Cellular behaviour emerges from dynamic regulatory states of the proteome. Proteins do not simply exist as present or absent entities, but function as molecular systems capable of occupying multiple functional states. These states are shaped by post-translational modifications (PTMs), which regulate protein activity, stability, localization, and molecular interactions.

In this framework, proteins act as dynamic molecular switches—operating across a spectrum of combinatorial regulatory states. Each state reflects a specific configuration of site-specific PTMs, defining the functional biochemical state of a protein at a given time.

Our research focuses on decoding these regulatory proteome states. While individual PTMs can be measured, the integrated, high-dimensional PTM landscape that determines protein function remains largely inaccessible at scale.

Mass spectrometry–based proteomics provides a unique window into this regulatory layer. In the Nielsen lab, we develop and apply advanced MS-based technologies that enable large-scale, quantitative, and site-resolved mapping of PTMs directly in cells. Our work has contributed to methodological advances that make it possible to capture previously inaccessible aspects of PTM biology, and we continue to expand these capabilities toward increasingly comprehensive and high-dimensional measurements of regulatory proteome states.

By combining technology development in proteomics with mechanistic cell biology, we aim to reconstruct how dynamic PTM networks regulate biological systems. Ultimately, our goal is to uncover the principles by which regulatory proteome states govern cellular decision-making in health and disease.