KTH researchers are mapping the cellular and molecular landscape of childhood diseases

The Atlas of Childhood Diseases project involves researchers from KTH, KI and SU and will run for five years, with SEK 65 million in funding from the Erling Persson foundation. It is based on a previous initiative, the Human Developmental Cell Atlas (HDCA) project, describing the early formation of the brain, spinal cord, heart and lungs in humans, mapping molecular patterns and transitions between various cell types during the first trimester.

Errors during fetal development

Now, the researchers are taking this knowledge of normal development to investigate diseases that occur in the early phases of life. The goal is to identify and map key molecules and cell types involved in the pathogenesis of diseases of the brain and spinal cord (especially cancers arising in these organs), heart (focusing on congenital structural defects), and the lungs (in relation to so-called ciliopathies affecting the airways).

“My main scientific interest lies in congenital heart disease. Our team will analyze donated fetal hearts with diagnosed structural defects. We will use state-of-the-art analysis methods to describe molecular and cellular alterations in these samples in time and space, compared to healthy development” says Enikő Lázár. In addition to the detailed characterization of these organs, their team will also try to identify genetic causes behind the observed heart defects, connecting their findings to potentially harmful genetic variants in the donors. Beyond new biological discoveries based on these insights, they also plan to provide a browsable dataset for the broad scientific community.

“In an optimal world we would succeed in all the endeavors included in this proposal. We hope that our team, by bringing together cutting-edge scientific, clinical, and technological expertise, can meaningfully broaden our understanding of the molecular underpinnings of a wide range of devastating diseases in children. An added value of our work is providing the scientific community with unique datasets, directly derived from rare - and thus very precious - pathological human tissue samples, fueling their further exploration, and serving as a basis to design therapeutic interventions later on.

Long way from bench to bedside

The researchers’ ambition is that the project’s results will eventually lead to better diagnostics and treatment options for the affected children. However, as is a common reality in basic research, it is a long way from bench to bedside. Nevertheless, their planned work on investigating pediatric tumors proposes a promising avenue, especially in combination with their effort to design therapeutic nanoparticle treatments for these diseases.

“This is the real goal. Identify the mutations and cell types that drive the tumor growth in the brain, and then act on those specific cells. For this, we need to understand the environment these cells are present in, both in terms of how they interact with neighbor cells, and how they hide from the immune system or therapeutic agents. For this work, we have a great starting point in the data collected for the Human Developmental Cell Atlas project, highlighting certain cell types that can be the origin of childhood brain tumors.”

Designing nanoparticles

In the proposal, there is a part focusing on nanoparticle development as well. The researchers will try to design nanoparticles that can act in a cell type-specific manner and carry potential drugs that would be able to affect these newly identified cell types. Enikő Lázár believes this holds the most promise for actual therapeutic intervention.

“We hope that, by developing a firm understanding of the molecular and cellular composition and spatial arrangement of certain forms of pediatric brain tumors, we will gain a firm foundation to design nanoparticles with a targeted and potent an effect to aid these diseases. It is a huge challenge, but it is important to be positive and think big.”

Text and photo: Jon Lindhe