Markus G. Manz Laboratory
Our research is focused on the biology of hematopoietic stem and progenitor cells, homeostasis of hematopoiesis in steady-state and under environmental stress, and the pathogenesis of hematopoietic stem and progenitor cell derived malignancies.
Our goal is to develop innovative therapeutic strategies, including small molecules and engineered immunotherapies, to foster healthy aging and improve treatment outcomes for hematopoietic stem and progenitor cell derived diseases such as acute myeloid leukemia and myelodysplastic neoplasia.
Understanding the Hematopoietic System and Treating its Malignancies
Hematopoietic Stem Cell (HSC) Biology and Aging
We investigate how hematopoietic stem and progenitor cells (HSPCs) function and change over time. We focus on how aging affects the factors governing HSC self-renewal, changing its lineage commitment or bone marrow microenvironment interactions, leading to reduced immune output, myeloid bias or stem cell exhaustion.
These insights help explain the increased incidence of blood disorders and immunodeficiency in older individuals.
Inflammation and Clonal Hematopoiesis
A core focus of the lab is understanding how chronic inflammation shapes the hematopoietic system and drives clonal expansion of mutant HSCs.
We have shown that cytokines like IL-1 and signaling through Toll-like receptors promote selective growth of mutated clones (e.g., TET2), contributing to clonal hematopoiesis of indeterminate potential (CHIP) and increasing the risk of leukemia and cardiovascular disease.
Immunotherapy for Hematologic Malignancies
The lab develops novel immunotherapies for blood cancers, including antibody or CAR-T cell based strategies targeting both leukemic stem cells and HSPCs, allowing for complete eradication of tumor cells and facilitated conditioning regimens.
These preclinical therapies and platforms are tested toughrougly in home to fully control blood cancers, and possibly extend their applications to solid organ neoplasia.
Interested in joining the lab?
To achieve progress together, we're always looking for dedicated students and researchers!