His interests are wide-ranging, with applications in such diverse areas as catalytic mechanisms, cell-specialization and other complex biological processes (normally studied by biologists, not chemists), basic photochemistry, biophysical probes of all stripes from NMR through positron-emission, and solid-state materials science.
Schultz then applied molecular diversity—the strategy of creating a large community of different molecules, plus a method for fishing out and identifying the ones that do what you want—to a range of problems in chemistry, biology and materials science.
For high-throughput bioassays which require freely soluble test-compounds, he uses microrobotic fluid-manipulation systems, adapted for 1,536-microwell cell-culture plates, to separately treat very small cell colonies with large numbers (hundreds of thousands) of different compounds.
[11] Using these various high-throughput and combinatorial experimental approaches, Schultz has identified materials with novel optical, electronic, and catalytic properties; also, proteins and small molecules which control important biological processes such as aging, cancer, autoimmunity, and stem-cell differentiation and de-specialization back to pluripotency.
Schultz has pioneered a method for adding new building blocks, beyond the common twenty amino acids, to the genetic codes of prokaryotic and eukaryotic organisms.
[17] One goal of this work is to culture the yeast-bacteria hybrids and see whether the bacterial genome evolves to increase the mutual benefits of its chemical interactions with the host cells, as has happened with mitochondria over time.
[18] Schultz and his team at the Calibr-Skaggs Institute for Innovative Medicines recognized that the chemical diversity and known safety profiles of drugs that had previously been tested in humans make them valuable to further explore for other potential therapeutic targets aside from originally intended use.
The library was created by combining three widely used commercial drug databases (Clarivate Integrity, GVK Excelra GoStar, and Citeline Pharmaprojects) along with patent mining of small molecules dosed in humans.
[19] The library found two compounds (VB-201 and a structurally related analog of ASP-7962) previously tested in humans for other therapeutic uses that subsequently showed to be effective in animal models of the infection, providing novel candidates.
Had it succeeded, this method could have become an essential tool for investigating the functions of carbohydrate attachments to proteins; however, the work could not be replicated, and when the lab went to find the relevant notebooks, they were missing.