New COP chemist pushing boundaries of drug discovery

John Lennon once said, "Life is what happens to you while you're busy making other plans."

This was the case for new COP Assistant Professor Eli Chapman in 2003 when he was completing his scientific investigations for Scripps Research Institute, at La Jolla, Calif.

Chapman was a senior scientist when he got roped into teaching a class on protein folding, protein unfolding and macromolecular mechanics.

“I truly have a love for macromolecular machines,” Chapman says. “There is just something beautiful about them."

Macromolecular mechanics takes a close look at large protein complexes, which carry out specific biological functions in the human body. These protein complexes have many moving parts which scientists like Chapman are very interested in studying, such as how they work, what they look like, how they carry out their function, and how medically relevant they are.

Protein folding are processes where a random coil of amino acid monomers (molecules that chemically bind to other molecules) known as a polypeptide are translated into a linear structure of amino acids which interact with each other to construct a protein. That same protein can also be unfolded or unraveled by natural or artificial means.

"You know I spent five years studying protein folding and I really didn't know why you'd ever want to unfold a protein," Chapman says. "You have to have a highly tuned and highly controlled approach, but I fell in love with it."

From there Chapman's passion for chemistry and science only amplified his work, making him a top candidate for the assistant professor position in the college’s Department of Pharmacology and Toxicology. Chapman joined the faculty here last month.

“I have no doubt that in the future here we’ll have to fight off competition for him,” saysTerrence Monks,  department head.

Chapman and his laboratory team are interested in how large protein complexes, such as a protein folding machine like mitochondrial Hsp70, assemble and disassemble certain things inside the human body. Mitochondrial Hsp70 is a family of expressed heat shock proteins, which help protect cells from elevated temperatures or stress.

He will work closely with graduate and undergraduate students to find out more on how these machines work, and how they could be targeted.

Macromolecular machine P97 also has been a specific focus of Chapman's study. P97 is another large protein complex that carries a number of cellular functions that can replicate or degrade a misfolded protein.

According to Chapman, recent theory suggests that P97, due to the positioning of the proteasomes, may be a possible target to treating cancer. Proteasomes are cylindrical protein complexes that are crucial in the concentration of specific proteins and degrade misfolded proteins.

Drug discovery and small molecule drug discovery are two other main focuses of Chapman’s research.

As the rate of new drug discoveries continues to decrease, scientists have a harder time discovering new drug therapies. One of Chapman's goals at COP is to change the way scientists are approaching drug discovery by developing tools to facilitate it.

According to Chapman, there are so many classes or families of proteins that it becomes very hard in a standard drug platform to differentiate one from another. There are over 107 phosphatases in the body involved in many signaling pathways. A phosphatase is an enzyme that removes a phosphate group (inorganic chemical, such as salt) from the molecule it is having a reaction with.

Chapman is looking for a way to increase specificity with a new paradigm of drug discovery that can facilitate finding specific inhibitors.

In addition to his research, Chapman this year will teach in the course Drug Discovery, Design and Development. The class will be team taught by a band of professors.

Story by Isaac Cox
Home-page photo by Lida De Groote