Research

Tightly linked to the Boston Medical Center (BMC), we ask ourselves fundamental questions such as: How can we improve the quality of patients’ lives. What drives and controls cellular plasticity in development and tumor resistance? How do cells transcriptionally respond to targeted therapies and how can we steer it in the right direction? What is the role of signaling and cell communcation within the (tumor) microenvironment? And how can we ultimately leverage our knowledge to identify better biomarkers or novel therapy strategies?

To answer these questions we make use of state-of-the-art facilities and technologies and aim to mimick such biological processes using 3D multi-cellular in vitro models, such as (tumor) organoids and spheroids. These systems can then be challenged through genetic engineering and be profiled using a wide-array of genomics and imaging technologies.

We focus on biological processes that control the decision making of an individual (cancer) cell. These processes range from extracelluar cues, such as signaling pathways and cell-to-cell interactions, to intracellular mechanisms that control the cell’s fate and its ability to (de-)differentiate, such as chromatin reorganization and transcriptional processing.

 

Projects

Here we present a number of ongoing research interests in the lab. However we also strive to stimulate each individual’s creativity and are thus happy to brainstorm about other potential projects that fit within our research expertise and interest. In addition, we encourage potential postdocs to apply for independent funding to grow both as an individual and researcher.

 

Mechanistic insights in the role of microenvironmental cell-to-cell interactions

The potential of a cell, such as a progenitor cell or tumor cell, is not only determined by its intracellular regulatory network, but also by the instructions it receives from the extracellular environment. One rapid way of cell-to-cell communication is through direct contact and here we will assess the role of the microenvironmental cell-type composition in a manner that preserves the spatial information using techniques such as spatial omics.

 

Role of protein mediated looping at the nucleosome scale

Chromatin reorganization has been studied extensively at large scale (A/B compartments, TADS, …), however relatively little is known about chromatin organization at the gene regulatory level. In this project we will combine targeted perturbations with high-resolution looping data to unravel the role of transcription factors and other DNA binding elements. This information will be subsequently leveraged to identify novel vulnerabilities in selected cancer types, such as the potential to drug the non-coding looping regions of the genome.

 

Coupling transcription and cell-cycle

Recent evidence suggests that RNA transcription and DNA replication are not completely independent processes. In this project we will generate data to create an integrative model and use this to design novel data-driven therapeutic strategies to target transcriptionally active and fast cycling tumor cells.