The Scientist: Jeffrey Varner

It is hard to deny the progress that has been made by people who can “think outside the box.” Practically speaking, how do scientists, engineers and those in business learn to cultivate that special insight and intuition that transforms the dynamics of a problem into a more workable space? Asst. Prof. Jeffrey Varner, chemical engineering, did so by looking through the lens of a different academic discipline.

Dr. Varner spent his undergraduate and graduate years at Purdue University, first as an undergraduate in Math and Chemistry and then later as a Masters and Ph D. in Chemical Engineering. Today, he teaches graduate and undergraduate classes specializing in Biomolecular Engineering in chemical engineering at Cornell. Varner described his research focus as “understanding the molecular basis of cancers. Generally speaking, what we’re trying to do is understand how complex molecular programs that are involved in cells making decisions – like whether or not to grow, die, or simply do nothing [and] fail.”

“We study how networks break and how to break them.” Although he hopes to develop therapeutic treatments for cancer, Varner is also investigating other molecular signaling networks like blood clotting and the biochemical basis of pain. These two networks are of particular interest to the Department of Defense, which partially funds some of Jeffrey Varner’s research, in helping soldiers survive otherwise fatal wounds, such as extremity injuries. It also has civilian applications for afflictions like hemophilia and chronic pain.

Few people have asked how cancer is like a broken watch, or a failed mars mission, but these different problems have far more in common than most people would think. Varner likened complex systems to jumbo jets: “If a screw fails in your seat cushion, the airplane can still take off. However, if a screw fails in your engine and the engine falls off, you’re in serious trouble. At both points we’re dealing with the same faulty screws, but the context of the failure is different.” The screw in the engine is an example of a fragile point – one whose failure compromises the whole system – while the screws in the seat cushion are considered robust since the plane functions fine without them.

In a similar manner, Varner explained, many of a cell’s governing biochemical systems consist of robust points and fragile points. “One area we’re targeting for therapeutic purposes is translation.” Translation is the process by which short, “text message” copies of DNA called RNA are used to form ribosomes. The ribosomes in turn synthesize the proteins necessary for a cell to function. Once translation is stopped, a cell cannot carry on its normal functions and usually dies.

Translation also forms an integral part of the life cycle of cancerous cells. Varner’s team focuses on specialized proteins, called monoclonal antibodies, which can be engineered to only target certain types of cancerous cells.

Varner’s problem solving strategy is innovative. To identify and test new models, he looks at the relevant literature to find a molecular network of interest. “We then hire an army of undergraduates and we organize them into teams. Currently we have groups working on breast and prostate cancer, with nascent efforts in other areas.” The raw materials they use to construct these models are small sets of protein-protein interactions that represent pieces of the puzzle. “You can think about these as Lego blocks. We’ve already built the blocks and so we dump the blocks on the table and pull out the pieces we need and put them together and then test [the model] against data.” The benefit of this approach is that it takes advantage of the large body of existing data on biochemical reactions. “The same sort of systems are used over and over,” Varner said. “Nature didn’t reinvent the wheel.”

The elegance of the networks based approach is that it isn’t restricted to biological problems alone. “At the core of what we do is analyzing networks and figuring out how to break them.” This approach can be applied to other types of networks, such as ecosystems or social groups. From a conservationist’s standpoint, for example, it is very important to understand which elements of a food chain are most fragile and integral to the overall survival of a group of species. This knowledge could lead to better-directed protection effort. Terrorist networks can also be modeled as interdependent social groups with infrastructure and resource components that can be analyzed and tested in models to predict which actions would best neutralize threats.