Kerensa Broersen

Complex Protein Biochemistry

Kerensa Broersen, Nanobiophysics Group, University of Twente

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Research in the Broersen lab

Complex Protein Biochemistry

Protein misfolding can lead to protein self-assembly into larger aggregated structures. Hence, this process plays a role in a large and extending variety of diseases, including Alzheimer’s and Parkinson’s disease, type 2 diabetes mellitus, various types of cancer, ALS and prion diseases. The upside of this process is that protein aggregates can also play a functional role, both in vivo in the animal kingdom as well as as structuring agent in the formation of food texture upon processing as protein misfolding can be induced by means of processing conditions.

Even though diseases such as Alzheimer’s disease and ALS have been solidly related to the formation of small aggregates early in disease progress, no cure is available for many of these diseases. Similarly, protein aggregates are little employed at the moment as functional added materials in the food industry because, even though research efforts are extensive, the impact of the complexity of the food matrix is little understood. Understanding the complexity and impact of co-occurring factors, whether in the brain or in food, can crucially impact on the protein aggregation process. We aim to investigate the influence that such complexity may have. We use chiptechnology, single molecule detection techniques, microfluidic systems and advanced biophysical and biochemical assays as well as cell cultures to support our studies.








Former lab members

Ellen Hubin

Annelies Vandersteen

Wim Jonckheere

Ageeth Soldaat

Adriani Kourkouli

Josey Sueters

Lisette Bosman

Stanislav Rudyak

Iris Verhoek

Elske Cornelisse

Lisanne Dijk

Rick Brockötter







Publication list

Hubin E, Vanschoenwinkel B, Broersen K, De Deyn PP, Koedam N, van Nuland NA, Pauwels K. (2016). Could ecosystem management provide a new framework for Alzheimer’s disease? Alzheimers Dement. 12: 65-74.e1.

Hubin E, Deroo S, Schierle GK, Kaminski C, Serpell L, Subramaniam V, van Nuland N, Broersen K, Raussens V, Sarroukh R (2015). Two distinct β-sheet structures in Italian-mutant amyloid-beta fibrils: a potential link to different clinical phenotypes. Cell Mol Life Sci. 72: 4899-4913.

Barrera Guisasola EE, Andujar SA, Hubin E, Broersen K, Kraan YM, Mendez L, Delpiccolo CML, Masman MF, Rodiguez AM, Enriz RD (2015). New mimetic peptide inhibitors of Aβ aggregation. Molecular guidance for rational drug design. Eur J Med Chem. 95: 136-152.

Hubin E, van Nuland NAJ, Broersen K, Pauwels K (2014). Transient dynamics of Abeta contribute to toxicity in Alzheimer’s disease. Cell. Mol. Life Sci. 71: 3507-3521.

Broersen K (2014). Technical proteins: a multitude of applications to discover. Editorial for Journal of Physical Chemistry & Biophysics. 4: e124, doi: 10.4172/2161-0398.1000e123.

Adrover M, Marino L, Sanchis P, Pauwels K, Kraan Y, Lebrun P, Vilanova B, Munoz F, Broersen K, Donosa J (2014). Mechanistic insights in glycation-induced protein aggregation. Biomacromolecules 15: 3449-3462.

Munialo CD, de Jongh HHJ, Broersen K, van der Linden E, Martin AH (2013). Modulation of the gelation efficiency of fibrillar and spherical aggregates by means of thiolation. J. Agric. Food Chem. 61: 11628-11635.

Chávez-Gutiérrez L, Bammens L, Benilova I, Vandersteen A, Benurwar M, Borgers M, Lismont S, Zhou L, Van Cleynenbreugel S, Esselmann H, Wiltfang J, Serneels L, Karran E, Gijsen H, Schymkowitz J, Rousseau F, Broersen K, De Strooper B (2012). The mechanism of γ-secretase dysfunction in familial Alzheimer disease. EMBO J. 31: 2261-2274.

Pauwels K, Williams TL, Morris KL, Jonckheere W, Vandersteen A, Kelly G, Schymkowitz J, Rousseau F, Pastore A, Serpell LC, Broersen K. (2012). Structural basis for increased toxicity of pathological Aβ42 : Aβ40 ratios in Alzheimer’s disease. J. Biol. Chem. 287: 5650-5660.

Siekierska A, De Baets G, Reumers J, Gallardo R, Rudyak S, Broersen K, Couceiro J, Van Durme J, Schymkowitz J, Rousseau F (2012). α-Galactosidase aggregation is a determinant of pharmacological chaperone efficacy on Fabry disease mutants. J. Biol. Chem. 287: 28386-28397.

Vandersteen A, Masman MF, De Baets G, Jonckheere W, van der Werf K, Marrink SJ, Rozenski J, Benilova I, De Strooper B, Subramaniam V, Schymkowitz J, Rousseau F, Broersen K (2012). Molecular plasticity regulates oligomerization and cytotoxicity of multi-peptide length Aβ pool. J. Biol. Chem. 287: 36732-36743.

Vandersteen A, Hubin E, Sarroukh R, De Baets G, Schymkowitz J, Rousseau F, Subramaniam V, Raussens V, Wenschuh H, Wildemann D, Broersen K (2012). A comparative analysis of the aggregation behaviour of amyloid-β peptide variants. FEBS Lett. 586: 4088-4093.

Zhou L, Brouwers N, Benilova I, Vandersteen A, Mercken M, Van Laere K, Van Damme P, Demedts D, Van Leuven F, Sleegers K, Broersen K, Van Broeckhoven C, Vandenberghe R, De Strooper B (2011). Amyloid Precursor Protein mutation E682K at the alternative β-secretase cleavage β’-site increases Aβ generation. EMBO Mol. Med. 3: 291-302.

Broersen K, Jonckheere W, Rozenski J, Vandersteen A, Rousseau F, Schymkowitz J (2011). A standardized dissolution procedure for hydrophobic amyloid beta peptide. Protein Eng. Design Sel. 24: 743-750.

Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M, Vandersteen A, Bartic C, d’Hooge R, Martins IC, Rousseau F, Schymkowitz J, De Strooper B (2010). The neurotoxicity of Alzheimer’s disease related amyloid beta peptides is caused by intermediate conformations stabilized by small changes in the Aβ42 to Aβ40 ratio. EMBO J. 29: 3408-3420.

Broersen K, Rousseau F, Schymkowitz J (2010). The culprit behind amyloid beta peptide related neurotoxicity in Alzheimer’s disease: oligomer size or conformation? Alzheimers Res. Ther. 2: 12.

Weijers M, Broersen K, Barneveld PA, Cohen Stuart MA, Hamer RJ, De Jongh HH, Visschers RW, (2008). Net charge affects morphology and visual properties of ovalbumin aggregates. Biomacromolecules 9: 3165-3172.

Connell E, Darios F, Broersen K, Gatsby N, Peak-Chew SY, Rickman C, Davletov B (2007). Mechanism of arachidonic acid action on syntaxin/munc18. EMBO Reports 8: 414-419.

Broersen K, Weijers M, de Groot J, Hamer RJ, de Jongh HHJ (2007). Effect of protein charge on the generation of aggregation-prone conformers. Biomacromolecules. 8: 1648-1656.

Broersen K, Elshof M, De Groot J, Voragen AGJ, Hamer RJ, De Jongh HHJ (2007). Aggregation of β-lactoglobulin regulated by glucosylation. J. Agric. Food Chem. 55: 2431-2437.

Broersen K, van Teeffelen AM, Vries A, Voragen AG, Hamer RJ, de Jongh HH (2006). Do sulfhydryl groups affect aggregation and gelation properties of ovalbumin? J. Agric. Food Chem. 54: 5166-5174.

Broersen K, van den Brink D, Fraser G, Goedert M, Davletov B (2006). Alpha-synuclein adopts an alpha-helical conformation in the presence of polyunsaturated fatty acids to hinder micelle formation. Biochemistry 45: 15610-15616.

Van Teeffelen AM, Broersen K, de Jongh HH (2005). Glucosylation of beta-lactoglobulin lowers the heat capacity change of unfolding: a unique way to affect protein thermodynamics. Protein Science 14: 2187-2194.

Broersen K, Voragen AG, Hamer RJ, de Jongh HH (2004). Glycoforms of beta-lactoglobulin with improved thermostability and preserved structural packing. Biotechnol. Bioeng. 86: 78-87.

Kosters HA, Broersen K, de Groot J, Simons JW, Wierenga P, de Jongh HH (2003). Chemical processing as a tool to generate ovalbumin variants with changed stability. Biotechnol. Bioeng. 84: 61-70.

Broersen K, de Jongh HHJ (2003). Potential of beta-lactoglobulin glycosylation for industrial applications. Industrial Proteins 11: 6-8.

Book chapter

De Jongh HHJ, Broersen K (2012). Application potential of food protein modification. Book chapter in “Advances in Chemical Engineering”, Nawaz Z (Ed.). ISBN: 978-953-51-0392-9. InTech, DOI: 10.5772/32114.


De Jongh HHJ, Broersen K (23.12.05) Controlled gelation of protein mixture. Patent no. 05112947.6- European Patent Office.

Conference Proceedings

Sarroukh R, Hubin E, Serpell LC, van Nuland NAJ, Broersen K, Raussens V (2014). Alzheimer’s disease and cerebral amyloid angiopathy, doppelgangers? 28th Annual Symposium of the Protein Society, San Diego USA, Protein Science 23: 86.

Hubin E, Van Nuland N, Broersen K (2011). Effect of apoE isoform and lipidation status on proteolytic clearance of the amyloid-beta peptide. 8th EBSA European Biophysics Congress, Budapest, Hungary in: European Biophysics Journal with Biophysics Letters 40 (1): 89-90.

Vandersteen A, Benilova I, Jonckheere W, Rousseau F, Schymkowitz J, Broersen K (2011). Biophysical consideration of gamma-secretase modulation as potential target for Alzheimer’s disease. 8th EBSA European Biophysics Congress, Budapest, Hungary in: European Biophysics Journal with Biophysics Letters 40 (1): 95.

Benilova I, Chong SA, Kuperstein I, Broersen K, Schymkowitz J, Rousseau F, Bartic C, Callewaert G, De Strooper B (2010). The A-beta 42/40 ratio is a driver of acute synaptotoxicity and LTP impairment. 7th Int. Meeting on Substrate-Integrated Microelectrodes.

Benilova I, Kuperstein I, Broersen K, Schymkowitz J, Rousseau F, Bartic C, De Strooper B (2009) MEA neurosensor, the tool for synaptic activity detection: acute amyloid-β oligomers synaptotoxicity study. IFMBE Proceedings 25/VIII, ed. by O. Dössel and W. Schlegel (Springer), 314-316.

Broersen K, Davletov B (2007). Lipids and α-synuclein aggregation in Parkinson’s disease. 21st Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinson’s Disease and Other Movement Disorders, Washington DC, USA in: Movement Disorders 22: VI-VI.