From Cancer Treatment to Cardioprotection and Tissue Regeneration

 

Modern medicine faces challenges that extend beyond treating diseases effectively. Equally important are minimizing treatment-related adverse effects and developing strategies to restore the structure and function of damaged tissues.

Cancer exemplifies these challenges. Despite substantial advances in cancer therapy, therapeutic resistance and tumor recurrence remain major obstacles to successful treatment. Furthermore, as cancer survival rates continue to improve, chemotherapy-associated cardiotoxicity and long-term cardiovascular complications have become increasingly important determinants of patient prognosis and quality of life.

 

Beyond disease control and injury prevention, another fundamental question deserves attention: Can we promote tissue repair and functional recovery by modulating cellular metabolism, microvascular circulation, and regenerative processes?

 

Although these challenges may appear distinct, they involve several interconnected biological processes, including cellular responses to stress and injury, mitochondrial energy metabolism, cell survival and death, and the regulation of the tissue microenvironment during repair and regeneration.

 

Our laboratory focuses on fundamental biomedical research, integrating molecular and cellular biology, pharmacological interventions, and in vivo zebrafish models to investigate the mechanisms underlying disease treatment, cellular protection, and tissue regeneration. By examining biological processes across multiple levels, from molecular signaling to organ function, we aim to generate mechanistic evidence that may inform the development of novel therapeutic strategies with translational potential.

 

Our current research encompasses three major areas.

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Research Direction 1: Overcoming Therapeutic Resistance in Difficult-to-Treat Cancers

Investigating Tumor Resistance and Developing Combination Therapies

 

One of the most persistent challenges in cancer treatment is the development of therapeutic resistance. Even when an initial response is favorable, residual cancer cells may survive treatment and subsequently drive tumor recurrence.

Our research focuses particularly on glioblastoma (GBM), an aggressive brain malignancy with limited treatment options and a high risk of recurrence. We investigate how tumor cells exploit DNA damage response (DDR) signaling and DNA repair mechanisms to survive the cellular damage induced by radiotherapy and chemotherapy.

Our approach integrates boron neutron capture therapy (BNCT), modulation of tumor cellular stress responses, and pharmacological inhibition of DNA repair pathways to investigate potential synergistic interactions among therapeutic interventions. By disrupting the mechanisms that enable cancer cells to tolerate and repair treatment-induced damage, we seek to enhance tumor sensitivity and identify effective therapeutic combinations capable of overcoming resistance.

 

Central Research Question: Can we exploit the dependence of resistant cancer cells on DNA damage responses and repair mechanisms to render otherwise refractory tumors more susceptible to treatment?

 

 

Research Direction 2: Protecting the Heart During Cancer Treatment

Elucidating Cardiotoxicity Mechanisms and Cardioprotective Drug Actions

 

Advances in cancer treatment have substantially improved patient survival. However, certain anticancer agents can cause cardiomyocyte injury, cardiac arrhythmias, and impaired cardiac function, potentially increasing the long term risk of heart failure.

Preserving anticancer efficacy while minimizing treatment associated cardiovascular injury is a central objective of cardio oncology, an increasingly important field at the intersection of oncology and cardiovascular medicine.

Our research investigates cardiotoxicity induced by anticancer agents, particularly doxorubicin, with an emphasis on the contributions of oxidative stress, mitochondrial dysfunction, impaired cellular energy metabolism, and regulated cell death to cardiac injury.

In parallel, we investigate the cardioprotective potential of pharmacological agents such as empagliflozin, focusing on their effects on cellular bioenergetics, mitochondrial quality control, and adaptive stress responses. These studies aim to determine whether modulation of these pathways can mitigate chemotherapy induced myocardial injury.

By combining cellular experiments with in vivo assessments of cardiac function in zebrafish, we seek to establish mechanistic links between molecular alterations and organ level physiological outcomes. Ultimately, this research may provide a scientific foundation for developing cardioprotective strategies that improve cardiovascular outcomes in patients undergoing cancer treatment.

 

Central Research Question: Can preserving mitochondrial function and cellular energy homeostasis reduce chemotherapy-induced cardiotoxicity and improve long-term outcomes in cancer survivors without compromising anticancer efficacy?

 

Research Direction 3: From Light to Microvascular Function and Tissue Regeneration

Investigating Photobiomodulation, Mitochondrial Bioenergetics, and Microvascular Perfusion in Tissue Repair

 

Following tissue injury, successful repair requires not only cellular proliferation and tissue remodeling but also adequate energy availability, microvascular perfusion, and coordinated interactions among different cell populations.

Photobiomodulation (PBM) has attracted growing interest in regenerative medicine as a potential approach to modulating cellular and tissue responses to injury. Light delivered at specific wavelengths and appropriate doses may influence mitochondrial activity, intracellular signaling, and local vascular function. However, the mechanisms through which light induced changes in cellular bioenergetics translate into improved microvascular function and tissue regeneration remain incompletely understood.

Using the remarkable regenerative capacity of zebrafish, we employ a caudal fin injury and regeneration model to investigate the effects of near infrared light (810 nm) on mitochondrial function, vascular endothelial cells, nitric oxide (NO) signaling, and microvascular blood flow.

Our research particularly emphasizes the functional interactions between mitochondrial energy metabolism and microcirculation. We seek to determine whether photobiomodulation can facilitate tissue repair by improving local perfusion, cellular energy homeostasis, and the physiological conditions required for regeneration.

 

Central Research Question: Can light mediated modulation of mitochondrial function and microvascular circulation activate or enhance the intrinsic regenerative capacity of damaged tissues?

 

 

Core Research Platform: Zebrafish as a Bridge Between Molecular Mechanisms and Organ Function

Zebrafish constitute a central experimental platform in our laboratory, particularly for investigating cardiotoxicity, cardiovascular physiology, and tissue regeneration.

Zebrafish share numerous evolutionarily conserved genes and physiological regulatory mechanisms with humans. Their embryos and larvae offer important advantages for in vivo imaging and developmental studies, while adult zebrafish possess remarkable cardiac and tissue regenerative capacities that are comparatively limited in adult mammals.

Our laboratory employs zebrafish models of cardiac injury, drug induced cardiotoxicity, and caudal fin regeneration to investigate the dynamic processes underlying tissue damage and recovery. These models enable integrated analyses spanning molecular signaling, cellular function, vascular circulation, and organ level physiological responses.

Compared with conventional mammalian models, zebrafish offer practical advantages in experimental efficiency and cost at selected stages of preclinical research. Their use can also contribute to the reduction of animal use in accordance with the principles of the 3Rs in animal research.

Through in vivo imaging, physiological measurements, and molecular analyses, we evaluate the biological effects of candidate drugs and experimental interventions while identifying mechanisms that warrant further investigation and validation in mammalian systems.

 

Our Research Vision: More Effective Treatments, Less Injury, and Greater Potential for Recovery

Although our three research directions address distinct diseases and biological challenges, they share a common scientific objective: to understand how cells respond to injury and how these responses can be therapeutically modulated to improve disease treatment, cellular protection, and tissue regeneration.

In cancer cells, we aim to disrupt the mechanisms that enable resistance to treatment.

In cardiomyocytes, we seek to strengthen protective mechanisms against drug-induced toxicity.

In damaged tissues, we investigate how cellular function and regenerative processes can be restored or enhanced.

Together, these research efforts examine the interconnected processes of cellular injury, survival, and repair from complementary perspectives, with the broader goal of translating fundamental biological discoveries into potential medical applications.

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Questions That Inspire Our Research

• Why do certain cancer cells survive intensive radiotherapy and chemotherapy, and how can their resistance mechanisms be overcome?

• Why can anticancer drugs effectively eliminate tumor cells while simultaneously damaging the heart? Can we protect healthy cells without compromising therapeutic efficacy?

• How does light influence mitochondrial function, microvascular circulation, and tissue regeneration?

• Why can zebrafish regenerate damaged cardiac tissue and caudal fins, and what can these remarkable abilities teach us about human medicine?

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We invite those interested in these questions to explore the relevant scientific literature and learn more about our research. We also welcome students and researchers who share our interests to join us in advancing biomedical knowledge and exploring its potential translation into clinical applications.