Uhlén Lab - Karolinska Institutet
Research
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.
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