Michael Wangler, M.D., Assistant Professor
Department of Molecular and Human Genetics,
Baylor College of Medicine,
Board certified, American Board of Pediatrics and American Board of Medical Genetics
Identifying and studying undiagnosed childhood genetic disorders
Dr. Wangler is a pediatrician and medical geneticist interested in childhood metabolic and neurological disease. Dr Wangler had the honor of doing pediatric residency at Texas Children's hospital under the late Dr Ralph Feigin. Dr Feigin's interest and enthusiasm for genetics has been a major motivator for the lab. The Wangler lab works according to the general principle that studies of patients with rare forms of human disease are where some of the strongest insights into human health have emerged. His laboratory focuses on three main areas of rare disease research.
First, the Wangler lab utilizes human genomics to try to identify the genetic causes of rare disease. The lab has been involved in a number of human gene discovery projects including genes like ACTG2, COL11A1 and AHDC1. Whole-exome sequencing is a powerful tool and identifying mutations in genes opens the door for a better understanding of disease.
The gene discoveries are often only the first step, thus in a second project the Wangler lab interfaces human genomic data with the model organism Drosophila melanogaster. Fruitflies have been an excellent genetic model for over 100 years and with the latest technology Wangler lab works to study specific genes and variants identified in patients in the fruitfly. This has ultimately been a large effort, requiring "team science" involving Hugo Bellen and Shinya Yamamoto labs at the NRI, Jim Lupski and Richard Gibbs with the Centers for Mendelian Genomics (http://mendelian.org/), Brendan Lee and Carlos Bacino and the Undiagnosed Diseases Network (https://undiagnosed.hms.harvard.edu/) Hsiao-Tuan Chao and Texas Children's Hospital, as well as the Simon's Foundation Autism Research Initiative. We are currently pursuing networks of genes implicated in Autism spectrum disorders and studying de novo mutations in patients with Autism and intellectual disability in the fly. This work has been funded for the creation of a model organism screening center which going forward will be a model for genomics and model organisms.
Finally, validation of genes and variants in flies can only provide early insights into genes, in order to understand gene function and get to new treatments for disease we need deeper analyses in humans and model systems. In a third project Wangler lab uses small molecule metabolic profiling or metabolomics for Peroxisomal Biogenesis Disorders and other metabolic disease. Peroxisomal Biogenesis disorders are a group of severe multisystem and neurological diseases due to loss of peroxisomes in the cell. Wangler lab has generated lipidomic and metabolomics profiles for Drosophila with peroxisomal mutations. In parallel, Dr Wangler is part of the Global Foundation for Peroxisomal Disorders and conducts clinical studies aimed at developing lipidomic and metabolomics profiles in PBD. These studies are aimed to provide a better understanding of how mutations in peroxisomal genes perturb the cell metabolism and lead to disease.
to see a complete list of Dr. Wangler's publications: