![]() Metabolomic profiling of more than 4500 clinical and research samples has provided functional output to support curation of genomic variants that has improved diagnosis and management of individuals with a variety of metabolic conditions and contributed to biomarker discovery in metabolic disorders. We are developing personalized medicine approaches for treatment of neurodevelopmental, neurogenerative and metabolically-driven conditions utilizing genomic, metabolomic and transcriptomic approaches to improve diagnosis, management and quality of life for individuals impacted by these conditions. Clinical and research studies have focused toward the development and utilization of metabolomic profiling and analysis of metabolic pathways toward biomarker discovery in a variety of inherited and acquired disorders. We have developed at Baylor Genetics a clinical metabolomics pipeline for diagnosis and management of inborn errors of metabolism. Utilizing cell culture model systems and conditional mouse models to improve understanding of the underlying etiology of these neurodegenerative and neoplastic mechanisms is a primary goal. New projects include investigation of the role of NAD kinase in both Alzheimer’s disease and pancreatic cancer and the role of this genetic and biochemical pathway in tumor growth toward developing personalized approaches to treatment. Our work has shown that RAI1 directly regulates CLOCK, a master regulator of circadian rhythm, providing strong evidence for molecular and cellular etiology behind the sleep phenotype and identifying a pathway that can be therapeutically targeted. For example, one of the hallmark features of Smith-Magenis syndrome is a circadian rhythm defect. Genes and pathways include RAI1, MBD5, HDAC4, TCF4, FMR1 and DEAF1, among others, with associated syndromes exhibiting commonly altered pathways, including circadian rhythm, metabolic and developmental gene networks that may be targets for therapeutic intervention. Current studies are focused toward understanding the molecular and cellular relationships between and among a subgroup of neurodevelopmental disorders with overlapping phenotypes using expression profiling, metabolomics and other functional approaches. In order to investigate the molecular and cellular basis of these rare, pleiotropic disorders, we have utilized a multidisciplinary approach including mouse, frog, zebrafish and human cellular models, including induced pluripotent stem cells and neural progenitor cells. To further support these studies, we have created and maintain a Smith-Magenis syndrome patient registry and have other patient registries in development. Our goals are to improve diagnosis, enhance understanding of phenotypes and develop a working knowledge of the molecular relationships among neurodevelopmental disorders developing toward targeted therapeutics. Disorders include Smith-Magenis syndrome, Potocki-Lupski syndrome, 2q23.1 deletion syndrome, 2q23.1 duplication syndrome, 2q37.3 deletion syndrome, Pitt-Hopkins syndrome, and others. This includes the clinical and molecular analysis of genomic conditions, wherein deletion or duplication of a portion of the genome is the primary underlying etiology, leading to altered gene dosage. The genetic analysis of neurodevelopmental disorders complicated by obesity and circadian rhythm defects, including autism, intellectual disability, seizures, and behavioral phenotypes, is a primary focus. Our research goals are targeted toward defining the biochemical mechanisms and molecular pathways impacted in human genetic disease. Molecular and biochemical basis of rare disease genomic disorders metabolomics diagnostics neurodevelopmental disorders caregiver concernsĭespite many advances in the diagnosis of rare disease, the pathophysiological mechanisms underlying these disorders are poorly understood. Houston, Texas United States Clinical Biochemical Genetics Certifications Clinical Biochemical Genetics American Board of Medical Genetics Professional Interests Houston, Texas United States Human molecular genetics Fellowship at Baylor College of Medicine Nashville, Tennessee United States Enzymology Postdoctoral Fellowship at Baylor College of Medicine Nashville, Tennessee United States Biochemistry Post-Doctoral Fellowship at Vanderbilt University ![]() Springfield, Missouri United States Chemistry, Biology PhD from Vanderbilt University Phone: (713) Education BS from Missouri State University United States Baylor College of Medicine (Lab) Graduate Program in Development, Disease Models & Therapeutics
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