Interview with Professor Georgios Vougioukalakis

My fascination with synthetic and materials chemistry began during my undergraduate and post-graduate studies in Organic Chemistry at the University of Crete, the University of Sussex, and the Italian National Research Council, but it was truly ignited during my postdoctoral work at Caltech. Working with Professor Robert H. Grubbs, one of the pioneers of olefin metathesis, showed me how elegant molecular design could solve real-world problems. When I established my research group at NKUA in 2014, I focused on sustainable catalysis and the synthesis of compounds with biological and technological applications.

The path into cancer research came naturally through recognizing that chemistry could address one of humanitys greatest challenges. The SCALPEL project represents the convergence of my expertise in organic synthesis with the urgent need for better cancer treatments. When we began collaborating with photobiologists and immunologists, I realized that the molecules we design in the lab could literally save lives by enabling revolutionary treatments like photodynamic therapy combined with immunotherapy.

Chemistry is the language of life at the molecular level, and cancer is fundamentally a disease of molecular dysfunction. In SCALPEL, we are not just making molecules; we are designing precision tools that can distinguish healthy tissue from cancerous tissue with exquisite selectivity. Our innovative method uses light-activated click chemistry to tag and destroy cancer cells with exceptional accuracy, while helping the body prevent future recurrence.

This exemplifies why chemistry drives innovation in cancer treatment today.

Unlike broad-spectrum approaches, we can now engineer molecules that remain completely inert until activated at precisely the right place and time. The 2022 Nobel Prize in Chemistry recognized click chemistry for exactly this reason: it enables us to build molecular systems that function with biological precision. Every bond we form, every functional group we install, serves a specific purpose in the therapeutic strategy.

Precision medicine and immunotherapy are indeed transforming oncology, but SCALPEL pushes beyond current paradigms by combining three powerful approaches: photomedicine for targeted tumor destruction, click chemistry for precise molecular recognition, and immunotherapy for systemic cancer elimination.

While current precision medicine relies on identifying existing biomarkers, we are creating new biomarkers through controlled chemical modification of cancer cells. This represents a shift from passive recognition to active labeling of diseased tissue. Similarly, while traditional immunotherapy depends on the immune system recognizing cancer cells, SCALPEL chemically flags surviving cancer cells after photodynamic treatment, essentially teaching the immune system what to attack. We are not just following trends; we are creating new ones by showing that chemistry can bridge photomedicine and immunology in ways previously unimaginable.

Leading the chemical synthesis work package has been both exhilarating and challenging. The biggest opportunity lies in the creative synergy that emerges when chemists, photobiologists, immunologists, and protein engineers collaborate. Each discipline brings unique insights that push the others beyond their comfort zones.

The greatest challenge is establishing a common scientific language. When I design a new molecular scaffold, I must consider not only its synthetic feasibility, but also its cell incorporation kinetics, photosensitizer compatibility, and immunological implications. This requires constant dialogue with our Norwegian colleagues doing photodynamic therapy, our Slovenian partners engineering antibodies, and our French collaborators studying immunogenic cell death. \n\nSuccess in interdisciplinary work demands intellectual humility, that is, recognizing that your expertise, while essential, is just one piece of a larger puzzle. It also requires exceptional communication skills to translate complex synthetic strategies into terms that biologists and clinicians can understand and contribute to.

The journey from laboratory synthesis to clinical application involves several critical transitions. First, we must demonstrate that our molecular designs work not just in ideal conditions, but in the complex biological environment of living cells and tissues. This requires extensive optimization of synthetic routes to ensure reproducible, scalable production.

Regulatory approval presents unique challenges for SCALPEL, because we are combining multiple novel components in a completely new therapeutic modality. We must establish safety profiles for each component individually and in combination, while demonstrating efficacy across multiple animal models before human trials. \n\nFinally, manufacturing scalability is crucial. Our synthetic routes must be not only efficient, but also environmentally sustainable and economically viable.

Europes strength lies in our collaborative spirit and long-term vision for public health. The SCALPEL consortium exemplifies this: bringing together institutions from Norway, Greece, France, Slovenia, and Germany, each contributing unique expertise, while sharing a common goal. This cross-border collaboration would be difficult to replicate elsewhere.

European funding mechanisms like Horizon Europe enable high-risk, high-reward research that might not receive support in more commercially-driven systems. Our approach requires patience and substantial investment before showing results; the kind of fundamental research that Europe excels at supporting.

Moreover, Europes regulatory frameworks, while rigorous, are designed to protect patients while enabling innovation. The European Medicines Agencys scientific advice procedures help us understand regulatory requirements early, potentially accelerating the path to clinical application.

In ten years, I envision chemistry evolving into an even more precise tool for cancer therapy. We are already seeing the emergence of Chemical Biology approaches that blur the lines between synthetic molecules and biological systems. SCALPEL represents an early example of this integration.

I am particularly excited about the potential for artificial intelligence to accelerate molecular design. Machine learning algorithms could help us predict which chemical modifications will yield optimal tissue selectivity, photochemical properties, and immunological responses, dramatically reducing development timelines.

The concept of "programmable medicine", where we can design molecular systems that execute complex therapeutic programs within the body, represents the ultimate goal. SCALPEL is a step toward this future, demonstrating that chemistry can create sophisticated molecular machines for precisely targeted therapy.

Every synthetic chemist dreams of creating molecules that matter. But working on SCALPEL has shown me that chemistry can be literally life-changing. When I design a new clickable pair I am not just solving an intellectual puzzle; I am potentially creating tools that could cure cancer.

To my students and young researchers at NKUA, I want to convey that fundamental chemistry research is not separate from addressing humanitys greatest challenges; it is essential to solving them. The most elegant molecular architecture means nothing if it doesnt ultimately benefit human health and well-being.

What drives me is the possibility that a molecule designed in our Athens laboratory could one day help a child in Oslo, a grandmother in Ljubljana, or a father in Paris beat cancer. That potential impact makes every late night in the lab, every failed synthesis, and every difficult collaboration worthwhile. Chemistry has given us the tools to fight cancer at the molecular level; we just need the creativity and persistence to use them effectively.