Hideko Isozaki

Enzymes in focus: A molecular approach to stopping cancer before it starts

This feature explores how Professor Hideko Isozaki integrates clinical insight, molecular biology, and high-speed microscopy to prevent cancer drug resistance. Drawing on global experience and a patient-centered approach, her research at NanoLSI focuses on targeting the APOBEC3A enzyme to stop cancer evolution before it begins.　

From pharmacy to fundamental research

Professor Hideko Isozaki did not begin her career as a scientist. Originally trained as a pharmacist, she chose the profession because it offered flexibility and stability—a practical decision, especially for women navigating family and career.

“As a child, I dreamed of becoming a scientist,” she reflects, “but I thought research was for the brilliant or uniquely creative. It felt out of reach.”

Years later, after encouragement from her husband, Isozaki revisited that early dream. Transitioning from pharmacy to research, she brought with her valuable clinical insights. “Working with patients gave me a deep understanding of real-world medical needs,” she explains. “That perspective still shapes how I frame scientific questions today.”

 

 

Linking clinical insight and molecular mechanisms

Isozaki’s foundation in pharmacy, and her direct experience with a broad spectrum of diseases, allows her to approach cancer research with a holistic mindset. “Cancer is highly complex and individualized. Bridging clinical knowledge with basic research is essential,” she says.

Now at Kanazawa University’s Nano Life Science Institute (NanoLSI), Isozaki is focused on uncovering the molecular machinery that drives cancer evolution, particularly the role of the APOBEC3A enzyme.

A global lens forged in Boston

Her scientific vision was profoundly shaped by nearly seven years at Massachusetts General Hospital and Harvard Medical School. Immersed in a multicultural, collaborative environment, she led a small team and mentored young researchers. “The U.S. approach to open discussion and team-based science had a lasting influence on me,” she says.

Her time abroad also gave her greater appreciation for her Japanese identity. “Many colleagues had a deep interest in Japan. Their respect for our culture and science helped me see my background with pride,” she adds. This experience continues to inform her international collaborations today.

Targeting enzymes that drive cancer evolution

Isozaki’s recent research centers on APOBEC3A, an enzyme originally known for its antiviral activity but now recognized as a driver of genetic mutations in cancer. Her Nature publication revealed that deleting APOBEC3A delays the development of drug resistance in cancer cells [1].

“This was a pivotal discovery,” she explains. “Instead of waiting for resistance to occur, we can aim to prevent it by intervening at the source of mutation.” This preventative strategy marks a shift from traditional approaches that focus on treating resistant tumors after they emerge.

Her earlier work has also addressed mechanisms of drug resistance in lung cancer, including studies on acquired resistance to osimertinib and alectinib [2, 3].

Visualizing enzymes in action

At NanoLSI, Isozaki is leveraging high-speed atomic force microscopy (HS-AFM) to directly observe how APOBEC3A interacts with DNA. This real-time imaging technology offers unprecedented insight into how cancer evolves at the molecular level.

“Watching enzymes work in real time changes how we understand mutation,” she says. “It opens the door to precisely timed interventions that could stop resistance before it starts.”

This integration of physics and biology exemplifies the transdisciplinary strength of NanoLSI.

Finding a global community in Kanazawa

Returning to Japan after years abroad, Isozaki feared re-entering a narrow research environment. Instead, she found NanoLSI to be diverse, forward-looking, and globally connected. “I was pleasantly surprised,” she says. “The international atmosphere here reminds me of what I loved about working in Boston.”

The collaborative structure of the institute has helped her continue building partnerships across scientific fields. “It’s a place where clinical experience and cutting-edge microscopy can truly come together,” she notes.

Everyday inspiration outside the lab

Despite her busy research life, Isozaki finds inspiration in her personal time—especially through simple moments with her husband. “My favorite time is sharing delicious food and beautiful views together,” she says. “Those conversations often help me process challenges and think of new ideas.”

She also enjoys visiting hot springs and watching pandas, which offer joy and relaxation outside of the academic world.

A message for young scientists

To early-career researchers, especially women, Isozaki offers heartfelt advice: “Do not abandon your goals because of assumptions. Talk to people who support you. They may help you see a path forward.”

She also encourages honesty about one’s passions. “If you dislike what you’re doing, don’t force it. Do something that energizes you. That’s where real motivation comes from.”

With enzymes under the microscope and prevention as her mission, Professor Isozaki is advancing a vision of cancer therapy rooted in early intervention, global collaboration, and scientific curiosity that never stopped growing.

References

[1] Isozaki et al., Therapy-induced APOBEC3A drives evolution of persistent cancer cells. *Nature*. 620(7973):393-401, 2023.

[2] Piotrowska*, Isozaki* et al., Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion. *Cancer Discov*. 8(12):1529-1539, 2018.

[3] Isozaki et al., Non-small cell lung cancer cells acquire resistance to the ALK inhibitor alectinib by activating alternative receptor tyrosine kinases. *Cancer Res*. 76(6):1506-16, 2016.

 

Posted: July,2025