Welcome to the laboratory of James Thompson, MD in the Departments of Medicine and Immunology. The research interests of the lab include:

• etiology of the myelodysplastic syndromes (MDS) and unexplained anemia (UA) of aging
• the role of mtDNA mutations in the development of MDS and UA
• the role of mitochondrial DNA (mtDNA) mutations in immunosenescence For inquiries about student, post doc or other research positions, please contact us by email.

I. Myelodysplastic Syndromes (MDS) and Unexplained Anemia (UA)
The myelodysplastic syndromes are a heterogeneous group of age-related bone marrow failure disorders. Although what we call “MDS” is undoubtedly a cluster of related disorders with different causes, these disorders share the following features:

• cytopenias (low blood counts)
• dysplastic (morphologically abnormal) hematopoietic development
• persistence in the bone marrow over years to decades
• an increased rate of apoptosis in the bone marrow
• impaired in vitro growth using standard tissue culture conditions A fundamental goal of the lab is to understand how a disorder that demonstrates self-renewal characteristics suggestive of a stem cell origin nevertheless shows such a predisposition to cell death in differentiating cells. We have previously demonstrated that hematopoietic progenitors cells from MDS patients are particularly sensitive to increased oxygen tension (Thompson et al., 2007), suggesting that mitochondrial dysfunction may play a role in these disorders.

II. Mitochondrial DNA (mtDNA) mutations in MDS and UA
Our data describing extreme oxygen sensitivity of MDS progenitors, as well as work from other labs demonstrating the presence of mtDNA mutations in the marrow of some MDS patients, led us to explore the anemia reported in a murine model of premature aging due to accelerated mutation of mtDNA. We recently demonstrated that these mice develop many of the hallmarks of human MDS, including a progressive and ultimately lethal cell-intrinsic megaloblastic anemia (Chen et al., 2009). The further exploration of the mechanisms linking mitochondrial dysfunction to MDS and UA are a major focus of current efforts in the lab.

III. Mitochondrial DNA (mtDNA) mutations in immunosenescence
In addition to megaloblastic anemia, our mitochondrial mutator mice also develop profound defects in both B- and T-lymphopoiesis, paralleling findings seen in both human MDS as well as in immunosenescence during normal human aging. Given our location within the Department of Immunology, we are exploring a number of collaborative efforts to characterize these defects in greater detail.