New theoretical model could develop novel clinical decision making in cancer research

Dan Schonfeld is a leading expert in image and video analysis, and he is applying some of the tools of his specialty to try to nudge genetic behavior in ways that may someday cure disease.

Schonfeld, a University of Illinois at Chicago professor of electrical and computer engineering, is studying gene expression and interactions in ways that are analogous to the workings of electrical or computer networks. He is project director and principal investigator of a four-year, $1.2 million National Institutes of Health grant.

"The idea is that DNA gives expression to proteins, and the amount and level of proteins dictates the state of the organism," Schonfeld said. "If the expression level of one DNA goes up, it might reduce the expression level of another. There is this symbiotic relation between the genes in a network and the expression level of each of the proteins depends on one another."

Schonfeld sees this dynamic behavior leading to production of either good or bad proteins. He envisions that using the tools of mathematics and engineering will lead to a method to control this protein production. To do it, he and his colleagues model gene regulatory networks as a Markov chain -- a statistical modeling tool often used in software development. They monitor the network over time and make slight changes or perturbations that may provide a degree of control.

"We've actually formed a new sub-area of inverse perturbation theory where we say we know where we want to go, what is the smallest change in the network that we need to impose in order to guarantee that wherever we are, we're going to end up where we'd like to be," he said.

Schonfeld said his goal is to take the results of mathematical analysis, transform it into a protocol for making small changes by putting certain chemicals into the cell resulting in a small change in the network, and then monitor its behavior over time to see whether it produces results predicted from the mathematical analysis.

Their theoretical model will be tested on melanoma cells using RNA interference and plasmid molecules designed to regulate the expression levels of specific genes in a melanoma network.

"We need to perturb and affect the influence of one gene on the other in order to move it in a better direction," he said. "The successful outcome of the proposed approach to the treatment of malignant melanoma cells could serve as a foundation for development of intervention strategies in other cancer networks."

Schonfeld said an interdisciplinary approach is "essential to an effective plan for developing novel treatment and clinical decision making in cancer research." His collaborators are Nidhal Bouaynaya, assistant professor of systems engineering at the University of Arkansas at Little Rock (a former Ph.D. student of Schonfeld's at UIC); and Hassan Fathallah-Shaykh, associate professor and chair of neuro-oncology at the University of Alabama at Birmingham (a UIC Ph.D. alumnus in mathematics).