Sarah H. Elsea, Ph.D., F.A.C.M.G.

Professor, Molecular & Human Genetics

Sarah Elsea, PhD, FACMG Contact information

Other position

Advisor, Global MAPS, Baylor Genetics

Chair, Professional Advisory Board for PRISMS, Inc.

Board member, American Board of Medical Genetics

Board member, American College of Medical Genetics and Genomics Foundation


B.S., Missouri State University, Springfield, 1990

Ph.D., Vanderbilt University, Nashville, 1994

Postdoc, Baylor College of Medicine, Houston, 1998

ABMG fellowship training, Baylor College of Medicine, Houston, 1998

Research Interests

Despite many advances in the diagnosis of rare disease, the pathophysiological mechanisms underlying these disorders are poorly understood. Our research goals are targeted toward defining the biochemical mechanisms and molecular pathways impacted in human genetic disease. 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. 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. 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. 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. To further support these studies, we have created and maintain a Smith-Magenis syndrome patient registry and have other patient registries in development.

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. 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. 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. For example, one of the hallmark features of Smith-Magenis syndrome is a circadian rhythm defect. 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.

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. 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.

We have developed at Baylor Genetics a clinical metabolomics pipeline for diagnosis and management of inborn errors of metabolism. 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 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. 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.

While most of our studies have a molecular basis, we also work to educate others about rare disease and to provide parents, caregivers and siblings of individuals with neurodevelopmental syndromes with the tools they need to maintain healthy families. Our data show that families are doing very well despite the high prevalence of anxiety and depression among both mothers and fathers and that while younger typically developing siblings may have some difficulties, adult siblings are doing very well, with many choosing careers in education or healthcare for individuals with developmental disabilities. Our studies highlight not only disease burden but also illustrate the power of early and accurate diagnosis, the breadth of needs for individuals with rare disease and the resiliency of families and caregivers.