For William Matsui, M.D., professor of oncology and deputy director of Dell Med’s Livestrong Cancer Institutes, clinical research is not all that different from a game of Chutes and Ladders. They both involve twists and findings that accelerate progress and obstacles that revert advancements to earlier starting points. Like the game, research presents both a challenge and adventure to reach an end goal.
Through this lens, Matsui discussed his research career thus far in a Senior Scientist Seminar Series lecture, a quarterly event series hosted by the Health Transformation Research Institute that highlights researchers’ careers paths and impactful discoveries. What follows is a recap of his presentation.
On a Mission to Improve Health Outcomes
As a clinician-scientist, Matsui researches multiple myeloma, a common blood cancer that has a median survival rate of around five years. Recent outlooks anticipate an encouraging increase in survival, but the form of cancer is considered incurable in most patients due to a high likelihood of relapse. Wanting to make an impact on health outcomes, Matsui focused his early research on better understanding the factors that are responsible for relapse.
Through a series of experiments that toggled between basic, translational and clinical research, Matsui looked to identify and target specific markers on the cancer stem cells that survive myeloma treatment. He discovered a particular drug sensitivity and resistance pattern upon manipulating drugs that are commonly administered in myeloma treatment.
This discovery was a “ladder” up to understanding the mechanism of myeloma, and it led to further experiments that deployed a two-pronged approach to treatment. The approach: Reduce tumors and address the cells that may be responsible for relapse. The results of these experiments, however, were discouraging — they were a “chute” that slid his research team back to an earlier starting point and caused them to rethink what specific and significant markers of unwanted cell growth might address treatment. Fortunately, this setback ultimately proved to be a net positive for myeloma research.
A research group at the University of Pennsylvania worked in a similar field, and they continued refining Matsui’s two-pronged approach that showed promise, first harvesting and reintroducing a patient’s native stem cells (to repopulate healthy cellular regrowth) and then introducing modified T cells to reduce tumor size.
The results of these refinements were positive: A majority of samples responded well to treatment. The difference between Matsui’s research and that of the researchers at Penn? Matsui had the right target, but not the right targeting strategy. Now, in collaboration with the research group at Penn, Matsui and his team have set up clinical trials to explore myeloma recovery in relation to this treatment approach.
Advancing the Field Together
“We don’t have to prove everything ourselves,” says Matsui on the reiterative and collaborative process of research. “Find people you can convince and get excited about doing something that they’re experts in, and you can advance the field together.” Concluding his lecture, Matsui highlighted the collaborative opportunities that researchers at Dell Med and across UT have to connect the basic, translational and clinical research continuums of discovery.
He also encouraged the development of research support structures such as the Health Transformation Research Institute — which features educational opportunities centered around translational research — and he advocated for early faculty funding and ongoing seminars at the basic science level to help establish a strong basic-lab foundation.
To hear more stories about the captivating work being done by Dell Med clinician-scientists, view the institute’s seminar series calendar and attend an upcoming event.