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Professor M.H.M. (Marca) Wauben, PhD

Tuesday 2 October 2012

Department of Biochemistry & Cell Biology, Faculty of Veterinary Medicine, Utrecht University
Prof.dr. Marca Wauben, PhD & Esther Nolte-’t Hoen, PhD

Intercellular communication via cell-derived vesicles is nowadays recognized as an important route for the development and maintenance of multi-cellular organisms. This field of research has recently attracted much attention and a large number of publications indicate that cells can use these vesicles for modulating the function of other cells. Most cell types, if not all, can release vesicles, and these vesicles are present in all body fluids. An important aspect of vesicle-mediated communication is that cells can actively regulate the release and composition of such vesicles. This allows cells to incorporate specific ‘address code’ proteins and signaling molecules in the vesicles. As a result, these vesicles can bind and modulate the function of selected recipient cells.

Our research group aims to unravel how vesicles derived from immune cells contribute to regulation of immune responses. We have studied how immunologically important proteins such as MHC class II end up in vesicles released by dendritic cells (DC) and showed that the antigen-specific interaction between DC and CD4+ T cells stimulates the release of vesicles from both cell types. We also identified ‘address code’ proteins for vesicles produced by DC. Our current research focuses on characterizing the heterogeneity of vesicle populations released by immune cells and which functions the different vesicle types have. Due to their small size, detailed characterization of vesicles is technically difficult. Our group has a leading position in the development and application of various techniques to isolate and characterize different vesicle types. We recently developed a high resolution flow cytometry-based method to investigate the number and composition of nano-sized vesicles in detail. We also study which types of cell-derived vesicles are present in various body fluids and how these could interfere in immune-related processes. Vesicles found in breast milk, for example, contain many immune-modulatory proteins and we investigate whether cell-derived vesicles in milk can instruct the infant’s immune system. The genetic information carried by cell-derived vesicles consists mostly in small non-coding RNA molecules, which are now thought to be important regulators of gene expression. These genetic messages transferred via vesicles can have great impact on the function of vesicle-targeted cells. We have recently published a comprehensive deep sequencing analysis of small RNA species in immune cell-derived vesicles. Exciting RNA biotypes have been detected, which could be involved in gene regulation. The function of these RNAs during intercellular communication will be investigated in the near future.

Research programme:
1) Basic research: The role of dendritic cell and T cell-derived vesicles in tuning adaptive immune responses. We aim to reveal factors that influence the selection of vesicular cargo (proteins and (small)RNAs) and the release of different vesicle subsets. Furthermore, emphasis is on the identification and modulation of cells specifically targeted by these vesicles.
2) (Pre)clinical research: i) Identification of vesicle-based biomarkers. Emphasis is on the characterization of vesicles in breast milk. ii) Cell-derived vesicle inspired carriers for clinical application
3) Technical research: Development/Optimization of methods for the isolation and characterization of (nano-sized)vesicles


Current research group:
Marca Wauben (Professor 'Intercellular Communication')
Esther Nolte-‘t Hoen (Senior Scientist)
Toine ten Broeke (Postdoc)
Els van der Vlist (PhD student)
Marijke Zonneveld (PhD student)
Mieke de Boer-Brouwer (Technician)

Marca Wauben is Member of the ISEV (International Society of Extracellular Vesicles) Executive Board (www.isev.org)

Publications 2012:

Nolte-’t Hoen EN, Buermans HP, Waasdorp M, Stoorvogel W, Wauben MH, ’t Hoen PA. Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res. 2012 Jul 19. [Epub ahead of print]

Aalberts M, Sostaric E, Wubbolts R, Wauben MW, Nolte-’t Hoen EN, Gadella BM, Stout TA, Stoorvogel W. Spermatozoa recruit prostasomes in response to capacitation induction. Biochim Biophys Acta. 2012 Aug 24. [Epub ahead of print]

van der Vlist EJ, Nolte-’t Hoen EN, Stoorvogel W, Arkesteijn GJ, Wauben MH. Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry. Nature Protocols 2012;7(7):1311..

Hoen EN, van der Vlist EJ, Aalberts M, Mertens HC, Bosch BJ, Bartelink W, Mastrobattista E, van Gaal EV, Stoorvogel W, Arkesteijn GJ, Wauben MH. Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles. Nanomedicine 2012; 8(5):712.

Nolte-’t Hoen EN, Wauben MH. Immune cell-derived vesicles: Modulators and mediators of inflammation. Curr Pharm Des. 2012; 18(16):2357. Review

Aalberts M, van Dissel-Emiliani FM, van Adrichem NP, van Wijnen M, Wauben MH, Stout TA, Stoorvogel W. Identification of Distinct Populations of Prostasomes That Differentially Express Prostate Stem Cell Antigen, Annexin A1, and GLIPR2 in Humans. Biol Reprod. 2012; 86(3):82.


14/09/2012 | Faculty of Veterinary Medicine Life Sciences Inaugural lecture Prof M.H.M. Wauben, PhD
Cells ‘communicate’ with each other via membrane vesicles

Communicerende cellen, Ig Nobelprijzen en exoplaneten Labyrint Radio | Zondag 23 sepCellen scheiden kleine membraanblaasjes uit. Afval, werd er lange tijd gedacht. Nu blijken ze toch een functie te hebben.