She is involved in both basic and applied research and has had extensive experience working with photosynthetic organisms.

Dr. Ghirardi's work at NREL involves photobiological hydrogen production and covers metabolic, biochemical, and genetic aspects of algal metabolism.

Dr. Ghirardi co-discovered a sulfur-deprivation process, which allows sustained hydrogen production from algae. In addition, her team identified three enzymes required for the assembly of [FeFe]-hydrogenases, which led to the development of a bacterial system for production of large quantities of active algal hydrogenase enzyme, a major breakthrough in research. They also initiated the use of molecular dynamics to create computational simulations of O2 and H2 gas diffusion through the hydrogenase enzyme, which led to the identification of two access pathways for O2 to the catalytic site of the enzyme.