Harm KampingaParticipant CVON-DOSIS

Brief summary of research over the last five years

The focus of my research group concerns the regulation of protein quality control (PQC). My research group try to understand how heat shock proteins are regulated to protect cells against acute proteotoxic stress as well as chronic forms of stress, exploring the discovery that HSP families are large families that likely evolved to guarantee specificity and carry out multiple PQC functions. My laboratory generated a large, regulatable expression library of both human and Drosophila HSPs to test if and how they can modulate a variety (age-related) protein folding diseases including several neurodegenerative diseases and cardiac diseases (atrial fibrillation and cardiomyopathies). We have also embarked on studies on the mechanisms by which certain mutations in HSPs cause disease, including cardiac diseases, and how other components within the HSP network might compensate for the defects associated with these mutations. In the CVON project, our insights are exploited to uncover if and how stimulation of the PQC network may compensate for increased frailty of sarcomeric components associated with gene mutations that cause inherited cardiomyopathies.

 


 

Current Positions

Since 2015 Head of the Department of Cell Biology, UMCG, Groningen

Since 2001 Full Professor at the Department of Cell Biology, UMCG, Groningen

 


 

Top 5 recent publications

1. Minoia M, Boncoraglio A, Vinet J, Morelli F, Brunsting JF, Poletti A, Krom S, Reits E, Kampinga HH, Carra S‡. BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta: implication for a proteasome-to-autophagy switch. Autophagy, 10 (2014) 1603-1621 (‡ = shared last authors). (IPF = 11.8)

2. Smeet CJLM, Jezierska J, Watanabe H, Duarri A, Fokkens MR, Meijer M, Zhou Q, Yakovleva, T, Boddeke E, den Dunnen W, van Deursen J, Bakalkin G, Kampinga HH, van de Sluis B, Verbeek DS. Elevated mutant dynorphin A causes Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type 23. Brain 138 (2015) 2537-2552. (IPF = 10.1)

3. Vos MJ, Carra S, Kanon B, Bosveld F, Klauke K, Sibon OCM* and Kampinga HH* (*shared last authors). Specific protein homeostatic functions of small heat shock proteins increase lifespan. Ageing Cell 15 (2016) 217-226. (IPF = 6.3)

4. Kakkar V, Månsson C, de Mattos EP, Bergink S, van der Zwaag M, van Waarde MAWH, Kloosterhuis NJ, Melki R, van Cruchten R, Al-Karadaghi S, Arosio P, Dobson CM, Knowles TPJ, Bates GP, van Deursen J, Linse S, van de Sluis AJ, Emanuelsson C*, and Kampinga HH*. (*shared last authors). The S/T-rich motif in the DNAJB6 chaperone delays polyglutamine aggregation and the onset of disease in a mouse model. Molecular Cell, 2016, 62 (2016) 1-12. (IPF = 14.0)

5. Kampinga HH, Bergink S. Heat shock proteins as potential targets for protective strategies in neurodegeneration. Lancet Neurology, 2016, 15:748-759 (IPF = 21.9)

 


 

Selection of ongoing projects

2015  Cardiovasculair Onderzoek Nederland (CVON) research grant. Determinants of susceptibility in inherited cardiomyopathy: towards novel therapeutic approaches. Acronym: Dosis. Coordinators: Jolanda van der Velden (VUMC) & Rudolf de Boer (UMCG). National consortium grant.

2015  ALW Open Programme – Long term DNA damage, protein homeostasis and neurodegeneration. With Steven Bergink (UMCG)

2014  Dutch Heart Foundation (NHS- Hartedroom) – Boosting chaperone networks to counteract juvenile DCM caused by chaperone mutations. With Bianca Brundel (VUMC), Jolanda van der Velden (VUMC), Michels Vos (Isela Clinic Zwolle)

2012  Science without Borders (Brazil) – Identification of intrinsic genetic modifiers of Machado-Joseph disease: focus on molecular chaperones. With Laura Bannach and Maria Luiza Pereira (Porto Alegre, Brazil)