1970 …2024

Tutkimustuotoksia vuodessa

Henkilökohtainen profiili

Tutkimuksen ja opetuksen kuvaus

Leukocyte Adhesion

Most leukocyte functions involve adhesion to other cells or extracellular molecules. Leukocyte adhesion needs members of different molecular families, but the most important are the leukocyte integrins (β2-integrins) and their cellular ligands, the intercellular adhesion molecules (ICAM).

The β2-integrin family is composed of four members with a common β2-chain. αLβ2 (LFA-1, CD11a/CD18) is primarily expressed on lymphocytes, αMβ2 (MAC-1, CD11b/CD18) on granulocytes and αXβ2 and αDβ2 on monocytes and macrophages. ICAM-1 is widely expressed and its expression often up-regulated, ICAM-2 is found in leukocytes and endothelial cells, ICAM-3 in leukocytes, ICAM-4 in red cells and ICAM-5 in neurons.

Currently, most work is focussed on: 1) the structures of these molecules and the regulation of integrin activity by phosphorylation, 2) the regulation of neurite growth and differentiation. The phosphorylation sites have been mapped and site-specific antisera have been prepared. Both intracellular and extracellular interactions are studied in detail (see PowerPoint presentation made by S. Marchesan). Furthermore, we are making reagents, which affect adhesion and these may have therapeutic value.

Our group has an extensive know-how in modern biochemistry, molecular biology and cell biology and cooperates with several internationally recognized research groups. In addition, several foreign graduate students, postdoctoral fellows and senior scientists have worked in the group and are currently members of the research effort.

Ansioluettelo

Born in Helsinki, Finland, December 1, 1942
M.D., University of Helsinki, 1968
Doctor of Medical Sciences, University of Helsinki, 1971
Docent in Cell Biology, 1974, University of Helsinki
Professor of Biochemistry, Åbo Akademi University 1979-1981
Professor and Chairman, Department of Biochemistry, University of Helsinki, 1981-
Research Professor of the Academy of Finland, 1986-1991
Postdoctoral fellow, University of Washington, 1972-1974 (S. Hakomo­ri)
Visiting professor, La Jolla Cancer Research Foundation, 1988-1989 (E. Ruoslahti)
Organized and co-organized a number of international conferences
More than 150 international lectures at congresses and foreign universities
The Finnish representative in FEBS (Federation of European Biochemical Societies) 1986-1996, and in IUBMB (International Union of Biochemistry and Molecular Biology) 1987-1996
Nordic Committee on Biochemistry 1984-1996
Permanent secretary at the Finnish Society of Sciences and Letters 1992-
Finnish delegate in the International Council of Scientific Unions 1993-98
Vice-chairman of the Delegation of the Finnish Academies of Science 1992-98
Chairman of the organizing committee of the Science Days in Finland 2001
Chairman of the grant committee of the Finnish Medical Association (Finska Läkaresällskapet) 1996-99
Chairman of the Finnish Medical Association 2000-2001
Cited more than 13.000 times, which is one of the highest numbers for Finnish scientists in the natural sciences. The current h-index is 64

Memberships in scientific academies

European Molecular Biology Organization (EMBO) 1980-. Member of its Council
(1986-91)
Finnish Academy of Sciences 1982-
Finnish Society of Sciences and Letters, 1983-
World Cultural Council 1984-. Founding member. Total 124 including 25 Nobel laureates
Academia Europaea 1989-
World Innovation Foundation. Honorary member 2003
The Royal Swedish Academy of Sciences,  2007-
The Royal Society of Arts and Sciences in Göteborg, 2008-
Appointed by Karolinska institutet to evaluate the Macchiarini-case, 2016

Major scientific achievements

Showed first that viral membrane proteins have a hydrophobic anchor (1972)
Developed the first method for specific radioactive labeling of cell surface carbohydrates (1973)
One of those that first found the adhesive glycoprotein fibronectin (1973)
Developed a method for specific labeling of cell surface sialic acids (1977)
Made the first detailed studies on the biosynthesis and gly­cosylation of a mammalian membra­ne protein (glycophorin A) (1979 - 1985)
Showed that the K562 cell line is erythroid and that it can be induced to red cell differentiation. This was the first human cell line described showing erythroid characteris­tics
First identified, simultaneously with Moore, the Rho(D) protein (1982-83)
Identified and characterized several important leukocyte surface glycoproteins (1976‑) Such are CD43, CD45 and the leukocyte integrins
Identified leukocyte proteins as adhesion molecules (1985)
Identified the adhesion molecule ICAM-1, simultaneously with Springer’s group (1987)
Identified functionally important cell surface glycoproteins in natural killer cells (1988-)
Found the first activating peptide for leukocyte integrins (1993-95)
Characterized two new intercellular adhesion molecules, ICAM-4 and ICAM-5 (1995-)
Explained why cell surface proteins are glycoproteins (1996)
Detailed studies on integrin phosphorylation (1991-)
Established that an ICAM-molecule shows homophilic interaction in brain (2000)
Found an association between leukocyte integrins and metalloproteases. Described a low m.w. inhibitor of   this phenomenon  (2003-04)
Discovery of the first endogenous inhibitor of leukocyte adhesion (cowork with T. Chavakis et al. 2008)
Showed that stimulation of glutamate receptors activates metalloproteases resulting in cleavage of ICAM-5
Suppression by ICAM-5 of T cell activation (2007,2008)
Showed that β2-integrin phosporylation affects binding of cytosceletalproteins (2008)
Identified Tiam1 as an important molecule in β2-integrin signalling (2011)
Determined the 3-dimensional strucuture of domains 1-4 of ICAM-5 (2014) (co-work with J.M. Casasnovas
Showed that β2-integrins signal to β1-integrins by phosphorylation(2014)

Prizes and honours

The Komppa award for the best thesis in chemistry in Finland (1971)
The Scandinavian Anders Jahre Prize in Medicine, University of Oslo (1981)
The 150-year Anniversary Prize of the Finnish Medical Association (1985)
Knight of the Finnish White Rose (1988)
Professor of the Year in Finland (1995) (all fields included)
The Äyräpää Prize of the Finnish Medical Association Duodecim (1997).
The silver medal of the Finnish Society of Science and Letters (2002)
The silver medal of the University of Helsinki (2002)
Commander of the Order of the Finnish Lion (2002)
Chevalier de l’Ordre des Palmes Académique, France (2009)
J.W. Runeberg Prize in Medicine (2010)
Honorary member of the Finnish Medical Association (2010)
 Commander of the order of the Finnish White Rose (2012)
One of Finlands 100 most prominent scientists throuout time (2014)

Ph.D. dissertations supervised in the group

1. Mikko Jokinen, 1982. With distinction (laudatur). Primus of the Faculty of Science
2. Kimmo Karhi, 1983
3. Marja Ekblom, 1985. Together with Leif C. Andersson
4. Heli Suomalainen, 1986. Together with Jim Schröder and Leif  C. Andersson
5. Anja Lampio, 1988
6. Pekka Nortamo, 1993
7. Kristiina Somersalo, 1995. With Tuomo Timonen
8. Rosalba Salcedo, 1996. With Manuel Patarroyo
9. Rui Li, 1996. With distinction (laudatur)
10. Matti Autero, 1996
11. Leena Valmu, 1999
12. Li Tian, 2001. With distinction (laudatur)
13. Susanna Fagerholm, 2002
14. Tiina Hilden, 2005. With distinction (laudatur)
15. Michael Stefanidakis, 2006. With Erkki Koivunen
16. Susanna Nurmi, 2008
17.Henrietta Nyman-Huttunen, 2011
18.Lin Ning, 2013
19. Liisa Uotila, 2014

 

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  • 311 Peruslääketieteet

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