Damian Young

Robert P. Doherty, Jr. - Welch Chair in Science, Baylor College of Medicine

Damian Young, assistant professor and Welch Chair at Baylor College of Medicine, is a synthetic organic chemist by training. Today, he looks to adapt the principles of natural product synthesis and modern organic chemistry to achieve total chemical synthesis of more complex molecules.

His research focuses on the development of chemical pathways leading to molecules that can be used to probe fundamental and disease-associated biology, pioneering new chemical and biophysical methodologies.

Dr. Young’s lab develops collections of small molecules, fragments of 200-300 molecular weight, with different three-dimensional shapes and features, yet essential similarities. Using synthetic chemistry tools, his team can make controlled and methodical changes in molecular features such as core scaffold, regiochemistry, stereochemistry and appendage substitutions to generate complete matrices of compounds varying in these features. The end result is libraries of these small molecules with systematic chemical diversity.

To leverage these libraries, Dr. Young has pioneered two screening paradigms: Fragment-Based Drug Discovery (FBDD) and DNA-Encoded Libraries (DELs). The goal is to rapidly and cost-effectively screen billions of small molecules to identify promising leads.

The FBDD approach screens molecules about half the size of a typical drug-like molecule. Such fragments typically can bind more efficiently to the smaller nooks and crannies of proteins than full-fledged drugs can, but the connection is weak. Once a potentially useful fragment is discovered, the team “grows” it in an optimal compound with high potency.

“Our goal is to synthesize fragments that are three-dimensionally complex, resembling the types of features seen in natural products,” Dr. Young said.

With DEL, his lab attaches a unique piece of DNA code (akin to a barcode) to each molecule.

“We then can take a protein and mix it with seven billion of the compounds in one test tube. We see which molecules bind to the protein, pull them out by their DNA handle and sequence them,” Dr. Young explained. “The next step is to test the most promising candidate drugs in experimental models such as fruit flies, mice, and human neuron cultures. This approach has allowed us to create a drug discovery pipeline that rivals any pharmaceutical company for a fraction of the cost.”

“The Welch Foundation is an amazing organization,” Dr. Young said. “It allows us to test very new and crazy ideas where we are basically in the dark based on not much more than our intuition. When one of those ideas pays off, it can open up new avenues of research and help create the new technologies needed to explore them. This is the kind of high-risk, high-reward science we can do here in Texas thanks to Welch.”