OVERVIEW

Our goal is to understand how the blood system works in health and disease. We are studying human stem cells because there are important differences between mouse and human stem cells. To study blood stem cells, known as hematopoietic stem cells or HSCs, we are using umbilical cord blood and induced pluripotent stem cells (iPSCs). These stem cells can differentiate into all blood cells which carry oxygen, carry out blood clotting, and participate in innate and adaptive immune responses.

 

Primary human cells are in short supply, so we use induced pluripotent stem cells (iPSCs) as an alternative source. iPSCs can be created from any cell by a method called ‘reprogramming’ and can differentiate into any cell type in the body, such as neurons, cardiac muscle, and blood. We are looking for ways to instruct iPSCs to become blood stem cells, so that every person who needs a marrow transplant can get one from her or his own cells.

 

Just as iPSCs from healthy individuals can be used to create healthy matched blood cells, iPSCs from patients with blood disorders make diseased blood cells. We can collect bone marrow cells from patients, but there are often too few of these cells to help us understand what goes wrong in these diseases. We are using iPSCs from patients with blood disorders to uncover causes of these diseases and to discover candidate therapeutics using high-throughput drug screens. We hope to find cures for inherited bone marrow failure disorders, including Diamond Blackfan anemia, and acquired myelodysplastic syndromes.

CURRENT PROJECTS

1. Clonal evolution of myeloid neoplasms. We are using genomics and iPSC reprogramming to uncover early clonal history of myelodysplastic syndromes (MDS) and myeloid leukemias (AML).

 

2. Disease modeling of myelodysplastic syndromes. By differentiating patient iPSCs into hematopoietic progenitors, we are studying disease mechanisms in specific subtypes of MDS and AML.

 

3. Role of autophagy in human hematopoiesis. Autophagy and mitophagy are critical metabolic pathways for cell homeostasis. We are studying how these pathways are dynamically regulated in HSCs and hematopoietic differentiation.

 

4. Generation of HSCs and RBCs from iPSCs. We are overcoming barriers to HSC development from pluripotent stem cells. We are also using iPSCs as a source of clinically valuable red blood cells for transfusion in sickle cell disease.