Discovery and Mechanistic Study of Ultra-Rare Genetic Disorders
The Webb Lab has two goals: mechanistic investigation of ultra-rare genetic disorders and clinical genomic discovery through the Undiagnosed Disease Program. With a particular emphasis on neurodevelopmental and mitochondrial disease, the lab integrates human genomics, patient-derived models, and animal systems to move from gene discovery to biological mechanism.
Dr. Webb serves as Director of the University of Wisconsin Undiagnosed Disease Program, a Diagnostic Center of Excellence within the NIH Undiagnosed Diseases Network. Through this dual clinical–experimental framework, the Webb Lab bridges precision medicine and basic biology to transform unresolved patient cases into mechanistic insight.
An Overview of our Current Research
The Webb Lab studies the genetic basis and pathophysiology of rare Mendelian disorders, with a particular emphasis on undiagnosed disease, Moebius syndrome and related congenital facial weakness conditions, and mitochondrial disorders. Ongoing projects focus on ultra-rare neurodevelopmental and neuromuscular conditions involving MARS2- and WARS2-associated mitochondrial disease and POU4F1-related neurodevelopmental disorders. The lab develops and applies both cellular and animal models, including genetically engineered mouse models and patient-derived induced pluripotent stem cell systems, to define how pathogenic variants disrupt development and cellular function. These models are used to characterize altered transcriptomes, molecular networks, and tissue-specific vulnerabilities, linking human genetic discoveries to disease mechanism.
Latest Publications
