Andreas Metousis, a PhD candidate with Prof. Matthias Mann at the Max Planck Institute of Biochemistry, is advancing the field of mass spectrometry by applying it to medicine, with a particular focus on cancer research. At the intersection of bioinformatics and clinical applications, he is making significant advancements in understanding human neoplasia and the promising field of spatial proteomics.

The path to proteomics

After completing his BSc in Athens, Andreas ventured to Stockholm’s Karolinska Institute to pursue his MSc. It was there that he first encountered the different omics disciplines and found himself drawn to proteomics for its unique translational potential, as it examines the functionally relevant molecular actors of cells.

“Proteomics is pivotal in identifying diagnostic, prognostic or predictive biomarkers and uncovering novel druggable targets, which can significantly improve patient outcomes.”

Initially working with affinity-based proteomics, he quickly recognised its limitations and turned to mass spectrometry-based proteomics, which holds tremendous potential for translating research findings into tangible benefits for patients with neoplasia and other diseases.

“My vision is that medicine will become truly personalised, with clinical decisions guided by comprehensive omics data,” Andreas explains. “By mastering mass spectrometry proteomics, I aspire to be a part of this future.”

The rapid pace of technology

A moment that profoundly changed Andreas’ perspective was witnessing the rapid technological advancements in mass spectrometry.

“When I began my studies, the idea of conducting ultra-low input proteomics with any meaningful proteomic coverage seemed like a distant goal. However, within a relatively short timeframe, instruments have become more sensitive, faster, and more accurate, allowing experiments that were once deemed impossible.”

As an example, Andreas names the ability to perform single-cell and single-shape spatial proteomics on short gradients with extensive proteomic coverage.

“This has opened entirely new avenues for research. Observing the swift progress in mass spectrometry has not only expanded my research capabilities but has also reinforced my commitment to leveraging these cutting-edge technologies to drive innovations in cancer research.”

Today, his work focuses on cell type-resolved proteomics, using an innovative approach his group developed called Deep Visual Proteomics (DVP). This method not only allows for cell type resolution but also incorporates the spatial aspect of tissues. As Andreas explains, “DVP provides critical insights into the spatial distribution of proteins within tissues, an essential component in understanding the complex microenvironments of tumours. By integrating spatial biology, we aim to uncover new dimensions of tumour biology that can inform the development of more precise and effective therapeutic strategies.”

Breakthrough moments

One of the lab’s most significant recent breakthroughs came through a study on toxic epidermal necrolysis (TEN), a severe and often fatal drug-induced skin reaction. Working alongside lead author Dr. Thierry Nordmann, Andreas and team used DVP, which offers cell-type-resolved data, to analyse archived skin tissue biopsies from patients experiencing various cutaneous drug reactions.

The study revealed insights into the molecular mechanisms of TEN, testing the effects of targeting the cellular pathways involved in the condition with specific inhibitors. This led to the identification of JAK inhibitors as a potential treatment. Most compelling, to Andreas, was the observed safety and efficacy of JAK inhibitors in human patients.

He notes, “Treatment led to rapid re-epithelialisation and recovery in seven TEN patients. This discovery not only highlighted the JAK/STAT and interferon signalling pathways as key drivers of TEN, but also demonstrated the potential of JAK inhibitors as a curative therapy. This study represents a significant step forward in our understanding and treatment of TEN, showcasing the power of proteomics in uncovering viable therapeutic targets.”

Andreas discusses the Aurora Elite XT as the study’s column of choice for its robustness: “They can handle hundreds of samples while maintaining high performance. This durability means we can measure entire cohorts using the same column, ensuring consistent results.” He also calls out how well the columns integrate with the Evosep Whisper gradients the team use for sensitive and high throughput applications like DVP or single-cell proteomics.

Read the full study here.

The future of spatial proteomics

Looking ahead, Andreas is particularly excited about the advancement of spatial proteomics techniques. To him, the development of DVP represents a significant leap forward for this field, combining imaging and deep learning with mass spectrometry to provide high-resolution, single-cell type resolved, spatial, and unbiased proteome analysis.

“This integration allows researchers to gain detailed insights into cellular environments, revealing how proteins are organised spatially within tissues.”

Reflecting on the direction of the field, Andreas remarked: “The impact of spatial proteomics on biomedical research is profound, particularly in understanding diseases like cancer.”

It enables the examination of the tumour microenvironment and the roles that different cell types, such as immune and stromal cells, play in disease progression and therapy resistance. By illuminating these spatial interactions, spatial proteomics can guide the development of targeted therapies designed to interfere with harmful cellular behaviours or enhance beneficial ones, ultimately improving treatment outcomes.

“Overall, spatial proteomics is a game-changer for biomedical research. As technology advances, it will continue to unravel the complexities of cellular and tissue organisation, enhancing our understanding of disease mechanisms and playing a pivotal role in personalising medicine” – the very future Andreas envisions to build.

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