For more than 25 years, chemical and biomolecular engineer Denis Wirtz has pushed cancer research beyond flat cell cultures in petri dishes into three-dimensional models that better represent human physiology. Now, armed with artificial intelligence, he's transforming ordinary tissue biopsies into navigable 3D replicas—illuminating the hidden mechanics of how tumors form and spread, and opening pathways for developing new treatments that could save countless lives.
Wirtz is spearheading these efforts through a specialized interdisciplinary research center he helped establish at Johns Hopkins. Founded in 2022 with funding from the National Institutes of Health's National Cancer Institute, the Johns Hopkins Center for 3D Multiscale Cancer Imaging is a hub for interdisciplinary research and collaboration between engineers, oncologists, computer scientists, and pathologists working to decipher the complex behaviors behind deadly cancers.
"Our team tackles cancer from a fresh angle, creating cutting-edge computational approaches paired with sophisticated molecular techniques to pinpoint and visualize—in 3D—the critical cell-level processes driving the spread of cancer," said Wirtz, a core researcher at the Whiting School's Institute for NanoBioTechnology and vice provost for research at JHU.
Key to the success of the center's investigations is CODA, a groundbreaking computational program co-developed by Wirtz with Ashley Kiemen, an assistant professor at the School of Medicine, and Pei-Hsun Wu, an associate research professor in chemical and biomolecular engineering. CODA turns simple tissue samples into hundreds of images of ultrathin tissue sections and aligns them with precision, allowing researchers and clinicians to examine and manipulate them with unprecedented accuracy.
"These models give us the ability to view anatomical structures at the single-cell level, helping us home in on the exact location where cancer cells leave a tumor and enter the bloodstream to metastasize," Wirtz explains. "This approach is revealing new information about tumor formation, metastasis, tissue architecture, and cell behavior, which will lead to more effective diagnostics and treatments for a multitude of illnesses."
Image caption: Denis Wirtz, first row center, and team
Image credit: Will Kirk / Johns Hopkins University
For instance, Wirtz and his team have deployed CODA to image human fallopian tubes to identify early cellular changes that trigger ovarian cancer metastasis and also map the architecture of human skin. These federally funded efforts are yielding new insights. Notably, with support from the National Institutes of Health, CODA revealed that skin samples from people of similar age but different races and sexes have significant variations in roughness, thickness, fat content, and the size of hair follicles and nerves—findings that could fundamentally reshape our understanding of how diseases manifest across diverse populations.
Federal funding for Wirtz's work visualizing cell behavior in three dimensions began long before CODA was developed. From 2010 through 2018, the National Institutes of Health supported the Johns Hopkins Physical Sciences-Oncology Center, where Wirtz served as director. This funding led to a major discovery in 2017 that identified the key drivers of cancer metastasis: When cancer cells reproduce and create crowded conditions, they secrete two proteins that encourage them to move through surrounding tissue before hitching a ride on the bloodstream, allowing them to spread the disease to other parts of the body. Based on that knowledge, Wirtz's team has developed a unique therapy that directly targets the metastatic mechanism to inhibit cancer's spread and potentially improve outcomes for cancer patients.
"None of these discoveries would have happened without the sustained support for our research by the NIH," Wirtz said. "Federal funding has enabled our team to develop everything from our earliest visualization techniques to our current AI-powered ones, giving us critical information about how cancerous tumors form and spread. For the good of patients everywhere, we must continue this important work."
