Becoming a Chemist
Chemist Derek Tan hopes that his group's research will be able to bridge the gap between basic science and the clinic, where it could someday help patients.
More interested in playing hockey, soccer, and tennis as a child than in playing with a chemistry set, Dr. Tan first developed his first real interest in chemistry when, as a freshman at Stanford University, he took an advanced chemistry course taught by two senior professors.
"They did a fantastic job of giving us an overview of all the different areas of chemistry, along with some of the current research, which really imparted a great deal of excitement for the field," Dr. Tan said.
Dr. Tan took his newfound interest in chemistry to Prof. Dale Drueckhammer's lab at Stanford, where he became attracted to research at the interface between chemistry and biology. He then joined Prof. Stuart Schreiber's lab at Harvard University to pursue his graduate studies.
Diversity-Oriented Synthesis – A Powerful New Approach
"As it turned out, I discovered it was difficult to do both chemistry and biology well at the same time," Dr. Tan noted. "So I shifted my focus to the chemistry side in a field that's now called diversity-oriented synthesis."
Diversity-oriented synthesis is an efficient method for generating libraries of thousands or even millions of small molecules. These molecules are then tested for their ability to probe biological systems. These small molecules can alter the function of particular proteins, providing a method to study their roles in biological processes. Importantly, small molecules initially identified as biological probes may also be used in the subsequent development of therapeutic agents.
"Although some such small molecule probes had been identified previously on an ad hoc basis, this program was really the first concerted effort to do this in a systematic fashion,"said Dr. Tan. "It was a very exciting time to be on the ground floor of this endeavor."
"I got to work with some wonderful people at Harvard, people who were so generous and helpful," added Dr. Tan. "This has really been a recurring theme throughout my career -- being fortunate to be surrounded by great coworkers."
Training Under the Best
After receiving his PhD, Dr. Tan was very excited about going into academic science, where he could start his own lab and work on more of his own ideas. "Rather than going the industrial route, I liked the flexibility and the freedom you have in academia," he noted.
After a brief discussion with Schreiber, the choice became very clear where he would do his post-doctoral work -- with Samuel Danishefsky, PhD, Kettering Chair and Head of the Laboratory of Bioorganic Chemistry at Sloan-Kettering Institute (SKI).
"I knew I wanted to solidify my training in organic synthesis, a field in which Sam is a master," explained Dr. Tan. "And I also knew that I wanted to maintain contact with biology, which Sam's lab does. And, finally, I wanted to go somewhere where I knew I could receive support for an academic position down the road, and Sam has an excellent track record for placing people into academia."
"The training in Sam's lab was great. I learned a lot of chemistry and was fortunate to be surrounded by a lot of outstanding colleagues and co-workers. When it came time to look for jobs, I saw an opportunity to combine what I had learned about natural products with Sam with the work I had done in Stuart's lab back at Harvard. I felt strongly that diversity-oriented synthesis was an emerging field, and the ability to use it to connect chemistry and biology was very appealing to me."
Finding a Professional Home
After going on numerous job interviews and receiving multiple offers, Dr. Tan decided to come to SKI for a number of reasons. "First, the resources here are clearly fantastic," he noted. "And there already was a large infrastructure of fantastic biology going on here. I had also met many people during the interview process who were very enthusiastic about finding small molecules to target their biologic systems -- not only as probes but, also, potentially as drugs."
And it wasn't only his colleagues who showed interest. Dr. Tan also took note of the institutional support for the expansion of chemistry at SKI and the development of small molecule probes. As a result, he started his own lab, the Laboratory of Chemistry and Chemical Genetics, in SKI's Molecular Pharmacology and Chemistry Program.
Research Goals
Dr. Tan's immediate goals are for his lab to develop syntheses of novel small molecule libraries. "These libraries are based on structural motifs from natural products, which save us from the problems associated with screening the natural products themselves. At the same time, we don't want to ignore the eons of evolutionary pressure that Nature has exerted on the development of these biologically active compounds." For this reason, he hopes to combine the best of both worlds, by incorporating structural motifs and synthetic design features from natural products into libraries of readily accessible compounds for screening and potential therapeutic use.
Dr. Tan explained: "We hope to impact both chemistry and biology through our research. First, we'd like to synthesize these libraries in a creative and efficient manner, developing new chemistry along the way. Then, working with our biological colleagues, we'd like to screen the libraries to identify new biological probes."
"Overall," he concluded, "I think that one of the most attractive features of this place is that, between the infrastructure in place and the potential for collaboration, we may be able to accomplish our ultimate mission, which is, if we're lucky, the creation of a new drug that can be used to treat and help patients. That is not a typical outcome for an academic chemist, and it's a huge motivating factor for us and our work."
