She is the associate director of the bioinformatics and scientific programming core at the National Human Genome Research Institute.

[2] Wolfsberg transitioned to computationally based research by performing a postdoctoral fellowship at the National Center for Biotechnology Information (NCBI) at NIH.

She worked as a staff scientist at NCBI before joining the National Human Genome Research Institute (NHGRI) faculty in 2000.

[1] Her research program focuses on developing methodologies to integrate sequence, annotation, and experimentally generated data so that bench biologists can quickly and easily obtain results for their large-scale experiments.

Her analysis of the Mnemiopsis genome helped to demonstrate that ctenophores are the oldest animal relatives of humans.