Mathias Uhlén
Research interests
Mathias Uhlen research has resulted in more than 800 peer-reviewed publications leading to more than 100,000 academic citations with an h-index of 144 (Google Scholar). He has supervised more than 100 graduate students to PhD-exam. He has co-founded more than 20 start-up companies based on his research, including publicly listed companies Biotage (Sweden) and Abclon (South Korea). His focus in science has been technology- and data-driven research, involving protein science, antibody engineering, systems biology and precision medicine. Examples of major achievements are:
- Next generation DNA sequencing.
The concept of real time sequencing by synthesis is today used in all major “next generation sequencing” systems and it has led to hundreds of thousand publications in the last decade. This concept involves the detecting of the incorporation of nucleotides in real-time during synthesis by a DNA polymerase. The concept, first described in 1993 (1) depends on several important underlying technologies, including attachment of DNA to solid supports, the use of engineered polymerases for synthesis of a complementary nucleotide and the detection of the incorporated nucleotide in real-time to generate sequencing. This concept (2) was successfully used in the first massive parallel sequencing instrument (454) launched in 2005 (3) and this scientific break-through was later followed by alternative technology platforms, often based on fluorescent detection (4).
2. The Human Protein Atlas
The Human Protein Atlas (www.proteinatlas.org) program started in 2003 with the aim to contribute to the holistic understanding of all the proteins encoded from our DNA. The objective of the program, funded by the Knut and Alice Wallenberg Foundation, is to map all the human proteins in cells, tissues, organs and blood using integration of various omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics, and AI-based systems biology. The ultimate aim for the project is a complete understanding of the functions and interactions of all proteins. During the first 20 years, the open access resource has launched more than 5 million web pages with 10 million high-resolution microscope images, to allow individual researchers both in industry and academia to explore the proteome space across the human body (5,6,7). The Tissue Atlas paper published in Science in 2015 (5) is one of the most cited publications from Europe in the last 10 years.
3. The national infrastructure SciLifeLab
Dr Uhlen was the Founding Director of the Science for Life Laboratory initiated with support from the Swedish government in 2010 (8). This national infrastructure, originally in Stockholm and Uppsala, was launched to allow technology- and data-driven research in life science. The number of researchers has grown to more than thousand at the Stockholm site, with collaborations across all universities in Sweden Many thousands of projects are executed annually, spanning many research fields, such as genomics, proteomics, structural biology, planetary biology, data-driven life science, drug development and precision medicine. Many projects in data-drive life science are supported by the non-profit Knut and Alice Wallenberg Foundation.
4. Affinity-based protein engineering
This broad concept was developed to use specific binding of proteins (affinity) in combination with protein engineering and it has led to many successful applications widely used in the life science community. This includes engineered protein A (9) and protein G for purification of antibodies, affinity tags for purification of recombinant fusion proteins,(10), clinically validated protein scaffold binders, such as Affibodies (11), solid phase methods for DNA handling (12) and alkali-stable matrix for purification of antibodies, such as MabSelect SuRe. This latter platform has been used for the manufacturing of the majority of therapeutic antibodies on the market today.
5. Precision medicine
Several analytical platforms have been developed to allow the determination of protein profiles from a small drop of blood. Quantitative data was obtained using mass spectrometry-based technology as well as antibody-based proximity extension assays. The concept has been used to generate an open access Human Blood resource (13) covering tens of thousands of patients having various diagnosis, such as cancer, autoimmune, neurodegenerative, infectious and cardiovascular disease, respectively. The platform has also been used to study wellness and age/sex-related changes in blood profiles (14).
See full publication lists on Google Scholar or ORCID.
Group members
- Åsa Sievertzon, scientist
- Evelina Sjöstedt, scientist
- Kalle von Felitzen, bioinformatics
- Per Oksvold, bioinformatics
- Mattias Forsberg, bioinformatics
- Martin Zwahlen, bioinformatics
- Fredric Johansson, bioinfomatics
- Maria Bueno Alvez, graduate student