Rong Li Lab

Rong Li, Ph.D.


Professor, Department of Molecular & Integrative Physiology
  The University of Kansas School of Medicine

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Look at a photograph of a busy freeway at rush hour, and what do you see? A colorful assemblage of cars, to be sure, and perhaps—if the resolution is good enough—frustrated expressions on drivers' faces. But missing from that static snapshot are all the intricate and dynamic interactions that actually define traffic patterns: the swerve of a semi in response to a passing motorist who cuts in too soon, the chain-reaction slow-down caused by a distracted driver who taps his brakes when his mobile phone chirps.

Meiosis II spindle (bright green) and cortical actin cap (shown in red). Chromosomes are shown in blue.

Image: Li lab.

Living cells, says Rong Li, are a lot like that freeway. In contrast to the tidy and inert diagrams of nucleus, cytoplasm, mitochondria and so on that we all studied in high school, cells are bustling bundles of matter, where various structures, signals and regulatory mechanisms interact in sometimes surprising ways.

"A cell is not like a static cartoon drawing," Li says. "A lot of what goes on in a cell is described by rates and the relative magnitudes of these rates; there are fluctuations, and there's some randomness in the amounts of various components and how they travel in the cell. We're interested in understanding, at a fundamental level, how such seemingly loosely interacting and fluctuating components work together to accomplish complex processes in a very accurate way, time after time."

That understanding could lead to entirely new approaches to treating and preventing disease. Currently, researchers often try to identify specific pathways involved in particular diseases and then find ways of inhibiting those pathways.

"That mentality could be fundamentally inadequate," Li says. "If you say you're going to inhibit this or that pathway, you're looking at the system as a rigid machine. What we're trying to do is not just ask what signals are operating and how the machine normally works, but to look at cellular processes—and diseases that result from errors in cellular processes—as very dynamic systems that can change and innovate."

Such systems have been shaped through evolutionary processes. So a key part of Li's research is exploring how the ability to evolve is built into cellular systems and how that ability, in turn, gives rise to a cell's properties.

In one set of experiments, Li's research group demonstrated that just as motorists on crowded freeways figure out alternate routes, cells can come up with creative solutions when they encounter roadblocks.

Normal retinal pigment epithelium-derived cells (green nuclei) stop dividing after the induction of tetraploidy, while carcinoma-derived HeLa cells (red nuclei) continue to proliferate, becoming large and multinucleated.

Image: Li lab.

The researchers deprived cells of components they normally need to divide and then watched to see what happened. At first, "the cells were in very big trouble," Li says. "They couldn't divide, and a lot of them died. But a few survived, and within several hundred generations they came up with bizarre but effective ways to solve the problem." The adaptation was possible because the cell is like "a big junkyard," full of parts that can be altered or assembled in different ways to serve a particular purpose. In this instance, a simple change in the number of copies of genes carried on certain chromosomes did the trick.

Interestingly, the trick the deprived cells came up with is one that cancer cells often use to increase their genetic diversity—the raw material of evolutionary change. Appreciating cancer cells' ability to evolve and adapt to conditions in the tissues they invade is essential to vanquishing the disease, Li believes. "Cancer is a moving target, and unless we understand how biological systems evolve and what they evolve toward, given the existing material in the cell, we may never be able to effectively treat cancer," she says.

Li's ability to think creatively about cellular processes, diseases, and their evolution may stem from her love of art, as well as her scientific savvy. As a child growing up in China, Li wanted to become an artist, and although she ultimately took a different career path, she sees parallels between her two passions.

"In both science and art, you observe, but you also have to feel," she says. "People think science is just about describing everything in numbers, but you have to have a feel for the system you're working with; you have to develop intuition. Often you can't directly see what individual molecules are doing, so you have to come up with indirect readouts and, just as in art, use imagination and creativity to capture the essence of the problem."