Dr Xiang Zheng, Assistant Professor in spatial proteomics at Aarhus University, is combining techniques to study cancer in unprecedented detail. Throughout his precision oncology research, which is advancing our understanding of how cancer develops and responds to treatment, Xiang has learned the value of interdisciplinary work and collaboration. It’s the combination of different perspectives and skill sets that advance scientific endeavours such as personalised cancer treatment – Xiang’s ultimate goal.

From medical student to cancer cartographer

Xiang’s journey began not in a lab, but in a medical classroom. As a medical student, he was already captivated by cancer. “I started my journey in cancer research combining clinical and research experience,” he recalls, “always driven by the desire to understand the intricate molecular adaptations driving cancer progression.”

A pivotal moment arose during his PhD at the Max Planck Institute, where he investigated how tumour-associated immune cells could be reprogrammed for therapy. He discovered that immune cells are not static soldiers, but dynamic actors whose behaviour dramatically changes depending on their spatial context within a tumour.

“I observed that immune cells do not function in isolation,” Xiang explains. “They are part of a highly dynamic, spatially regulated system.” This realisation became the cornerstone of his research—the understanding that to truly comprehend cancer, one must look beyond individual cells and examine their complex ecosystem.

His early research on reprogramming tumour-associated macrophages for lung cancer therapy revealed a crucial insight: “While analysing these cells, I observed that their plasticity varied markedly depending on their spatial location within the tumour,” he notes. This contrast highlighted that understanding spatial context was essential for decoding the molecular adaptations driving cancer progression and immune evasion.

Advancing spatial proteomics

This insight led him to develop mipDVP, an extension of Deep Visual Proteomics (DVP) that enables highly precise, single-cell-type proteomics. By integrating multiplexed imaging with mass spectrometry, Xiang has contributed to the development of approaches that enable the detection of thousands of proteins with unprecedented spatial resolution.

During his postdoc at the University of Copenhagen, Xiang addressed the limitations of targeted multiplexed imaging by creating this advanced technique. “The novelty lies in the technique’s ability to perform both broad and deep protein profiling,” he explains, “significantly advancing spatial proteomics and offering potential for identifying novel biomarkers and therapeutic targets in precision oncology.”

Some of his most striking discoveries emerged from unexpected places. In tonsil cancer, he found cytotoxic T cells with an unconventional phenotype—cells that had deviated from traditional memory and naïve T cell states. In colorectal cancer, he observed macrophages forming an immunosuppressive barrier, potentially restricting how immune cells interact with tumour tissues.

“It was a moment of realisation – immune interactions were far more dynamic and context-dependent than I previously assumed,” he says. “It was both exciting and humbling—reinforcing that even well-characterised immune functions could shift in unexpected ways depending on their spatial niche.”

This moment spurred in Xiang a deep motivation to explore the proteomic patterns underlying these adaptations, uncovering how immune cells respond to the tumour’s molecular cues.

Bridging the gap

One of his most memorable discoveries involved applying DVP to two real-world clinically complex cancer cases: composite lymphoma and signet ring cell carcinoma (SRCC). “These cases showcased the power of spatially resolved proteomics in revealing tumour heterogeneity and identifying potential therapeutic targets,” Xiang explains. The findings highlighted DVP’s potential not only in dissecting tumour complexity but also in pinpointing molecular vulnerabilities that could guide personalised treatment strategies.

To Xiang, this was a pivotal moment: “The realisation that we could extract clinically meaningful insights from archived tissue samples and potentially guide personalised treatments in these complex cancer cases was incredibly rewarding,” he recalls. “It felt like we were bridging a longstanding gap between basic research and clinical application—transforming a highly technical approach into something translationally relevant.”

Graphical abstract supplied by Xiang Zheng.

His technical innovations have been supported by cutting-edge tools and collaborations. When working with small sample amounts, having columns that provide consistent and reliable results has enabled Xiang to gain deeper insights into tumour biology and immune interactions. “The unmatched sensitivity that IonOpticks columns offer for miniaturised samples has been crucial in our clinical proteomics work, where biopsy material is often limited. Their ease of use and compatibility with low flow rates has been especially beneficial for my DVP-related work,” Xiang notes.

Read the full mipDVP paper here.

Overcoming technical challenges through collaboration

The path to these breakthroughs wasn’t without obstacles. “One of the most significant and technically demanding challenges I faced was maintaining the integrity of both the membrane slide and the tissue/protein after high-plex staining and imaging,” Xiang explains. Membrane slides are crucial for laser microdissection, but their fragility can lead to substantial protein loss during the cyclic staining and imaging process.

To overcome these technical hurdles, Xiang adopted a collaborative approach, adapting a method his colleagues from the Mann group at the Max Planck Institute for Biochemistry had optimised. “I didn’t feel overwhelmed because of the strong support from my mentor, Prof. Matthias Mann, and colleagues, including Associate Prof. Andreas Mund,” he shares. “They provided me with the opportunity and resources to systematically test different multiplexing platforms, staining conditions, and microdissection parameters.”

This strong network, which extended to clinical and pathological collaborators, gave Xiang the confidence in achieving a balance between high-plex imaging and proteomic sensitivity and minimise protein loss. His network of mentors and collaborators has also allowed Xiang to branch out beyond cancer:

“Thanks to the support of my current mentor, Prof. Robert A. Fenton, my postdoc mentor, Prof. Matthias Mann, and my collaboration with Prof. Lars Fugger, I have the opportunity to engage in spatial proteomics research not only in cancer but also in chronic kidney diseases and primary progressive multiple sclerosis.”

Image of Orbitrap Astral taken by the Mann group at CPR, University of Copenhagen

A look ahead: working towards personalised medicine

Looking forward, Xiang sees spatial proteomics as a key to unlocking personalisered medicine. “Personalised oncology means understand cancer in such detail that treatments can be tailored to the specific spatial and molecular characteristics of an individual patient’s tumour,” he explains. “My goal is to identify patient-specific vulnerabilities and predict treatment responses through deep molecular profiling.”

This approach is particularly promising for optimising immunotherapies, he believes. “The optimisation of immunotherapies relies on this level of precision—knowing which immune cells are present, how they interact with tumour cells, and what molecular mechanisms drive immune evasion or response.”

FFPE (Formalin-Fixed Paraffin-Embedded) samples harbour invaluable molecular and spatial information about tumour progression, treatment responses, and immune adaptations. “By applying high-resolution spatial proteomics, we can retrospectively extract this data, transforming archived tissues into clinically relevant datasets,” Xiang explains. “In essence, FFPE archives hold the potential to guide future therapies by providing a molecular roadmap of past patient outcomes—turning preserved tissue into a powerful tool for advancing precision medicine. Personalised oncology, biomarker discovery, and the optimisation of immunotherapies are turning every hospital’s FFPE archives into a therapeutic treasure trove.”

If there’s one thing that Xiang would tell his younger self, it would be to embrace interdisciplinary work sooner. “The application of DVP to real-world refractory cancer cases and the integration of multiplexed imaging into DVP were only possible because I worked across multiple fields—combining imaging, AI, microdissection, and proteomics,” he emphasises. “Science advances most rapidly when we draw from diverse expertise rather than limiting ourselves to a single niche. This enriches our understanding by combining different perspectives and skill sets.”

Now, with the full power of collaboration in his ever-expanding network, Xiang is setting his sights on turning his scientific insights into clinical reality.

Would you like to be featured in an upcoming Community Newsletter? Email us at [email protected] and tell us a bit about yourself and your research.