Child research

STRATEGIC THEMES: INTERDISCIPLINARITY
Empowering the entire family
Center of Excellence for Rehabilitation Medicine
(De Hoogstraat Rehabilitation)
Advances in medical technology, diagnosis and treatment have increased the life expectancy
of various childhood disorders. Pediatric rehabilitation aims to optimize autonomy, selfmanagement
and participation of children with developmental disabilities and their families.
Our interdisciplinary program focuses on developmental trajectories, identification of children
at risk for physical and mental health problems and interventions to mitigate those risks.
Because families are central in the lives and development of children, we also focus on family
empowerment.
Patients and families are involved throughout our research process, from idea to
implementation, and we have a strong collaboration with patient organizations, including
Cerebral Palsy Netherlands (CP Nederland; formerly known as BOSK). A good example is our
study on sleep, nutrition and physical activity of children with Brain Based Developmental
Disabilities. Together with Neonatology, we’ve developed clinical care pathways to guide
clinicians with assessment and early identification of problems in these areas, based on
systematic data collection. We seek to understand the quantity and quality of sleep and its
relationship with development. In partnership with parents, we’re developing a support
program, including an instructional video and online knowledge translation resources, to
educate and empower families so they can support the development and health of their child.
mketela2@umcutrecht.nl
We collaborate with
patients and families in all
stages of research.
- Marjolijn Ketelaar
Marjolijn Ketelaar,
PhD focuses on the
development of children
with developmental
disabilities, and
empowerment of
families to optimize
autonomy and
participation.
Novel insights into cancer immunotherapy
mboes@umcutrecht.nl
Marianne Boes,
PhD focuses on
immunodeficiencies
and immune activation
with a special
interest in immune
checkpoints and
developing immunotherapy
for cancer
patients.
Immunotherapy based on checkpoint blocking antibodies (anti CTLA4, anti PD-1) has
revolutionized treatment for patients suffering from well-responding cancers such as
melanoma and non-small cell lung cancer, which are tumors with acquired mutational loads.
Neuroblastoma accounts for 15% of childhood cancer mortality, yet susceptibility to
checkpoint blockade-based immunotherapy is not evident. Because the level of expression
of major histocompatibility (MHC) Class-I molecules is low, neuroblastoma tumors evade a
major immune defense strategy based on MHC-restricted cytotoxic T cells. In our opinion,
induction of MHC-I membrane expression is prerequisite for optimal efficacy of T-cell therapy
in neuroblastoma and should be incorporated into treatment regimens.
My team initiated an interdisciplinary collaboration with colleagues at the Netherlands
Cancer institute to screen for targets that upregulate MHC-I display at the neuroblastoma cell
surface, yielding TNIP1 and N4BP1. Validation experiments in neuroblastoma revealed
increased MHC-I antigen presentation capacity and induced recognition by neuroblastoma
tumor-antigen specific T-cells. Supporting our findings, patients expressing high levels of
TNIP1 and N4BP1 in neuroblastoma have lowered MHC-I tumor surface display and have
worse survival probability. Use of these targets in therapy has the potential to augment
current treatments in innovative ways that will improve clinical outcomes for neuroblastoma
cancer patients.
UMC Utrecht - Child research 37