Research
Hematopoietic Stem Cell (HSC) Biology and Aging
We conduct foundational research into the biology of hematopoietic stem and progenitor cells (HSPCs), focusing on the molecular and cellular mechanisms that regulate their self-renewal, differentiation, and maintenance across the lifespan of the individual.
A key area of interest is how aging alters the function and fate of HSCs, resulting in reduced regenerative capacity, increased myeloid bias, impaired adaptive immune cell output, and increased clonal dominance and malignant transformation.
By employing high-resolution single-cell analyses, in vivo lineage tracing, and genetically engineered mouse models, the lab dissects the impact of age-associated changes on the hematopoietic and immune system.
This work provides critical insights into why the elderly are more susceptible to bone marrow failure, anemia, immune dysfunction, and hematologic malignancies, and informs strategies to protect or rejuvenate the stem cell compartment.
Inflammation and Clonal Hematopoiesis
A major research axis of the lab centers on the intersection of inflammation, innate immune signaling, and clonal evolution in the hematopoietic system.
Chronic inflammatory stimuli—such as those derived from infections, microbiota dysregulation, or sterile inflammation—have profound effects on HSC behavior, often triggering proliferation, differentiation, and exhaustion.
We demonstrated that specific inflammatory signals, such as IL-1 and TLR-TRIF pathways, create a selective environment that promotes the expansion of HSPCs harboring mutations in genes like TET2, DNMT3A. This phenomenon underlies clonal hematopoiesis of indeterminate potential (CHIP), a pre-malignant hematopoietic state associated with aging and increased cardiovascular and cancer risk.
By modeling these processes in mice and studying human samples, the lab seeks to unravel how inflammatory stressors reshape the hematopoietic landscape and pave the way for leukemogenesis.
Immunotherapies against Stem Cell Malignancies
Translating basic discoveries into therapeutic innovation, we engage in the design and preclinical development of novel immunotherapeutic approaches against blood cancers.
A major focus is the development of engineered therapies against surface antigens expressed on leukemic stem cells and healthy HSCs. This includes the generation of CAR T-cells and immune cell engaging antibody constructs, such as bispecific T-cell engagers (TCE). With this the lab aims to eliminate minimal residual disease and at the same time improve conditioning regimens for hematopoietic stem cell transplantation.
Furthermore, by developing platform technologies, we extend our efforts to use immunotherapy approaches also against solid organ neoplasia.