We have a specific interest in dissecting the clonal heterogeneity of leukemias and recently developed tools that allow us to identify and prospectively isolate genetically distinct clones within individual patients. A similar level of heterogeneity is seen within the tumor microenvironment in the bone marrow of patients, and we aim to functionally characterize stromal cells and various innate and adaptive immune cells in the context of developing leukemic clones.
We perform gene-function analyses in human hematopoietic stem and progenitor cells isolated from cord blood and bone marrow utilizing various strategies including optimized CRISPR/Cas9 approaches. We have a longstanding expertise in using molecular approaches (transcriptome, proteome, metabolome and epigenome) to further understand processes such as hematopoietic differentiation, proliferation, apoptosis and self-renewal.
We make use of humanized niche xenograft models in which 3D scaffolds coated with human stromal cells are implanted in mice in order to mimic that situation in leukemia patients as closely as possible. Furthermore, we directly collaborate with the clinical and diagnostic departments at the UMCG and have banked large longitudinal series of leukemic patient material available for our research. We anticipate that our studies will lead to a more rational approach in the clinic of this highly malignant disorder.
Our research directions:
- Mechanisms involved in HSC self-renewal and hematopoietic lineage commitment
- Interactions between HSCs and their microenvironment, including the immune mivcroenvironment
- Molecular mechanisms underlying the development of acute myeloid leukemia
- Role of epigenetics in normal and leukemic stem cells
- Metabolic heterogeneity in AML
- Immune control over clonal dynamics in AML
- Evaluating immunemodulatory approaches, including anti-tag CAR-Ts, to treat hematological malignancies
- The physics of cancer: coupling the physical properties of leukemic cells to cancer development and therapy resistance