Department of Metabolic Diseases
University Medical Center Utrecht
Room KE.03.139.2
Lundlaan 6
3484 EA Utrecht
The Netherlands
phone: 088 - 755 49 21
email:
a.b.brenkman@umcutrecht.nl
Dietary Restriction (DR), the reduction of food intake without malnutrition, is the only robust metabolic intervention that increases lifespan in all organisms tested. Strikingly, it also delays the onset of numerous age-related diseases such as diabetes mellitus, neurodegeneration and cancer.
The response to DR is highly regulated and evolutionary conserved but the underlying molecular mechanisms remain largely elusive. Interestingly, a key role for the Forkhead transcription factor FoxA in the DR response has recently been described.
Our laboratory has a long-time interest in the biology of Forkhead transcription factors for which we merge state-of-the-art metabolomics and proteomics Mass Spectrometry based technologies (Orbitrap MS, GC-TOF, Triple-Quad and Q-TOF) with classic Molecular Biology techniques including Q-PCR, siRNA, Microarray Expression Profiling, Multiplex ELISA and intracellular protein replacement.
Arjan B. Brenkman graduated from Biomedical Sciences at the University of Utrecht in
1998 (Cum laude) during which he performed a one-year internship at Novartis Pharma in Basel.
He then joined the lab of Prof. Dr. P.C. van der Vliet at the department of Physiological Chemistry of the Utrecht University, working on an in vitro Adenovirus DNA replication system, which led to a thesis on the molecular architecture and function of Adenovirus DNA polymerase in 2002. He collaborated extensively with the groups of Prof. Dr. Margarita Salas and Prof. Dr. Luis Blanco, Universidad Autonoma, Madrid, Spain, where he worked for three months as part of this collaboration.
Subsequently he joined the groups of Prof. Dr. Ir. B.M.T. Burgering and Prof. Dr. J.L. Bos, from the Cancer Genomics Centre at the UMC Utrecht as a post-doc in spring 2003 to identify novel protein interaction partners of signal transduction molecules in mammalian cells. Understanding the regulation of the transcription factor FOXO4, which functions at the crossroads of tumour suppression and longevity regulation particularly captured his interest. For this, he was trained in Mass Spectrometry technology in the lab of Prof. Dr. Albert Heck, director of the Netherlands Proteomics Centre and head of the Department of Biomolecular Mass Spectrometry, Utrecht University and used this training to set up and head a Mass Spectrometry lab (Nano-electrospray Quadrupole Time-of-Flight MS) to explore proteins for identification, post-translational modification and quantitative proteomics.
As of January 2008 he has joined the Department of Metabolic and Endocrine diseases, headed by Dr. L. Klomp/ Prof. Dr. Ruud Berger as an Assistant Professor, to pursue his own research interest, which will integrate Metabolomics research into biology. Together with Dr. Margriet Hendriks and Prof. Dr. Ruud Berger he coordinates and develops the Netherlands Metabolomics Centre Utrecht.
Dr. Rogier van Gent, postdoc
Dr. Edwin Stigter, postdoc
Dr. Sofia Letsiou, postdoc
Dr. ir. Gerdine Stout, postdoc
Stiaan Labuschagne, PhD student
Ing. Niels van den Broek, technician 
Ing. Johan Gerrits, technician
Ing. Aukje Veenstra, technician
The DNA damage repair protein Ku70 interacts with FOXO4 to coordinate a conserved cellular stress response. Brenkman AB, van den Broek NJ, de Keizer PL, van Gent DC, Burgering BM. FASEB J. 2010 Jun 22. [Epub ahead of print]
- Van Loosdregt J, Vercoulen Y, Guichelaar T, van Gent YYJ, van Beekem O, Beekman Y, Hijnen D.J., Mutis T, Brenkman AB, Kalkhoven E, Prakken BJ, and P. Coffer. Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. Blood. 2009 Dec 7.
- Tobias B. Dansen, Alida Smit, Miranda van Triest, van Leenen D, M. Groot-Koerkamp, A.A. Szypowska, P.L.J. de Keizer, Meppelink, A, Arjan B. Brenkman, Yodoi, S.K.Y, Frank C. Holstege and Boudewijn M.T. Burgering. Redox-sensitive cysteines bridge p300-mediated acetylation and FoxO4 activity. Nat Chem Biol. 2009 Sep;5(9):664-72. Epub 2009 Aug 2.
- Brenkman AB, de Keizer PLJ, van den Broek NJF, van der Groep P, van Diest PJ, van der Horst A, Smits AMM, Burgering BMT. The peptidyl-isomerase Pin1 regulates p27Kip1 expression through inhibition of FOXO tumorsuppressors. Cancer Res. 2008 Sep15;68(18): 7597-605.
- Brenkman AB, de Keizer PLJ, van den Broek NJF, Jochemsen AG, Burgering BMT. Mdm2 induces mono-ubiquitination of FOXO4. PLoS ONE. 2008 Jul 30;3(7):e2819.
- Jelluma N, Brenkman AB, McLeod I, Yates JR 3rd, Cleveland DW, Medema RH, Kops GJ. Chromosomal instability by inefficient Mps1 auto-activation due to a weakened mitotic checkpoint and lagging chromosomes. PLoS ONE. 2008 Jun 11;3(6).
- Jelluma N, Brenkman AB, van den Broek NJ, Cruijsen CW, van Osch MH, Lens SM, Medema RH, Kops GJ. Mps1 Phosphorylates Borealin to Control Aurora B Activity and Chromosome Alignment. Cell. 2008 Jan 25;132(2):233-246.
- Brenkman AB, Burgering BM. Live Longer through PHAsting. Cell Metab. 2007 Jun;5(6):407-9.
- van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM, Burgering BM. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 2006 Oct;8(10):1064-73.
- Lebbink RJ, de Ruiter T, Adelmeijer J, Brenkman AB, van Helvoort JM, Koch M, Farndale RW, Lisman T, Sonnenberg A, Lenting PJ, Meyaard L. Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1. J Exp Med. 2006 Jun 12;203(6):1419-25.
- Brenkman AB, Burgering BM. FoxO3a eggs on fertility and aging. Trends Mol Med. 2003 Nov;9(11):464-7.
- 2009: University of Utrecht, Immunity and Infection Focus area grant for a 3-yrs post-doctoral researcher
- 2009: UMC Utrecht grant for a 3-yrs technician
- 2008: NMC instrumentation grant for the acquisition of a LTQ-Orbitrap XL Mass Spectrometer plus nano-LC setup.
- 2008: NMC core project grant for a 3-yrs post-doctoral researcher.
- 1998: Organon Young Talent Research Award, acknowledged by the Royal Dutch Academy of Sciences (KNAW).
Latest update: July 19, 2010