Dario Alessi - SCILLS - The Scottish Institute for Cell Signalling

Professor Dario Alessi

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Professor Dario Alessi FRS, FRSE - Honorary Programme Leader

Background

Dario Alessi was born in France, attended high school in Brussels and obtained a BSc in Biochemistry from the University of Birmingham, UK in 1988. He received a Ph.D. in 1991 for work on the synthesis and use of spin-labelled ATP analogues to study muscle contraction under the joint supervision of Ian Trayer (University of Birmingham) and David Trentham FRS (National Institute of Medical Research, Mill Hill, London). He then carried out postdoctoral research with Sir Philip Cohen FRS in the MRC Protein Phosphorylation Unit at Dundee from 1991 to 1996, where he became fascinated by protein kinases and how they are regulated by insulin, growth factors and other extracellular signals that control almost all aspects of cell biology.

In 1997 Dario became a Programme Leader in the MRC Protein Phosphorylation Unit, where he has worked ever since. A key focus of his current research is to understand the regulation and physiological roles of key protein kinases that implicated in human disease and to exploit findings emerging from these studies to develop novel treatments for disease.

Selected career achievements:

1. Identified ERK1 and ERK2 as the physiological substrates of the dual specificity protein phosphatase CL100/MKP1 (1993).
2. Described the mechanism by which PKB/Akt is activated by phosphorylation at Thr308 and Ser473 (1996).
3. Discovered and characterised PDK1, the protein kinase that phosphorylates PKB/Akt at Thr308 (1997)
4. Worked out how PDK1 was regulated and showed that it activates 20 other protein kinases of the AGC subfamily (1998-2002).
5. Discovered MSK1 and MSK2, two protein kinases that are activated by mitogen and stress-activated signalling pathways (1998).
6. Discovered that the LKB1 tumour suppressor protein kinase exists in a complex with the pseudokinase STRAD and MO25 (2003).
7. Discovered that LKB1 phosphorylates and activates AMPK and 12 other protein kinases related to AMPK (2003-2004).
8. Demonstrated that reducing the expression of PDK1 in mice prevents cancer development in PTEN+/- mice, validating PDK1 as an anti-cancer drug target (2005).
9. Identified the protein kinases SPAK/OSR1 as physiological substrates of the protein kinases WNK1 and WNK4 protein kinases that are mutated in Gordon’s hypertension syndrome (2005).
10. Showed that SPAK/OSR1 regulate blood pressure by controlling the activity of the NCC and NKCC2 ion co-transporters (2007-2008).
11. Identified the ERM proteins as the first potential substrates for LRRK2, a protein kinase whose mutation predisposes to Parkinson’s disease, and exploited this finding to develop the first robust assay for this enzyme (2007).
12. Demonstrated that small molecule activators of AMPK suppress PTEN-mediated tumourigenesis in mice (2008).
13. Demonstrated that some protein kinases related to AMPK are controlled by an unusual polyubiquitination reaction I which the polyubiquitin chains are linked via Lys29/Lys33 of ubiquitin (2008).

Awards and Honours

1999 Colworth Medal of the Biochemical Society
2000 The Eppendorf Young European Investigator Award
2002 Elected a Fellow of the Royal Society of Edinburgh
2002 Morgagni Young Investigator Prize
2002 Royal Society of Edinburgh Makdougall Brisbane Prize
2002 Philip Leverhulme Prize
2003 FEBS Anniversary Prize of the Gesellschaft für Biochemie und Molekularbiologie
2004 RD Lawrence Lecture of Diabetes UK
2005 Elected a Member of EMBO
2005 Awarded the EMBO Gold Medal
2006 Francis Crick Prize Lecture of The Royal Society
2008 Elected a Fellow of The Royal Society