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Uhlén Lab - Karolinska Institutet


Our research group is studying cancer and developmental related processes in various tissues. The biological platforms that we are applying are clinical tumor samples, tissue slices, primary cell cultures, cell lines, and stem cells. To study intratumoral heterogeneity, cancer stem cells, epithelial-mesenchymal transition (EMT), cell division, cell differentiation, and migration/networking we are applying state-of-the-art imaging techniques and modern genetic tools. Our focus is to shed light on the intracellular cell signaling mechanisms that have an impact on cancer and development. We are developing new tissue preparation protocols and imaging methods that can visualise tumors and tissues in three dimensions (3D).

Tumor visualisation

Intratumoral heterogeneity is a critical factor when diagnosing and treating patients with cancer. Marked differences in the genetic and epigenetic backgrounds of cancer cells have been revealed by advances in genome sequencing, yet little is known about the phenotypic landscape and the spatial distribution of intratumoral heterogeneity within solid tumours. Here, we show that three-dimensional light-sheet microscopy of cleared solid tumours can identify unique patterns of phenotypic heterogene- ity, in the epithelial-to-mesenchymal transition and in angiogenesis, at single-cell resolution in whole formalin-fixed paraffin- embedded (FFPE) biopsy samples. We also show that cleared FFPE samples can be re-embedded in paraffin after examination for future use, and that our tumour-phenotyping pipeline can determine tumour stage and stratify patient prognosis from clinical samples with higher accuracy than current diagnostic methods, thus facilitating the design of more efficient cancer therapies.

Calcium signaling

Calcium is an almost universal intracellular messenger that controls a vast number of cellular processes spanning from fertilization to cell death. Cells create large calcium concentration gradients (~10'000 to 1) between the extracellular fluid, cytoplasm, and internal calcium stores by means of calcium-pumps located in the plasma membrane and in the membranes of internal calcium stores. These gradients provide ideal conditions for the use of calcium as a cellular currency that supports the propagation of intracellular calcium waves. The concerted actions of calcium transporters located in the plasma membrane and in the membranes surrounding internal stores, including the endoplasmic and sarcoplasmic reticulum, the mitochondria, and the nucleus, can generate calcium oscillations. As with a radio transmitter, cells exploit the two key features of oscillatory signals - frequency and amplitude - to utilize calcium as a second messenger to generate a large variety of intracellular signals. This is an efficient way to use the same second messenger to activate many different cell processes.

The Lab

The lab is located on the 6th floor of the Biomedicum research building at the Karolinska Institutet's north campus in Solna. To study tissue samples we are applying various imaging techniques, such as fluorescence microscopy, confocal microscopy, 2-photon laser scanning microscopy, and light-sheet microscopy. All imaging setups are available in our laboratory. The unit is well-equipped in a highly vibrant research community with substantial resources and excellent core facilities.

[ Department of Medical Biochemistry and Biophysics | Karolinska Institutet ]
Updated: April, 2022