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Mathias Uhlén

Dr. Mathias Uhlén, Professor of Microbiology

Mathias Uhlén

KTH School of Engineering Sciences in Chemistry, Biotechnology and Health
Department of Protein Science
Division of Systems Biology
KTH Royal Institute of Technology (CBH School)
106 91 Stockholm, Sweden
Email: mathiasu@kth.se
Direct phone: +46 70 513 2101

CV (pdf 205 kB)

Biography

Mathias Uhlén received his PhD at the Royal Institute of Technology (KTH) , Stockholm, Sweden in 1984. After a post-doc period at the EMBL  in Heidelberg, Germany, he became professor in microbiology at KTH in 1988.

His research is focused on protein science , antibody engineering  engineering and precision medicine  and range from basic research in human and microbial biology to more applied research, including clinical applications in cancer, infectious diseases, cardiovascular diseases, autoimmune diseases and neurobiology. His research has resulted in more than 750  publications.

He is member of several academies and societies, including Royal Swedish Academy of Science , National Academy of Engineering (USA) , the Swedish Academy of Engineering Science (IVA)  and the European Molecular Biology Organization (EMBO) .

His group was the first to describe a number of innovations in science including:

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 (A) engineered protein A (1) and protein G for purification of antibodies, (B) affinity tags (2) for purification of recombinant fusion proteins, (C) Affibodies (3) – clinically validated protein scaffold binders, (D) the first solid phase methods for DNA handling using the biotin-streptavidin system (4,5,6) and (E) MabSelect SuRe – alkali-stable matrix for purification of antibodies. This ligand has been used for the manufacturing of the majority of therapeutic antibodies on the market today.

Real-time sequencing by synthesis. This concept involves the detecting of the incorporation of nucleotides in real-time during synthesis by a DNA polymerase and to use this for DNA sequencing. The concept, first described in 1993 (7), 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 was used by the Pyrosequencing (8) method leading to the first massive parallel sequencing instrument (454). The concept of real time sequencing by synthesis is now used in all major “next generation sequencing” systems and it has been used to generate sequences used in hundreds of thousand publications in the last decade.

Map of the human proteome.  The Human Protein Atlas  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 is to map all the human proteins in cells, tissues, and organs using integration of various omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics, and systems biology. The ultimate aim for the project is a complete understanding of the functions and interactions of all proteins and where in the different cells and tissues they reside. 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. The resource consists of various sections, spanning from tissues (9), brain (10), immune cells (11), blood proteins, diseases and structures. The Tissue Atlas paper (9) is one of the most cited publications from Europe in the last 10 years.

Science for Life Laboratory (SciLifeLab)

Dr Uhlén was the Founding Director of the SciLifeLab  from 2010–2015. This national infrastructure was launched in Stockholm with funding from the Swedish government to allow technology- and data-driven research to be establish as a support for Swedish and European research in life science. From 2013, the infrastructure was merged with a similar center in Uppsala and the number of researchers has grown to more than thousand only at the Stockholm site. 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.

Career

1979 M.Sc. in Chemical Engineering, KTH , Stockholm, Sweden
1984 Ph.D. Dept. of Biotechnology, KTH, Stockholm, Sweden
1985–86 Post-doc, EMBL , Heidelberg, Germany
1988– Full professor in Biotechnology, KTH, Stockholm, Sweden
1999–2001 Vice-President KTH, responsible for external relations
2003– Director of the Human Protein Atlas (HPA)  program
2010–2015 Founding Director, Science for Life Laboratory (SciLifeLab)
2012–2020 Professor (20 percent), Danish Technical University (DTU) , Denmark
2019– Guest professor (25 percent) at Karolinska Institutet
2019– Member of the Board of Directors for the Swedish Research Council

Recognition

Bibliometry

  • Number of publications in total: 750
  • Number of total citations: 95,000 citations
  • Number of citations last year (2022): 10,000
  • H-index: 136

(Statistics according to Google Scholar, March 2023)

Relevant links

Entrepeneurial achievements (selected)

More than 70 international patent applications. Founders of 20 start-up companies and former member of several Board of Directors, including public companies such as Bure (Sweden), Biotage (Sweden), Alligator Bioscience (Sweden), Novozymes (Denmark), Nordiag (Norway) and Amersham (UK). Vice-President KTH (1999–2001) responsible for external relations.

Key (own) references

  1. Uhlen et al ”Complete sequence of the staphylococcal gene encoding protein A. A gene evolved through multiple duplications” J Biol Chem 259 (3):1695–702 (1984)
  2. Löwenadler et al “Production of specific antibodies against protein A fusion proteins.” EMBO J 5 (9): 2393–8 (1986)
  3. Nord et al “Binding proteins selected from combinatorial libraries of an alpha-helical bacterial receptor domain” Nature Biotechn. 15 (8): 772–8 (1997)
  4. Ståhl et al “Solid-phase sequencing using the biotin-avidin system” Nucl. Acids Res. 16: 3025–3038 (1988)
  5. Hultman et al “Direct solid phase sequencing of genomic and plasmid DNA using magnetic beads as solid support” Nucl. Acids Res. 17: 4937–4946 (1989)
  6. Uhlen “Magnetic separation of DNA” Nature 31;340(6236):733-4 (1989)
  7. Nyrén et al “Solid phase DNA mini-sequencing by an enzymatic luminometric inorganic pyrophosphate detection assay” Anal. Biochem. 208: 171–175 (1993)
  8. Ronaghi et al “A sequencing method based on real-time pyrophosphate” Science 281: 363–365 (1998)
  9. Uhlen et al (2015) “Tissue-based map of the human proteome” Science 347: 126041
  10. Uhlen et al (2019) “A genome-wide transcriptomic analysis of protein-coding genes in human blood cells” Science366 (6472): eann9198
  11. Sjöstedt et al (2020) “An atlas of the human, pig and mouse brain” Science 367 eaay5947

See full publication lists on Google Scholar , Web of Science  or ORCID .

Publications