Abigail Walton

I am from the UK and currently a PhD student in the Uhlén lab, supervised by Professor Per Uhlén and Dr. Shigeaki Kanatani. My research focuses on developing innovative technologies for 3D histology, with applications in oncology diagnostics and neuroscience research.

3D histology

Conventional histology has been the standard method for obtaining molecular readouts while preserving spatial information, or the microanatomy of tissue structure. This process involves serial slicing of a sample into ~5μm sections, followed by staining and imaging. However, this approach has several limitations: it results in a biased molecular readout by undersampling the true biological volume, loses spatial information for connected structures such as vasculature, neuronal connections, or airways, and may miss cell-cell interactions unless the interacting cells happen to lie within the same 5μm z-plane. These limitations can lead to incomplete or even misleading interpretations of tissue structure and function.

To address these limitations, a new field—‘3D histology’—has emerged. This technique aims to stain and image deep tissue volumes intact, without serial sectioning, allowing for an unbiased and comprehensive view of biological tissues and systems.

Oncology diagnosis

Traditionally, tumor biopsies have been studied and diagnosed using conventional two-dimensional (2D) histopathology. However, this approach significantly undersamples tumor volume, which is problematic given the well-known feature of intratumoral heterogeneity in cancers. A cell count derived from such a small portion of the tumor may not accurately reflect the true cellular composition. Moreover, important 3D structures, such as vasculature or collagen fibers, are more easily visualized in 3D, yet are easy to miss or underestimate in 2D sections. These structures may correlate with clinicopathological features and play a role in prognosis prediction or disease subtype stratification for treatment decisions. Therefore, the development of 3D histology techniques is essential to enable more accurate and comprehensive profiling of tumor architecture, which in turn supports improved patient outcomes in oncology.

Neuroscience research

The brain is a highly organized, complex, three-dimensional structure, comprised of detailed, interacting networks of neurons, blood vessels and glial cells. A comphrenesive approach to studying the brain is necessary to obtain a holisitic understanding of these interacting components in their native context. Therefore, development of 3D-histology methods to study the brain is highly valuable to understand the molecular changes associated with certain physiological and pathological states.