Research
Hematopoietic Stem Cell (HSC) Biology and Aging
We conducts 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.
A key area of interest is how aging alters the function and fate of HSCs, resulting in reduced regenerative capacity, increased myeloid bias, and impaired immune output.
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 hierarchy.
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 rejuvenate or protect 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, and ASXL1. This phenomenon underlies clonal hematopoiesis of indeterminate potential (CHIP), a pre-malignant 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 for Acute Myeloid Leukemia
Translating basic discoveries into therapeutic innovation, we actively engage in the design and preclinical development of novel immunotherapies for blood cancers.
One major focus is the development of targeted antibody therapies against CD117 (c-Kit), a surface receptor expressed on leukemic stem cells and healthy HSCs. By engineering high-affinity antibodies and antibody-drug conjugates that selectively deplete malignant cells, the lab aims to improve conditioning regimens for hematopoietic stem cell transplantation and eliminate minimal residual disease.
In parallel, the lab explores adaptive immunotherapies, including the use of chimeric antigen receptor (CAR) T cells and fluoresceinated antibodies that can redirect T cells to tumor antigens with high precision.
These cutting-edge approaches are rigorously tested in humanized mouse models that recapitulate human hematopoiesis and immune responses, enabling the assessment of efficacy, safety, and immune dynamics in a clinically relevant setting.