Dr. Mike Boxem
Faculty of Science, Utrecht University
Kruytgebouw, room O508
3584 CH Utrecht
Tel. +31-(0)30-253 3714
Fax +31-(0)30-253 3655
Mike Boxem studied medical biology at the VU University Amsterdam. He performed his graduate research at the Massachusetts General Hospital in Boston, USA, and received his Ph.D. in 2002. As a postdoctoral fellow he worked in the laboratory of Dr. Marc Vidal at the Dana Farber Cancer Institute in Boston. In 2008, he started his own research group at the Department of Biology at Utrecht University, where he is now an Associate Professor in the division of Developmental Biology. He is the recipient of NWO Vidi (2010) and Vici (2017) grants, and is the coordinator of the Marie Curie ITN network ‘PolarNet’.
My group uses a combination of systems biology approaches, systematic experimental manipulation, and live-cell imaging to study the process of cell polarization. Cell polarity – the asymmetric distribution of components or functions within a cell – is a basic property of most cells that is essential in development and for the functioning of adult tissues. For example, polarity is required for the generation of different cell types through asymmetric cell divisions, and most cell types need to establish functionally distinct domains to perform their functions. Cell polarity is mediated by mutually inhibitory interactions between several groups of cortical proteins.
The most abundant polarized cell type of the animal body is the epithelial cell. Polarization of epithelial cells into apical and basolateral domains is essential for epithelia to be able to function as selectively permeable barriers. Loss of epithelial polarity contributes to epithelial diseases like polycystic kidney disease and retinal dystrophies. Moreover, epithelial cancers are characterized by loss of cell polarity and epithelial integrity, and many polarity regulators are mutated or deregulated in cancer.
Research in our group addresses three main polarity-related questions:
- What are the functional interactions that maintain polarity in existing epithelial tissues?
- What are the direct consequences of loss of polarity to the behavior and fate of cells, and how does loss of polarity predispose cells to overproliferation?
- How is cortical polarity connected with other cellular processes that contribute to cell polarity?
To address these questions, we make use of Caenorhabditis elegans as a model system. This small nematode has multiple epithelial tissues, and the proteins that control polarity are conserved between C. elegans and human. C. elegans is ideal for live observations of cell polarity due to its transparency and small number of cells. In combination with recent technological advances made possible by the use of CRISPR-based genome engineering, we can now precisely manipulate polarity in living tissues, and follow the effects on epithelial tissues and on the polarizing machinery with unprecedented detail and accuracy. Moreover, using genetic screens we can identify components that act in concert with cortical polarity regulators to establish the full polarized cell morphology.
For more information, visit the group website at http://web.science.uu.nl/developmentalbiology/boxem.html
- Amendola PG, Zaghet N, Ramalho JJ, Vilstrup Johansen J, Boxem M, Salcini AE. JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity. PLoS Genet. 2017 Feb 16;13(2).
- Portegijs V, Fielmich LE, Galli M, Schmidt R, Muñoz J, van Mourik T, Akhmanova A, Heck AJ, Boxem M, van den Heuvel S. Multisite Phosphorylation of NuMA-Related LIN-5 Controls Mitotic Spindle Positioning in C. elegans. PLoS Genet. 2016 Oct 6;12(10).
- Waaijers S, Muñoz J, Berends C, Ramalho JJ, Goerdayal SS, Low TY, Zoumaro-Djayoon AD, Hoffmann M, Koorman T, Roderick PT, Harterink M, Seelk S, Kerver J, Hoogenraad CC, Bossinger O, Tursun B, van den Heuvel S, Heck AJR, Boxem M A tissue-specific protein purification approach in Caenorhabditis elegans identifies novel interaction partners of DLG-1/Discs large. BMC Biology 2016 Aug; 14:66.
- Koorman T, Klompstra D, van der Voet M, Lemmens I, Ramalho JJ, Nieuwenhuize S, van den Heuvel S, Tavernier J, Nance J, Boxem M. A combined binary interaction and phenotypic map of C. elegans cell polarity proteins. Nat Cell Biol.. 2016 Mar;18(3):337-46.
- Waaijers S, Ramalho JJ, Koorman T, Kruse E, Boxem M. The C. elegans Crumbs family contains a CRB3 homolog and is not essential for viability. Biol. Open. 2015 Feb 6.
- de Albuquerque BF, Luteijn MJ, Cordeiro Rodrigues RJ, van Bergeijk P, Waaijers S, Kaaij LJ, Klein H, Boxem M, Ketting RF. PID-1 is a novel factor that operates
during 21U-RNA biogenesis in Caenorhabditis elegans. Genes Dev. 2014 Apr 1;28(7):683-688.
- Waaijers S, Boxem M. Engineering the Caenorhabditis elegans genome with CRISPR/Cas9. Methods. 2014 Mar 28.
- Waaijers S, Portegijs V, Kerver J, Lemmens BB, Tijsterman M, van den Heuvel S, Boxem M. CRISPR/Cas9-Targeted Mutagenesis in Caenorhabditis elegans. Genetics.
2013 Aug 26.
- *Waaijers S, *Koorman T, Kerver J, Boxem M. Identification of Human Protein Interaction Domains using an ORFeome-based Yeast Two-hybrid Fragment Library. J. Proteome Res. 2013 Jul 5;12(7):3181-92.
*These authors contributed equally
- Korzelius J, The SI, Ruijtenberg S, Prinsen M, Portegijs V, Middelkoop T, Groot Koerkamp MJ, Holstege FCP, Boxem M, and van den Heuvel S. C. elegans Cyclin D/Cdk4 and Cyclin E/Cdk2 Induce Distinct Cell Cycle Re-entry Programs in Differentiated Muscle Cells. PLoS Genetics 2011 Nov;7(11)
- van der Voet M, Berends CW, Perreault A, Nguyen-Ngoc T, Gönczy P, Vidal M, Boxem M, van den Heuvel S. NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Gα. Nat. Cell Biol. 2009 Mar;11(3):269-77.
- Boxem M, Maliga Z, Klitgord N, Li N, Lemmens I, Mana M, de Lichtervelde L, Mul JD, van de Peut D, Devos M, Simonis N, Yildirim MA, Cokol M, Kao HL, de Smet AS, Wang H, Schlaitz AL, Hao T, Milstein S, Fan C, Tipsword M, Drew K, Galli M, Rhrissorrakrai K, Drechsel D, Koller D, Roth FP, Iakoucheva LM, Dunker AK, Bonneau R, Gunsalus KC, Hill DE, Piano F, Tavernier J, van den Heuvel S, Hyman AA, Vidal M. A protein domain-based interactome network for C. elegans early embryogenesis. Cell. 2008 Aug 8;134(3):534-45.
- *Vidalain PO, *Boxem M, Ge H, Li S, Vidal M. Increasing specificity in high-throughput yeast two-hybrid experiments. Methods. 2004 Apr;32(4):363-70.
*These authors contributed equally
- *Li S, *Armstrong CM, *Bertin N, *Ge H, *Milstein S, *Boxem M, *Vidalain PO, *Han JD, *Chesneau A, Hao T, Goldberg DS, Li N, Martinez M, Rual JF, Lamesch P, Xu L, Tewari M, Wong SL, Zhang LV, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane-Kishikawa T, Li Q, Gabel HW, Elewa A, Baumgartner B, Rose DJ, Yu H, Bosak S, Sequerra R, Fraser A, Mango SE, Saxton WM, Strome S, Van Den Heuvel S, Piano F, Vandenhaute J, Sardet C, Gerstein M, Doucette-Stamm L, Gunsalus KC, Harper JW, Cusick ME, Roth FP, Hill DE, Vidal M. A map of the interactome network of the metazoan C. elegans. Science. 2004 Jan 23;303(5657):540-3.
*These authors contributed equally