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MEng PhD A.L.M.A. ten Asbroek

Position
Assistant Professor
Main activities
Education, Research
Specialisation
molecular biology, stem cell biology
Focus of research

Modelling of complex genetic retinal disorders with the use of (induced) pluripotent stem cells

Key publications
  • Smith Bradley N., Newhouse Stephen, Shatunov Aleksey, Vance Caroline, Topp Simon, Johnson Lauren, Miller Jack, Lee Younbok, Troakes Claire, Scott Kirsten M., Jones Ashley, Gray Ian, Wright Jamie, Hortobágyi Tibor, Al-Sarraj Safa, Rogelj Boris, Powell John, Lupton Michelle, Lovestone Simon, Sapp Peter C., Weber Markus, Nestor Peter J., Schelhaas Helenius J., ten Asbroek A. A., Silani Vincenzo, Gellera Cinzia, Taroni Franco, Ticozzi Nicola, van den Berg Leonard, Veldink Jan, van Damme Phillip, Robberecht Wim, Shaw Pamela J., Kirby Janine, Pall Hardev, Morrison Karen E., Morris Alex, de Belleroche Jacqueline, de Jong J. M. B. Vianney, Baas Frank, Andersen Peter M., Landers John, Brown Robert H., Weale Michael E., Al-Chalabi Ammar, Shaw Christopher E. The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder European journal of human genetics 2013;21 (1):102-108 [PubMed]
  • Aronica Eleonora, Baas Frank, Iyer Anand, ten Asbroek Anneloor L. M. A., Morello Giovanna, Cavallaro Sebastiano Molecular classification of amyotrophic lateral sclerosis by unsupervised clustering of gene expression in motor cortex Neurobiology of disease 2015;74:359-376 [PubMed]
  • Saavedra José T., Wolterman Ruud A., Baas Frank, ten Asbroek Anneloor L. M. A. Myelination competent conditionally immortalized mouse Schwann cells Journal of neuroscience methods 2008;174 (1):25-30 [PubMed]
  • ten Asbroek Anneloor L. M. A., Verhamme Camiel, van Groenigen Marjon, Wolterman Ruud, de Kok-Nazaruk Maryla M., Baas Frank Expression profiling of sciatic nerve in a Charcot-Marie-Tooth disease type 1a mouse model Journal of neuroscience research 2005;79 (6):825-835 [PubMed]
  • Fluiter Kees, ten Asbroek Anneloor L. M. A., van Groenigen Marjon, Nooij Marleen, Aalders Maurice C. G., Baas Frank Tumor genotype-specific growth inhibition in vivo by antisense oligonucleotides against a polymorphic site of the large subunit of human RNA polymerase II Cancer research 2002;62 (7):2024-2028 [PubMed]
All Publications
Research programmes

Prof. PhD F. Baas (Genome analysis / Neurogenetics)

Our mission is to identify the pathomechanisms of human genetic disease and develop new therapeutic strategies based on this knowledge.

The AMC laboratory of Genome analysis has a longstanding reputation in identification of disease genes. We use expression profiling and pathway analysis to dissect disease mechanisms. Genomics based drugs, like RNA antagonists are developed. To expedite this process, we also host the genetics core facility of the AMC.

Our research is focussed on neurodegenerative diseases, like peripheral neuropathies (Charcot-Marie-Tooth disease, CMT) and ponto-cerebellar hypoplasia (PCH), a fatal early onset neurodegenerative disease.

In this research we have identified many genes for neurogenetic diseases (CMT, ALS and PCH). Our strong link with the clinic allowed us to perform genotype-phenotype correlation. Genetic studies also showed that patients with severe neuropathies can have multiple mutations in different genes related to neuropathy. However, the contribution of additional mutations in monogenic disease causing genes is low, only a few cases show digenic inheritance. In our search for modifiers of peripheral neuropathies we identified the complement system as a major determinant for nerve regeneration. Both genetic defects of  and pharmacological intervention in activation of the complement system has a major impact of regeneration of the injured brain and nerve. Our current research is aimed at dissecting the riole of the innate immune system in neuroinflammation and its relation to disease progression. In this way we we made substantial progress in understanding the factors that influence recovery of the nervous system after trauma.

The PCH research line led to the identification of tRNA processing in brain development and degeneration. In 2008 we identified the TSEN genes as cause for PCH, this was followed by the identification of other RNA processing genes like CLP1 and EXOSC3. Our research is now directed to identify the mechanisms by which defects in (t)RNA processing lead to neurodegeneretion. To this end iPS and zebrafish models are developed.

Faculty
PhD K. Fluiter
MEng PhD A.L.M.A. ten Asbroek
MEng PhD F. van Ruissen
PhD M.A.J. Weterman

Postdocs
PhD V. Ramaglia

Others
M.E. Jakobs
S.B. Kenter
BSc R. Zwart

Prof. PhD A.A.B. Bergen (Molecular etiology of complex genetic retinal disorders)

The aim of my group is to elucidate the molecular pathology of genetic retinal disorders. In the past, we successfully identified retinal disease genes (RP12, PXE and others), brought at least one disease (PXE) from gene mapping, gene identification, mouse model, functional characterisation toward now ongoing clinical trials, and made innovative molecular models for retinitis pigmentosa, age-related macular degeneration (ZonMW pearl prize) and glaucoma. 

We currently focus on diseases of the retinal pigment epithelium (RPE; age-related macular degeneration, retinitis pigmentosa) and ganglion cells (glaucoma).We have made reliable molecular models for these diseases, and we are now applying these to develop genomics-directed personalized medicine, advanced molecular diagnostics, and/or therapies. Depending on the research question, we use(d) a variety of methodologies and technologies, including human, mouse and zebrafish genetics, genomics, bioinformatics and functional assays.

After I came to the AMC in 2014, we set up, largely externally financed, IPS-stem-cell-to-RPE-differentiation cultures (retina's in a dish) and a brand-new, non- invasive, visual screening facility for small animal models. This facility includes SLO, OCT and ERG apparatus and technology. Together, the new stem cell cultures and visual screening facility greatly enhance our possibilities to study retinal disorders in vitro and in vivo, and paves the way for the development of experimental cell and gene therapies of genetic eye disorders. Indeed, we recently injected our IPS stem cell derived RPE cells successfully subretinally in suitable animal models for age-related macular degeneration, as a first step toward high quality experimental therapy. Our new visual screening facility for small animal models has also stirred up quite some collaborative interest form researchers working on (visual aspects of) genetic metabolic diseases, AMC), neurodegenerative disease (Alzheimer I-read centre, MS, VUMC location) and the retinoblastoma expertise center (VUMC, NKI). The results of our work are further enhanced by a multitude of national and international collaborations. In the UAMC location AMC , we have collaborations with the department of GMZ, peadatrics, ophthalmology,  neurology, experimenta cardiology, medical virology,  experimental neuro-endocrinology and the organoid centre. 

Together with Prof dr CJF Boon (Ophthalmology department) we will start the first ocular genetherapy trial in the UAMC (CEP290 type retinitis pigmentosa) in 2019.
 

Postdocs
PhD R.J. Florijn
PhD Z. Sahin
MEng PhD A.L.M.A. ten Asbroek

PhD Students
V. Lo Faro
S.T. Shumet

Others
J.B. ten Brink