Research Groups

Kampinga group

A healthy proteome in cells is not only crucial for functionality of cells, but also essential for preventing damage (protein aggregates) that lead to a cascade of toxic events that threaten cellular health span. To ensure a proper protein homeostasis, an intricate protein quality control (PQC) network exists in cells in which Heat Shock Proteins (HSP), the central research topic in my group, play a central role.

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  • Harm Kampinga Visit
    Position

    Head Department; Principal Investigator

    Research fields

    Regulation of Function of Heat Shock Proteins

    PhD Students
    Technicians
      • Selected Publications:
      1. Rujano MA, Bosveld A, Salomons FA, Dijk F, van Waarde MAWH, van der Want JJL, de Vos RAI, Brunt ER, Sibon OCM, Kampinga HH. 2006. Polarized asymmetric inheritance of accumulated protein damage in higher eukaryotes. PloS Biology 4, 2325-2335. (pdf)
      2. Hageman J, Rujano MA, van Waarde MAWH, Kakkar V, Dirks D, Govorukhina N, Oosterveld-Hut HJM, Lubsen NH, Kampinga HH. 2010. A DNAJB Chaperone Subfamily with HDAC-dependent Activities Suppresses Toxic Protein Aggregation. Molecular Cell 37, 355-369. (pdf)
      3. Kampinga HH, Craig EA. 2010 The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nature Reviews Mol. Cell. Biol. 11, 579-592. (pdf)
      4. Vos MJ, Zijlstra MP, Kanon B, van Waarde-Verhagen MAWH, Brunt ERP, Oosterveld-Hut HMJ, Carra S, Sibon OCM, Kampinga HH. 2010. HSPB7 is the most potent polyQ aggregation suppressor within the HSPB family of molecular chaperones. Human Molecular Genetics 19, 4677-4693. (pdf)
      5. Carra S, Boncoraglio A, Bart Kanon, Brunsting JF, Minoia M, Rana A, Vos MJ, Seidel K, Sibon OCM, Kampinga HH. 2010. Identification of the Drosophila ortholog of HSPB8: implication of HSPB8 loss of function in protein folding diseases. J Biol Chem. 285, 37811-37822. (pdf)
      6. Minoia M, Boncoraglio A, Vinet J, Morelli F, Brunsting JF, Poletti A, Krom S, Reits E, Kampinga HH, Carra S‡. 2014. BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta: implication for a proteasome-to-autophagy switch. Autophagy, 10, 1603-1621 (‡ = shared last authors). (pdf)
      7. Mansson C, Arosio P, Hussein R, Kampinga HH, Hashem RM, Boelens WC, Dobson CM, Knowles TPJ, Linse S, Emanuelsson C. 2014. Interaction of the molecular chaperone DNAJB6 with growing amyloid-beta 42 (Aβ42) aggregates leads to sub-stoichiometric inhibition of amyloid formation. Biol. Chem. 289, 31066-31076. (pdf)
      8. Vos MJ, Carra S, Kanon B, Bosveld F, Klauke K, Sibon OCM* and Kampinga HH* 2016. Specific protein homeostatic functions of small heat shock proteins increase lifespan. Ageing Cell 15, 217-226. (*shared last authors). (pdf)
      9. 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*. 2016. The S/T-rich motif in the DNAJB6 chaperone delays polyglutamine aggregation and the onset of disease in a mouse model. Molecular Cell 62, 1-12. (*shared last authors). (pdf)
      10. Kampinga HH, Bergink S. 2016. Heat shock proteins as potential targets for protective strategies in neurodegeneration. Lancet Neurology, doi: 10.1016/S1474-4422(16)00099-5. (pdf)
  • PhD students:

    2014 Kakkar,V. (Vaishali)
    2014 Minoia,M. (Melania)
    2013 Rembacz,K.P. (Krzysztof)
    2012 Yang,J. (Jing)
    2012 Ke,L. (Lei)
    2011 Zijlstra,M.P. (Marianne)
    2011 Seidel,K. (Kay)
    2009 Vos,M.J. (Michel)
    2009 Nováková,A. (Alena)
    2008 Hageman,J. (Jurre)
    2008 Bosveld,F. (Floris)
    2007 Yi,X. (Xia)
    2007 Rujano Maldonado,M.A. (Maria)
    2006 Vries,H.I. de (Hilda)
    2005 Hut,H.M.J. (Hendrika)
  • Harm Kampinga graduated in Biology at the University of Groningen in 1984 and received my PhD in 1989 in Groningen. After being assistant – and associated professor in Radiation Oncology, he became full professor in the Department of Cell Biology in 2001 and became head of this Department in 2015.

    The central theme of his research has always been related to the consequences of protein un- or misfolding on cellular functions. Initially, his work was centered around the biological effects of heat shock on cells in relation to the use of hyperthermia in combination with radiation or/and chemotherapy in cancer treatments. During these studies, Kampinga became interested in Heat Shock Proteins (HSP) that could protect cells from the cell biological effects of heat shock and focused my research on the functional regulation and diversity HSPs.

    Kampinga’ s lab was the first to clone a majority of all human and Drosophila HSPs and subsequently screened them for activity in several (age-related) cell and drosophila models for neurodegenerative diseases (in particular CAG repeat expansion diseases) and cardiac diseases. Major discoveries from his lab include the asymmetric segregation of protein damage in stem cells, the functional diversity of HSPs and their role in dealing with different disease-associated protein aggregation diseases, and the discovery of set of specific DNAJ family protein members (DNAJB6 and DNAJB8) with an exquisitely high potency to delay amyloidogenesis.

  • See dissertations supervised by Harm H. Kampinga (promotor)

     

    DNAJ proteins: more than just “co-chaperones”
    2014, Kakkar,V. (Vaishali)
    BCN-BRAIN / MOLAR: Molecular Neuroscience and Ageing Research

    In order to be biologically active, every nascent polypeptide emerging from the ribosomes should fold and acquire its native conformation. Non-native conformations lead to drastic events ranging from compromised biological activity of the protein to its tendency to (self)aggregate or inappropriately interact with cellular components. Heat Shock Proteins (HSP) act as molecula…

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    Chaperones, protein homeostasis & protein aggregation diseases
    2014, Minoia,M. (Melania)
    BCN-BRAIN / MOLAR: Molecular Neuroscience and Ageing Research

    Proteins are the functional molecules of cells and have to be folded into a specific three-dimensional structure. Besides being non-functional, non-folded proteins can easily clump together and form aggregates that can cause disease (e.g. Parkinson’s disease and Huntington’s disease). To avoid this, cells contain special sets of proteins called Heat Shock Proteins (HSPs)…

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    The functional relationship between peroxisomes, bile salts and lipid rafts in the liver
    2013, Rembacz,K.P. (Krzysztof)
    GUIDE / CLDM: Center for Liver, Digestive and Metabolic Diseases

    The liver is a central organ in regulating body homeostasis. It controls body temperature, protein, glucose and fat metabolism as well as the removal of toxic (waste) products. It plays an integrative function in the whole organism by cooperation with the circular and digestive system. This feature of the liver allows for the effective exchange of nutrients between every c…

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    Autophagy, FOXO1 and proteostasis : implications for human diseases
    2012, Yang,J. (Jing)
    BCN-BRAIN

    Autophagy is a tightly regulated process in cells to remove dysfunctional or damaged cellular components before they become harmful. Deregulation of autophagy is implicated in diseases like cancer or neurodegeneration. In this thesis, we show that the longevity-associated transcription factor FOXO1 can increase autophagy. Intriguingly, this occurs independent from its trans…

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    Molecular remodeling in atrial fibrillation: protective roles of small HSPs
    2012, Ke,L. (Lei)
    GUIDE / CVC: CardioVascular Centre

    Atrial Fibrillation (AF), the most common sustained arrhythmia, is associated with substantial cardiovascular morbidity and mortality. AF has the tendency to become more persistent over time. Recently, an increased awareness of the role of “atrial remodeling” has advanced our understanding of the persistency of AF. The concept “atrial remodeling” defines any changes …

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    The role of heat shock proteins in polyQ disorders
    2011, Zijlstra,M.P. (Marianne)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Abstract: The polyglutamine (polyQ) disorders are diseases of the central nervous system, caused by a CAG triplet expansion in the affected genes, leading to protein aggregation and inclusion formation of the mutant protein in neurons. The size of the expanded CAG repeat correlates with the age at disease onset, yet, up to 50% of the variation in age of onset is determi…

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    Neurogenerative diseases and the Protein quality control system
    2011, Seidel,K. (Kay)
    BCN-BRAIN

    ABSTRACT: With increasing life-expectancy in the western world, diseases of old age are becoming more prevalent, in particular the neurodegenerative diseases. Here, certain components of the brain and spinal cord degenerate progressively. The symptoms are grave and have a severe impact on the patient’s lifespan and quality of life. Some of these diseases occur sporadic…

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    Small heat shock proteins: Implications for neurodegeneration & longevity
    2009, Vos,M.J. (Michel)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Aging in general, as well as several age-related diseases, are characterized by a gradual decrease in proper cell functioning. Cells continuously have to deal with protein renewal, degradation and folding. The main hazard of these processes is the formation of partly- or incorrectly folded proteins which tend to form toxic aggregates and disturb cellular functions. Fortuna…

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    New considerations in predicting toxicity from partial irradiation of the lung
    2009, Nováková,A. (Alena)

    New considerations in predicting toxicity from partial irradiation of the lung / Alena Novâakovâa. – [S.l. : s.n.], cop. 2009 (Groningen : Van Denderen). – 194 p. : ill. ; 24 cm Proefschrift Rijksuniversiteit Groningen. – Met lit.opg. en samenvatting in het Nederlands. ISBN 978-90-367-3868-2

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    The human HSP70/HSP40 chaperone family : a study on its capacity to combat proteotoxic stress
    2008, Hageman,J. (Jurre)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    All cells are constantly threatened by both physical and chemical stress factors that can damage e.g. the DNA and proteins. Whereas the molecular mechanisms responsible for DNA repair have been studied in great detail, the mechanism underlying the repair and disposal of damaged proteins are far less investigated and less understood. It is well known that DNA damage in co…

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    Physiological implications of impaired de novo Coenzyme A Biosynthesis in Drosophila melanogaster
    2008, Bosveld,F. (Floris)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Coenzyme A constitutes an essential cofactor whose biosynthesis route is conserved amongst species. De novo CoA is synthesized from pantothenate by the subsequent action of five enzymes; PANK, PPCS, PPCDC, PPAT and DPCK. Although CoA biosynthesis is conserved, significant dissimilarities exist between the eukaryotic and bacterial enzymes, which makes these enzymes potential …

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    The impact of impaired DNA damage responses on cells, tissues and organisms
    2007, Yi,X. (Xia)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Current cancer therapies rely mainly on DNA damaging insults (irradiation, DNA alkylating agents, DNA synthesis inhibitors etc.). The rationale behind these treatments is that rapidly growing cancer cells suffer more from DNA damaging insults. Unfortunately, the majority of current therapies fail to attack tumor cells specifically and hence normal cells are also being damage…

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    Protein quality control pathways in polyglutamine diseases
    2007, Rujano Maldonado,M.A. (Maria)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Zoogdiercellen bevatten duizenden verschillende eiwitten met een unieke structuur. Al deze verschillende eiwitten dienen correct gevouwen te worden in een complexe driedimensio­nale structuur om biologisch actief te zijn. Incorrect gevouwen eiwitten worden gewoonlijk snel afgebroken in de cel. Als dit niet snel genoeg gebeurt, dan kunnen niet of partieel gevouwen eiwitten e…

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    Grapes- and stonewall-related DNA damage responses in Drosophila melanogaster
    2006, Vries,H.I. de (Hilda)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Een normale celcyclus wordt op specifieke punten (checkpoints) gecontroleerd op een goed verloop van de verschillende fasen. Pas daarna deelt de cel zich en wordt DNA doorgegeven aan de dochtercellen. Als er bij een bepaald checkpoint iets niet in orde is wordt de cyclus tijdelijk gestopt en het beschadigde DNA hersteld. Checkpoint regulatie speelt dus een belangrijke r…

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    Centrosomes and cellular stress responses
    2005, Hut,H.M.J. (Henderika)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Foutjes bij het kopiëren van erfelijk materiaal, schade door zonnestraling, schade door warmte: bij celdelingen kan er veel misgaan. Promovendus Ria Hut deed onderzoek naar het centrosoom, een onderdeel in de cel dat een belangrijke rol speelt bij het in goede banen leiden van de celdeling. Bij fruitvliegjes (Drosophila melanogaster) verdwijnen bepaalde eiwitten uit het cen…

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  •  

    Disturbed protein homeostasis is a key event during cellular aging. Genetic mutations in proteins that increase the risk of protein aggregation or that impede on the protein quality control (PQC) mechanism that maintains normal protein homeostasis lead to accelerated aging or early onset of age-associated diseases.

    HSP assist in protein folding as well as protein degradation (proteasomal and autophagosomal). The central aim of my group is understand how the 100 different human HSPs are regulated to recognise their targets and steer them towards folding or degradation and how this knowledge can be exploited to combat diseases in which this protein homeostasis is disturbed.

    The main focus of my research is: what regulates the input and output of protein substrates into the so-called HSP70 machines, the central hub in the cellular PQC system?

    The subdivisions:

     

  • Student projects:

    Information will follow.

     

    You can apply via this application form.

  • CVON-dosis project Harrie Kampinga is involved with

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