Academic Center for Molecular Biomarkers in Medicine

Last updated: 365 days ago.

The aim of the ACE MolBiM is twofold:

  1. Targeted identification of potential biomarkers. Facilitated by generation of sustainable discipline-surpassing availability and search ability of (high throughput) data as well as harmonization of data sets from different resources (in vitro and in vivo laboratory models and patient samples) as well as platforms (“Compare what cannot be compared”). Effective, quality-controlled bio-informatic tools and pipelines will be applied using the existing Galaxy platform (http://bioinf-galaxian.erasmusmc.nl/galaxy/);
  2. Validation of potential biomarkers on existing and to be generated patient-based cohorts (including clinical trials related samples) using most dedicated proven quantitative and reproducible methods/ techniques. These can relate to DNA/(coding and non-coding)RNA/protein, tissue, body fluids (e.g. whole blood, urine, saliva) and derivatives thereof etc., including cell free DNA (cfDNA) and circulating tumor cells (CTCs)).
Academic Center of Excellence

Research Activities

Multiple high throughput-based activities, represented by 15 Departments, are currently ongoing to identify/validate/apply biomarkers in a clinical setting. They are heterogeneous, often on limited data/cases, due to restrains of finances and/or (patient) samples, using various analytical tools.

The ACE-MolBiM facilitates availability of informative high throughput datasets and dedicated proven informative tools. It will include analysis of targets on DNA (cell and cell-free), (coding and non-coding) RNA, and protein, generated using different platforms. The structure will be informative to allow proper decision making regarding the validity of the observations, and related conclusion about the usefulness of the potential biomarker.

Activities within the ACE will be primarily translational (discovery and validation of putative informative biomarkers) and clinical (retrospective and prospective testing of the identified biomarkers), in a collaborative effort including all relevant disciplines.

The level of excellence of the PI/groups involved in their particular field, allows an efficient translation from initial discovery, to validation and clinical implementation. This will be facilitated by the various dedicated working groups to be formed. The activities will be highly appreciated by the individual scientist/clinician, as well as the various patient support groups and funding agencies. The expertise will be recognized as fruitful partner for (inter)national collaborations.

Type of

Collaborations

The activities will be highly appreciated by the individual scientist/clinician, as well as the various patient support groups and funding agencies. The expertise will be recognized as fruitful partner for (inter)national collaborations.

Educational

Contributions

The representatives within MolBiM are active at all levels of education, including the regular curriculum Medicine: Ba, MSc, PhD, and master, as well as various postgraduate schools (Mol. Med, COEUR, NIHES, Infection & Immunity), Nanobiology and Clinical Technology.

Various PI are core teachers in these programs, and have co-organizing/(depute chair) positions in their respective committees. In addition, they are active in organizing (inter)national dedicated workshops. The quality is evaluated by standardized protocols, including visitations/audits and assessments (SETQ and D-RECT). The establishment of MolBiM will facilitate further development on dedicated educational multidisciplinary (inter)national programs, including summer schools.

In this context the following aims are defined:

  • Distribution of knowledge regarding methods/tools for investigation of high throughput datasets of different origin (laboratory models (in vitro and in vivo) as well as patient data sets);
  • Prompts for a multi-speciality way of integration in the context of biomarker discovery, validation and application in a clinical setting; - Quality controls and quality insurance will underpin education contribution;
  • all teachers/trainers will be BKO (Basis Kwaliteit Onderwijs) certified and provided with feedback via e.g. E-pass, regular internal audits and external visits;
  • Continuous recruitment of international students (4 per year).

Patient

Care Activities

No direct clinical care is part of MolBiM. However, it is highly linked based on the various activities. During (pre)-translational phase, banked patient tissues, cells, DNA/RNA/protein and fluids will be used to select potential biomarkers by the various research groups involved. Additionally, data derived from in vitro and in vivo models will be included, generated both within the Erasmus MC and outside. In the second phase, training - and validation sets will be used. Finally, potential informative biomarkers will be tested in Comparative Effectiveness Trials with emphasis on multiple randomized cohort approach, multiple data set and decision support modalities.

To achieve these goals, the ACE-MolBiM is represented by a in total 15 department, including both research as well as clinical oriented. In addition, it is strongly linked to various disease oriented ACEs, like esophago-gastric disorders, hepatopancreatobiliary -, head and neck- diseases, ocular oncology, urogenital tumors, aangeboren anatomische afwijkingen (AAA, including Expert Center Disorders of Sex Development, NFU – Rare diseases), as well as Prevention and Quantitative Methods. This will allow effective interaction between the various relevant disciplines related to the discovery, validation as well as clinical implementation of (novel) biomarkers.

Societal Relevance to Research, Education and Patient Care

MolBiM will facilitate efficient transfer of data, knowledge and techniques on putative biomarkers between disciplines related to various diseases. It will stimulate usage of (publically) available, often sub-optimally used, but quality checked, high throughput datasets. Moreover, it will implement relevant novel detection and analytical methods and tools. The platform under construction, based on dedicated working groups, will stimulate understanding health and diseases, including both disease-specific and covering parameters.

The expertise present will allow testing relevant populations/cohorts/ samples, amplifying the power and limiting the waste (including costs). If a biomarker is classified as potentially interesting during the discovery and validation phase, it will be further developed in the context of possible valorization (collaboration with TTO), with the aim to develop a clinical applicable, easy to use, validated test.

These can be related to prevention, diagnosis, prognosis and prediction (personalized medicine), including the best statistical methods, both related to single center- or multicenter studies. Therefore, close collaboration is established with relevant ACEs including Quantitative Methods. Collaboration with industrial partners will be activated, and related guidelines will be developed. The knowledge and knowhow will be used to further developed an informative and state of the art educational program at different levels.

Viability of Research, Education and Patient Care

MolBiM is a collaboration between 15 departments, each specialized in defined fields of human health and disease. It includes various disciplines (oncological as well as non-oncological), related to patients at different ages. The platform will facilitate a continuous available (and growing) dataset of harmonized high throughput findings, to be shared for identification and validation of biomarkers, resulting in final implementation.

It is combined with informative and optimally suited tools and techniques, for detection of the potential biomarker in biological samples of different origin. Criteria for handling and storage of tissue/cells/fluids and (clinical) data will be defined (OECD, NCI, ISBER). METC approval, of research and privacy will be uniformly defined and applied, including biobank rules on governance. The various methods/approaches will be made available as SOPs, facilitating a wealth of standardized tools to be applied. It will uniquely facilitate a platform allowing scientists/clinicians, and especially talented PhD students, to efficiently obtain the required information for their particular research.

The PIs are recognized as specialized within their specific field of interest, proven by their (inter)national status and related in- and output, demonstrated by their activity in various guideline and meeting-organizing committees. A significant number of successful PhD graduates continue their career internationally.

Key and relevant publications of the last five years

  • Junker K, Heinzelmann J, Beckham C, Ochiya T, Jenster G. Extracellular Vesicles and Their Role in Urologic Malignancies. Eur Urol. 2016 Feb 25. pii: S0302-2838(16)00224-4. (IF 13.938; in progress)
  • Erdem-Eraslan L, van den Bent MJ, Hoogstrate Y, Naz-Khan H, Stubbs A, van der Spek P, Böttcher R, Gao Y, de Wit M, Taal W, Oosterkamp HM, Walenkamp A, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, van der Holt B, Vernhout RM, Sillevis Smitt PA, Kros JM, French PJ. Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial. Cancer Res. 2016 Feb 1;76(3):525-34. (IF 9.329; in progress)
  • Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus. Kastelein F, Biermann K, Steyerberg EW, Verheij J, Kalisvaart M, Looijenga LH, Stoop HA, Walter L, Kuipers EJ, Spaander MC, Bruno MJ; ProBar-study group. Gut. 2013 Dec;62(12):1676-83. (IF 10.111; cited 74)
  • Fritz H Schröder, Jonas Hugosson, Monique J Roobol, Teuvo LJ Tammela, Marco Zappa, Vera Nelen, Maciej Kwiatkowski, Marcos Lujan, Liisa Määttänen, Hans Lilja, Louis J Denis, Franz Recker, Alvaro Paez, Chris H Bangma, Sigrid Carlsson, Donella Puliti, Arnauld Villers, Xavier Rebillard, Matti Hakama, Ulf-Hakan Stenman, Paula Kujala, Kimmo Taari, Gunnar Aus, Andreas Huber, Theo H van der Kwast, Ron HN van Schaik, Harry J de Koning, Sue M Moss, Anssi Auvinen, ERSPC Investigators. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 384 (9959): 2027-2035, 2014. (IF 38.278; cited 290)
  • Gröschel S, Sanders MA, Hoogenboezem R, de Wit E, Bouwman BA, Erpelinck C, van der Velden VH, Havermans M, Avellino R, van Lom K, Rombouts EJ, van Duin M, Döhner K, Beverloo HB, Bradner JE, Döhner H, Löwenberg B, Valk PJ, Bindels EM, de Laat W, Delwel R. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 2014; 157(2):369-81. (IF 22.268; cited 86)
  • Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, De la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Döhner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab (GA101) plus chlorambucil in patients with CLL and comorbidity. New Engl J Med 2014;370:1101-1110. (IF 55.873; cited 419)
  • Liu NQ, Stingl C, Look MP, Smid M, Braakman RB, De Marchi T, Sieuwerts AM, Span PN, Sweep FC, Linderholm BK, Mangia A, Paradiso A, Dirix LY, Van Laere SJ, Luider TM, Martens JW, Foekens JA, Umar A. Comparative proteome analysis revealing an 11-protein signature for aggressive triple-negative breast cancer. J Natl Cancer Inst. 2014 106: djt37. (IF 12.583; cited 27)
  • Impact of surveillance for Barrett's oesophagus on tumour stage and survival of patients with neoplastic progression. Kastelein F, van Olphen SH, Steyerberg EW, Spaander MC, Bruno MJ; ProBar-study group. Gut. 2016 Apr;65(4):548-54. (IF [2016] 14.66; cited 4)
  • Rockova V, Abbas S, Wouters BJ, Erpelinck CAJ, Beverloo HB, Delwel R, van Putten WLJ, Löwenberg B, Valk PJM. Risk-stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers. Blood. 2011; 118(4):1069-76. (IF 9.898; cited 68)
  • Cunningham JJ, Ulbright TM, Pera MP, Looijenga LHJ. Lessons from human teratomas to guide development of safe stem cell therapies. Nature Biotechn. 2012: 340(9):849-857. Cunningham JJ, Ulbright TM, Pera MF, Looijenga LHJ. Lessons from human teratomas to guide development of safe stem cell therapies. Nat Biotechnol. 2012; 30: 849-857. (IF 32.438; cited 79)

PhD theses of the last five years

  • I. Teles Alves: Characterization of Novel Genetic Alterations in Prostate Cancer, 2015 (Promotoren Prof.dr.ir. J. Trapman, Prof.dr.ir. G. Jenster)
  • L. Erdem-Eraslan: Identification of Predictive Response Markers and Novel Treatment Targets for Gliomas, 2016 (Promotor Prof. dr. P.A.E. Sillevis Smit)
  • E. den Boer: Therapeutic Drug-Monitoring of Methotrexate-Polyglutamates in Rheumatoid Arthritis, 2014 (Promotor Prof. dr. J. Lindemans)
  • C.M.M. Gits : MicroRNAs in the tumor biology of soft tissue sarcomas. 2013 (Promotor Prof. dr. S. Sleijfer &, J. Verweij)
  • M.A. Rijlaarsdam: Functional genomics of germ cell tumors; from balls to bytes and back again, 2014 (Promotor Prof. dr. L.H.J. Looijenga)
  • J. Kaprova: Malignant germ cell tumors and disorders of sex development: towards clinical implementation, 2015 (Prof. dr. L.H.J. Looijenga)
  • C.H.M. Leenen: Diagnostic Strategies for Early Lynch Syndrome Detection, from molecular testing to economic evaluation, 2015 (Promotors: Prof. dr. E.J. Kuipers, Prof. dr. E.W. Steyerberg)
  • M. Sanders: Computational Biology-Driven Genomic and Epigenomic Delineation of Acute Myeloid Leukemia, 2015 (Promotoren Prof. dr. H.R. Delwel, Prof. dr. B. Löwenberg)
  • F.H. Jansen: Discovery and validation of prostate cancer biomarkers, 2013 (Promotor Prof.dr.ir. G. Jenster)
  • V. Rockova: Bayesian Variable Selection in High-dimensional Applications, 2013 (Promotoren Prof.dr. E.M.E.H. Lesaffre, Prof. dr. B. Löwenberg)

Non-scientific publications related to the ACE

Principal coordinator(s)