecular test was instrumental in identifying patients with NAGS deficiency, testing N-carbamylglutamate to restore ureagenesis in patients with NAGS deficiency, and FDA approval of N-carbamylglutamate for treatment of the disease in the US. Dr. Caldovic directs the Genomics and Bioinformatics Ph.D. program at the Institute of Biomedical Sciences at the George Washington University School of Medicine and Health Sciences. Dr. Caldovic completed her undergraduate work in Chemistry and Biochemistry at the University of Belgrade in Yugoslavia and her Ph.D. in the Molecular, Cellular, Developmental Biology and Genetics Department of the College of Biological Sciences at the University of Minnesota.
Hiroki Morizono is an expert in inborn errors of metabolism with a focus on urea cycle disorders beginning with his doctoral thesis: “The Biochemical Basis of Ornithine Transcarbamylase Deficiency” and is the current Director of Biomedical Informatics at the Clinical and Translational Science Institute at Children’s National Hospital. He has studied various aspects of Ornithine Transcarbamylase (OTC) deficiency for nearly three decades including building the first models to understand the three dimensional structure of OTC and producing recombinant OTC protein needed to solve the X-ray crystallographic structure of human OTC. He has been a curator for a database cataloging OTC variants to better understand the factors contributing to severity of OTC deficiency. Dr. Morizono is best known for being part of the preclinical AAV gene therapy team that evaluated the efficacy of vectors for treating OTC deficiency in animals. This vector is now in human clinical trials. From this work, he was also able to demonstrate that the genome editing tool CRISPr Cas9 could be used to provide protective levels of OTC gene conversion in a mouse model. Dr Morizono completed his undergraduate work in Life Sciences at MIT and his PhD in the Biochemistry, Molecular Biology, and Biophysics Department of the College of Biological Sciences at the University of Minnesota.