Observing cells in petri dishes, pipetting biochemical solutions into glass tubes — these images often come to mind when one envisions cancer research. But Assistant Professor of Engineering and Molecular Pharmacology, Physiology and Biotechnology Ian Wong has taken a more comprehensive approach in his lab that primarily focuses on the emergence, early spread and behavior of cancer cells.
By incorporating computation and biotechnology into biology and chemistry, Wong — who could not be reached for comment — has developed his own community of multidisciplinary researchers that are not only trying to enhance the field, but are doing so through a multitude of lenses, said Susan Leggett GS, a member of Wong’s lab.
As one of the biology specialists in the lab, Leggett began working with Wong as a graduate student shortly after Wong came to the University. Along with the rest of the group, she has focused specifically on carcinoma — one of the most prevalent types of cancer that affects many of the cells that composing the epithelial tissue lining the body, she said. Leggett has dedicated significant attention to epithelial-mesenchymal transition, a process in which these high-plasticity epithelial cells change to more closely resemble cells that can move more freely about the body and cause harm. Leggett said that EMTs have been identified in some cancer patient tissues and account for “a lot of the fundamental changes (of cancer cells) that are being quantified.” Looking ahead, she added that “if we learn some fundamentals about this process, perhaps why it happens, when it happens, how to control it or reverse it, now we might have some translation targets” or clinical applications.
The research at Wong’s lab has also led to the discovery that, upon stimulation, cells can migrate while staying together, Leggett said. The team has explored this phenomenon by studying cells in a three-dimensional environment resembling that of an actual cell, a task that falls into Thomas Valentin’s GS area of expertise.
Valentin, who has been in the lab since September 2014, works with biomaterials and 3D printing and has created 3D-printed hydrogels out of synthetic polymers. What makes these hydrogels unique is their ability to conglomerate on their own after being taken apart, as well as their tendency to react and move, Valentin said. More recently, the researchers designed hydrogels that do not degrade easily and can therefore be used to build structures, he added.
The team 3D prints using stereolithography, which operates differently from more common 3D printers, Valentin said. The lab’s printers use a laser that converts liquid plastic into solid plastic, unlike conventional printers that shoot out melted plastic. “There are very few labs that I know of, at least in the United States, that use this strategy of 3D printing. The benefits are that it’s very fast, but it requires more complex chemistry,” Valentin said. These printers in the lab are also relatively old — from the ‘90s — but by prioritizing accuracy, speed and flexibility, the researchers have continued to use them. “I go into it, and I can change every single parameter within the printer that I want. It’s 100 percent customizable,” Valentin added.
Wong’s lab then brings the work from the bench to the screen by approaching the 3D modeling of these cancer cells through computer science and mathematics. Utilizing microscopic images and data to create computational models, Dhananjay Bhaskar GS has worked on digitally and mathematically representing communication between, and movement of, cancer cells. Within this area of research, topology — the study of figures and points in space — can be applied to understand the spread of cancer cells, and 3D image segmentation can serve to graphically recreate and quantify the three-dimensional shapes of cells observed in the hydrogels, a difficult task for which Bhaskar is currently generating algorithms.
In their research, the group has faced significant challenges. In addition to a shortage of proper equipment, “when you write models for a cellular and tissue scale, you have to take into account things that happen at the subcellular level,” such as cell signaling and forces between cells, Bhaskar said. “The key challenge for me is to develop models in concert with a great experimental data analysis and to make sure my models are realistic when, in reality, I calibrate my models using images that are taken from the microscope,” he added.
There are difficulties in the biological component of the research as well, Leggett said. Cancer can vary in every patient, but the lab has made progress in identifying even subtle changes in cell structure or function. “We developed a platform to be able to detect on a single-cell level” when a cell has undergone EMT, Leggett said. This technique may be used to detect cancer in animals and patients in the future, she added.
The group also hopes to expand upon their work in the near future. The team is excited by the idea of putting “tumor cells in a context of different types of metastatic niches,” and studying how cells react in these environments, Leggett said. They also hope to find a way to use drugs to prevent or reverse EMTs, she added.
With the multitude of STEM disciplines mixed into Wong’s lab, the team hopes to continue to improve and innovate in the field of oncology. “I’d never thought I’d work in a biomedical engineering lab when I first came here, but I’m glad I did because … I got to gain a lot of different perspectives and kind of a new toolbox … especially with how interdisciplinary our lab is,” Leggett said. “When we meet as a group to discuss (the projects), … people are tackling it from different ways of thinking, and that to me can make the research more powerful,” she added.
Valentin was originally drawn to the mentorship in the lab. “The way (Wong) manages is hands-on and hands-off,” adding that “(Wong) doesn’t want to necessarily limit us to one singular focus, which is just cancer. He kind of lets us find our passion and keeps it relatively related to his wheelhouse.”