David B. Goldstein, PhD
My research focuses on many aspects of human genetic variation including human genetic diversity, the genetics of disease, and pharmacogenetics. First at Duke University and now at Columbia University, my group, along with large networks of collaborators, has been responsible for a number of well-known discoveries including the gene responsible for Alternating Hemiplegia of Childhood and the role of the IL28B gene in treatment response to Hepatitis C infection. As Director of the Sequencing, Biostatistics, and Bioinformatics Core for the Epi4K Consortium, I have led the collaboration that discovered three novel epilepsy genes to date. My group has also been involved in some of the early applications of next generation sequencing in the study of undiagnosed diseases. In addition, my group developed a genome-wide scoring system ranking human genes in terms of their intolerance to standing functional genetic variation in the human population. We demonstrated that the use of this intolerance scoring system facilitates interpreting the clinical significance of mutations found in patients with serious genetic diseases.
My group also has a focus on understanding the molecular mechanisms associated with disease-causing variants. In the case of proteins implicated in epilepsies, multielectrode arrays (MEAs) are used to evaluate the effect of mutations on spontaneous neuronal activity. Using MEAs, candidate drugs can also be screened for their efficacy in returning mutant activity profiles to wild-type activity.