Hematopoiesis maintains a life-long supply of the entire spectrum of highly specialized blood cells dependent on systemic needs. This process relies on a tightly regulated balance of self-renewal, commitment, and differentiation of a small number of pluripotent hematopoietic stem cells (HSC).
Recent experimental evidence has shown that acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) arise from an unexpectedly diverse pool of pre-leukemic stem cells (pre-LSC), preceding the formation of fully transformed leukemia stem cells (LSC). Pre-LSC as well as LSC are characterized by a relative resistance to chemotherapy and thereby contribute to treatment failure. Defining the molecular characteristics and mechanisms in pre-LSC and their progression to fully transformed LSC is critical to understanding the genesis of leukemia and to developing therapeutic strategies by which these processes can be targeted.
The goal of our research is to delineate critical mechanisms in HSC that drive formation and function of pre-LSC and LSC. We are studying murine genetic models as well as primary human samples from patients with MDS and leukemia. Our studies aim at the development of targeted, pre-LSC- and LSC-directed therapies, which could ultimately also be employed for precision prevention of relapse/progression, or "cancer interception".
In our lab, we investigate how pre-leukemic stem cells (pre-LSCs) drive the development and progression of leukemia. By integrating genetic mouse models, single-cell analysis of patient samples, and computational approaches, we uncover the clonal diversity and resilience of pre-LSCs. Our goal is to identify early molecular events that can be targeted to prevent leukemic transformation and improve therapeutic outcomes.
In our lab, we apply glycan-based profiling to uncover hidden functional diversity among hematopoietic stem and progenitor cells. Using HS-specific single-chain antibodies, we identify distinct subpopulations not resolvable by conventional CD markers alone. This approach reveals glycan signatures that correlate with transcriptional states and lineage potentials, offering new strategies to refine stem cell classification and function.
We use single-molecule imaging and transcriptomic approaches to dissect heterogeneity and transcriptional plasticity in hematopoietic stem and progenitor cells. By tracking individual mRNA and transcription factor dynamics, we uncover how unique transcriptional states emerge, evolve, and drive drug resistance or leukemia progression. These insights allow us to map stem cell fate decisions at unprecedented resolution and understand how non-genetic mechanisms contribute to relapse and treatment failure in AML.
We are investigating how extrinsic factors within the microenvironment regulate leukemic stem cell behavior. Using spatially controlled 3D bioprinting and in vivo xenograft models, we aim to uncover how cell-cell interactions and cytokines such as IL-8, which lacks a murine homolog, contribute to leukemogenesis. Our lab is developing IL-8-expressing mouse models to better understand its role in myeloid malignancies and enable mechanistic studies that were previously limited by species-specific constraints.
