Our goal is to identify how blood stem cells are regulated and how these processes can be hijacked during stress and disease. We test stem cell function at the molecular, cellular, microenvironmental and organismal scales.

Our understanding of hematopoietic cell function has been predominantly based on transcriptional and protein activity programs. The contribution of sugars, or glycans, to hematopoietic cell function, has yet to be clearly defined. In the Termini Lab, we evaluate how proteins and glycans synergize to regulate hematopoietic cell fate during homeostasis and in response to stress.

Hematopoietic stem cells have extraordinary regenerative ability and are used clinically to treat patients with hematological malignancies and immune disorders and to supplement the treatment of patients with solid tumors. In the Termini Lab, we assess the intrinsic properties that mediate hematopoietic cell function. Furthermore, we will identify how radiation, chemotherapy, and disease remodel hematopoietic cells to ultimately develop novel cancer therapies. 

Our Projects

Molecular organization and hematopoietic stem cell fate

Hematopoietic stem cells require carefully coordinated growth factor signaling to balance their self-renewal and regenerative capacity. To maintain this balance, interactions between growth factors and their cognate receptors must be regulated in space and time. For example, it may be advantageous to limit growth factor binding to a receptor to promote sustained signaling, while in other contexts encouraging receptor binding may be necessary for a quick response to a stressor. This project will take a unique approach by bridging super-resolution microscopy with hematopoietic cell analyses to paint a molecular portrait of how the physical arrangement of growth factors and receptors mediates hematopoietic stem cell fate decisions. 

Hematologic regeneration and the microenvironment

While necessary for many cancer treatments, cytotoxic insults, including radiation and chemotherapy, significantly influence hematopoietic stem cells and their microenvironment, or niche. For example, after injury, the bone marrow becomes significantly remodeled with regard to the cellular and macromolecular composition. In this project, we aim to understand how niche reorganization influences hematopoietic function. This project will take a unique approach by combining proteomics with high-resolution 3-dimensional analyses of the bone marrow microenvironment to understand how hematopoietic regeneration is coordinated. 

Adult and pediatric leukemia development and targeting 

Much of what we know about normal hematopoiesis and hematopoietic stem cells has informed our understanding of hematological malignancies and leukemia stem cells. Chemotherapy is used to control leukemia cell growth, but residual chemotherapy cells that are resistant to standard treatments can initiate disease relapse. Furthermore, these chemoresistant cells express distinct molecular programs unique from unperturbed leukemia cells. The goal of this project is to understand how leukemia cells adapt to chemotherapy to identify vulnerabilities that can be targeted during treatment. We currently focus on adult and pediatric acute myeloid leukemia.