Sophia Lunt’s biochemistry career started with soap. Fascinated by the chemical properties of soap taught in a high school science lesson, Lunt pursued degrees in chemistry, and then ventured into biochemistry for her postdoctoral research.
In 2019, when The Scientist first spoke with Lunt four years after she started her lab at Michigan State University (MSU), she was investigating the role of sugars in cancer’s spread.
To celebrate The Scientist’s 40th anniversary, we reached out to Lunt again to see the trajectory her research has taken over the last seven years. Along with looking at how metabolism impacts cancer metastasis, the scope of her work has expanded to explore light-activated drugs to destroy tumor cells. This work in photodynamic therapy led Lunt on an entrepreneurial journey to co-found a biotechnology startup.
This career trajectory “was completely unexpected,” said Lunt. “[It] has been really cool and very educational, exciting, and also sometimes challenging and overwhelming.”
From Metastasis Mechanisms to Light-Activated Cancer Therapy
For her work on cancer metabolism, Lunt joined forces with Sarah-Maria Fendt, whose research at Catholic University Leuven and Leuven Cancer Institute focuses on metabolic regulation in metastasis. Through their work, the researchers uncovered that the variable expression of the metabolic enzyme phosphoglycerate dehydrogenase (PHGDH) drives cancer growth and metastasis.1
Sophia Lunt and Richard Lunt often discuss science on their walks. It was during one of these conversations that the couple came up with the idea to engineer light-activated anticancer drugs.
Sophia Lunt
Lunt, Fendt, and their teams found that high PHGDH activity supports cancer cell proliferation. However, a dip in its protein expression leads to the biosynthesis of precursors that eventually help boost cell migration, helping tumors metastasize, and indicating that variable PHGDH levels are a potential sign of tumor aggressiveness. “That was very exciting,” recalled Lunt.
Continuing along the lines of her research interest in cancer biochemistry, Lunt also ventured into a relatively unconventional path of using light-sensitive drugs to target cancer cells. This happened serendipitously one day when she was on a walk with her husband Richard Lunt, a chemical scientist and materials engineer at MSU.
“He invented clear solar panels,” said Lunt. “He did this by using materials that only harvest near-infrared light and allow visible wavelengths to pass through.” During their walk, they brainstormed whether there was a way to get these clear materials to accumulate in cancer cells. Activating them with near-infrared light could then potentially lead to the production of reactive oxygen species (ROS) that would kill the cancer cells. “So, we tried to pursue this crazy idea,” said Lunt. “And it worked beautifully.”
The researchers began by tuning the optical and electronic properties of fluorescent organic salts.2 This rendered the molecules either nontoxic for imaging to aid cancer detection or phototoxic for therapy to attack cancer cells. Early studies in cancer cell lines indicated that the salts preferentially localized to the mitochondria to generate mitochondrial superoxide.
Upon testing the organic salts’ potential in a mouse model of breast cancer, Lunt and her colleagues found that the salts specifically accumulated in tumors.3 Exciting the molecules with near-infrared light led to inhibition of tumor growth with minimal side effects in vivo.
Fluorescence microscopy revealed that the photosensitizers (red) that Lunt helped engineer accumulated in cancer cells. Nuclei are depicted in blue.
Amir Roshanzadeh and Sophia Lunt
However, along with accumulating in tumors, the salts also gathered in the liver. But the liver does clear them in about 48 hours. “We wait for it to concentrate just in the tumor,” explained Lunt. “Then we shine near-infrared light on it.” Digging into the mechanism revealed that the molecules are taken up by organic anion-transporting polypeptides, membrane proteins that are highly expressed in cancer cells, which explains their long-term tumor-specificity.4
This technology offers an advantage over conventionally used light-absorbing drugs, which commonly require visible light. Visible light can’t reach deeper tissues, but near-infrared light can. Moreover, visible light leading to ROS production has another disadvantage. “Patients have to avoid light for about three months because the photosensitizer goes everywhere. So, light will basically cause [ROS], and the patients look like they have burns all over their body,” explained Lunt.
Learning the Language of Engineering and Entrepreneurship
While their photodynamic therapy seemed promising, the journey to create it was not straightforward, said Lunt. The first step was to convince people to work with them on the “crazy idea.” The project’s interdisciplinary nature required both biologists and engineers. “It's really cool to be truly interdisciplinary,” said Lunt, “taking solar energy research, combining it with cancer research, and actually making it work.”
But this came with its own challenges. Biologists and engineers working together meant they had to learn each other’s languages. “But at home, we would talk about it,” said Lunt. “[My husband] would teach me all the engineering terms and jargon…and then I would try to explain what's going on with cancer cells.” In this manner, not only did the Lunts adapt to each other’s fields, but they also helped their team members do the same.
When Sophia and Richard Lunt joined forces, they built a team of engineers and biologists to develop photosensitizers for targeting tumor cells.
Sophia Lunt
As the project progressed and they got promising results, they explored building a company based on their idea. By interacting with entrepreneurship mentors and grant writers facilitated by MSU, Lunt and her colleagues treaded into the relatively unknown waters of the entrepreneurial realm. “That part has been really exciting as well, just learning all of that,” said Lunt. “In addition to the engineering words, I'm learning all the business words.”
At their company Joule Therapeutics, Inc., Lunt and her team continue enhancing their photosensitizer molecules. At the moment, they are working on additional chemical modifications to test whether they can improve the efficacy of this treatment while also optimizing the light source required. “I hope we'll be able to actually develop this into a new therapy that will actually improve patient lives,” said Lunt.
Looking back, Lunt often finds it hard to believe that their idea conceived during a walk actually worked, leading to unexpected journeys in her career. “I never thought I would have the opportunity to think about molecules that absorb sunlight and how they might be tumor targeting, or I never thought I would think about entrepreneurship at all,” said Lunt.
“But that's the cool thing about research and life, right?” she added. “Sometimes opportunities present themselves, and you can follow them. And along the way you get to meet some really cool people, and it just leads to more amazing experiences.”
- Rossi M, et al. PHGDH heterogeneity potentiates cancer cell dissemination and metastasis. Nature. 2022;605(7911):747-753.
- Broadwater D, et al. Modulating cellular cytotoxicity and phototoxicity of fluorescent organic salts through counterion pairing. Sci Rep. 2019;9(1):15288.
- Broadwater D, et al. Counterion tuning of near-infrared organic salts dictates phototoxicity to inhibit tumor growth. ACS Appl Mater Interfaces. 2022;14(48):53511-53522.
- Roshanzadeh A, et al. Next-generation photosensitizers: Cyanine-carborane salts for superior photodynamic therapy of metastatic cancer. Angew Chem Int Ed Engl. 2025;64(9):e202419759.
