Positions

Assistant Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US

Education

MD from Baylor College Of Medicine
Internship at Baylor College Of Medicine Affiliate Hospitals
Pediatrics
Residency at Baylor College Of Medicine Affiliate Hospitals
Pediatrics
Residency at Baylor College Of Medicine Affiliate Hospitals
Clinical Genetics

Certifications

American Board of Pediatrics
American Board of Medical Genetics

Professional Interests

  • Pediatric genetics
  • Peroxisomal disorders

Professional Statement

Molecular and Developmental Mechanisms of Mendelian Disorders.

Studies of the basic mechanisms of Mendelian diseases offer insight into general principles that underlie human biology and disease. The overall long-term goal of Wangler Lab is to improve our understanding of the molecular pathogenesis of Mendelian disease by merging clinical observations, genomics and studies in model organisms particularly Drosophila melanogaster. We are currently using Drosophila to study Mendelian disorders and their underlying genetic and developmental mechanisms in two major efforts:

Model Organisms and the Molecular Pathogenesis of Mendelian Disorders: Genomic sequencing is an increasingly powerful tool for identifying the genetic basis of human developmental disorders. Genomics in humans creates the unique problem of the discovery of numerous rare variants in every genome. Without a clear understanding of gene function and the role of genes in development these variants are difficult to interpret. We began developing an approach to use Drosophila to understand gene function in development and in disease. Initially our efforts involved studying novel genes by working simultaneously with a large forward genetic screen in Drosophila and a genomic database from 2,000 individuals ascertained for Mendelian disease. This rich resource allowed for numerous links between Drosophila neurobiology and Mendelian disorders (Yamamoto et al., 2014), and this approach has been an impetus for emphasizing the tremendous value of model organism and Drosophila studies (Wangler et al., 2015). We have recently developed an efficient pipeline using Drosophila melanogaster to screen many conserved genes and variant of interest from genomic sequencing studies. We have successfully applied these tools to solve cases in the Centers for Mendelian Genomics (www.mendelian.org), and we are currently applying this pipeline to developmental brain disorders such as Autism by studying genes from the Simons Simplex Collection as well as unsolved cases from the Undiagnosed Diseases Network (UDN).

Mendelian Disorders of the Peroxisome and Organelle Dynamics: Human peroxisomal disorders exhibit numerous developmental and neurological features that illustrate the overall importance of peroxisomal metabolism in multicellular organisms. We use Drosophila and human samples to study the function of peroxisomal genes. This work has identified unique human phenotypes such as a late-onset ataxia associated with PEX16 (Bacino et al., 2015) that offer new insights into particularly hypomorphic alleles. We have also studied cases of infantile encephalopathy due to DNM1L mutations (Chao et al. 2016) by using a combination of human studies and expression of the human variants in Drosophila. The study of these mutations in flies has allowed us to understand loss and gain of function alleles in peroxisomal disease and broadened our understanding of these phenotypes and their biological basis. By studying rare disorders of the peroxisome and their impact on other organelles like mitochondria we gain insight into general principles of metabolism and disease.

Selected Publications