Oregon Health & Science University has received more than $9 million in National Institutes of Health funding to develop advanced microphysiologic models — also known as organs‑on-a-chip — that recreate how cancers grow, spread and respond to treatment within bone and bone‑associated tissues.
Two new awards, led by Alexander Davies, D.V.M., Ph.D., and Luiz Bertassoni, D.D.S., Ph.D., build on a $3.5 million NIH grant awarded to Bertassoni in 2025 and are affiliated with the Knight Cancer Precision Biofabrication Hub, a strategic initiative of the OHSU Knight Cancer Institute. Together, the three grants total nearly $9.2 million, establishing OHSU as a leader in using engineered human tissue models to study bone cancers and cancers that grow to the bone — an area of critical unmet medical need.
"These projects represent exactly what the Biofabrication Hub was created to do," said Bertassoni, professor of oncological sciences, bioengineering and dentistry and director of the Knight Cancer Precision Biofabrication Hub. "We are leveraging technologies developed here to study complex, aggressive cancers in ways that simply weren't possible before."
Organs-on-a-chip
All three NIH‑funded projects rely on microphysiologic systems, which are transparent devices about the size of a USB stick that contain living human cells arranged to mimic real tissues, including bone, blood vessels and distant organs such as the lung. These systems allow researchers to observe cancer behavior in real time, at single‑cell resolution, using human‑derived cells.
The approach addresses a longstanding challenge in cancer research: Traditional laboratory and animal models often fail to capture the complexity of how human cancers behave, especially when tumors spread to bone or distant organs.
"The NIH is prioritizing more human‑relevant models," Bertassoni said. "These devices allow us to generate that complexity in the lab and get at important questions we cannot study in patients."
Studying bone cancer spread
The award led by Davies, an assistant professor of oncological sciences and pediatrics in the OHSU School of Medicine, is for $3.17 million and focuses on osteosarcoma, a rare bone cancer that often affects children and adolescents. Survival rates for those whose disease has spread to the lungs have remained largely unchanged for more than four decades.
Davies' team will use engineered bone tissue and ex vivo lung models, combined with advanced imaging and biosensors, to watch osteosarcoma cells interact with bone and lung niches and respond to experimental therapies in real time.
"This is a rare disease that is very difficult to study using patient samples alone," Davies said. "Our models let us directly observe the metastatis — how tumor cells establish metastasis, communicate with their environment and respond to drugs — with a level of detail you simply can't achieve in humans."
The project builds on previous discoveries with collaborators at Nationwide Children's Hospital showing that osteosarcoma lung metastases may be vulnerable to drugs targeting a protein called MCL‑1, which helps cancer cells avoid dying.
In lab and animal studies, blocking MCL1 made it much harder for cancer cells to survive in the lungs. When MCL1 blockers were combined with cyclophosphamide, a standard chemotherapy drug, lung tumors were sometimes completely eliminated. These early results are encouraging, but scientists still need to confirm how specific and safe this approach is before it can be used in people.
To answer these questions, Davies and team will use advanced lab models that mimic human bone and lung tissue, allowing scientists to watch cancer cells grow, communicate with the surrounding tissue, and respond to drugs in real time. These models will help prove whether MCL1 truly drives survival of lung metastasis, and identify the best drugs to block it. The researchers will also test the safety of these drugs.
Davies said the goal is to develop safer, more effective treatments that target both cancer cells and their supportive environment, paving the way for future clinical trials and better outcomes for people with osteosarcoma.
How cancers invade, grow in bone
Prostate cancer has a strong tendency to spread to the bones. More than 80% of people with advanced prostate cancer develop bone tumors, which can cause severe pain, broken bones, and other serious complications.
A second NIH award of $2.5 million, led by Bertassoni, will focus on how aggressive prostate cancers grow to the bone. Using lab-grown bone tissues that include working blood vessels and nerves, his team will investigate how physical forces in blood vessels and signals from nerves help tumor cells lodge in bone and become more aggressive.
Using Bertassoni's highly advanced "bone‑on‑a‑chip" system, the newly funded project has two main goals. First, his team will study how the unique physical forces inside bone blood vessels help cancer cells escape into bone tissue and begin destroying it; they will closely examine how being squeezed affects cancer cells at the genetic level. Second, they will investigate how communication between nerves and cancer cells speeds up bone damage and tumor growth.
By combining bone, blood vessels and nerves in one realistic human model, this research creates the most complete lab system to date for studying how prostate cancer spreads to bone, Bertassoni said. The team's discoveries could reveal new drug targets to stop or slow bone metastasis and provide a powerful new tool for studying cancer spread.
"Bone is not a passive target," Bertassoni said. "Its blood vessels, nerves and mechanical properties actively influence whether cancer cells stop, survive and thrive. These models allow us to isolate and study those factors one by one."
The technology is also adaptable across cancer types. A previous NIH award to Bertassoni's lab supports similar studies in head and neck cancers that erode bone, demonstrating the versatility of the platform.
Interdisciplinary ecosystem
Together, the three grants reflect a deliberate investment by OHSU and the Knight Cancer Institute in interdisciplinary science, bringing engineers, cancer biologists, imaging experts and clinicians together to address complex diseases.
"This isn't serendipity — it's an ecosystem we've been building," Bertassoni said. "These connections are enabling better science, stronger funding and, ultimately, better care for patients."
Davies' grant was awarded by the National Cancer Institute, of the National Institutes of Health, under award number R01CA300732-01A1, with additional support from Sam Day Foundation and MIB Agents. Bertassoni's grants were awarded by the National Cancer Institute, of the National Institutes of Health, under award number R01CA310177, and the National Institute of Dental and Craniofacial Research, of the National Institutes of Health, under award number R01DE035326. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funders.
