Research in the Roth lab focuses on discovering drug-like small molecules that have interesting biological properties and then determining the mechanisms by which they act. This is a research strategy that is logically identical to classical forward genetics, with the difference that we identify a bioactive chemical rather than a mutation in a target gene. Like classical genetics, we let nature tell us what biology is most relevant to a process.

An advantage to this is that we are not limited to making guesses from what has already been discovered. Our experiments probe all of the biological space, not just the corner we know about.

Recently we have discovered chemicals that act on host cell processes to prevent virus infections, chemicals that selectively kill some non-small cell lung cancer but not normal cells, and chemicals that suppress the production of glucagon by an alpha cell line. Currently we are investigating the mode of action of these chemicals as well as determining their molecular targets.

In collaborations with chemists and pharmacologists at UT Southwestern, we are trying to improve the potency and pharmacological properties of these chemicals so that they might become useful leads for developing therapeutic drugs.