Meet Our Researchers


Associate Member, Broad Institute of MIT and Harvard
Physician Scientist and Instructor in Medicine, Dana-Farber Cancer Institute

Zuzana Tothova is a medical oncologist at the Dana-Farber Cancer Institute. Her research focuses on blood cancers, a group of cancers including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Project Description

MDS affects 30,000 new people each year in the U.S., and its long-term survival rate is less than 5 percent. About 11 percent of MDS patients have mutations in a protein complex called the cohesion complex, which plays an essential role in regulating cell division. Zuzana plans to investigate how cohesin mutations affect a process called DNA looping. Her hypothesis is that malfunctions in DNA looping lead to the development of MDS and other blood diseases.

The Question

My overarching hypothesis is that aberrant DNA looping leads to the development of AML, MDS, and other blood diseases. In healthy DNA looping, cohesin acts like a lasso, bringing together disparate regions of the genome. But if cohesin is mutated—as it is in many blood cancers—that lasso never gets formed or it forms in the wrong place. My team will investigate changes in DNA looping as the disease progresses from one state to the next, with the aim of answering one large question: How, mechanistically, do malfunctions in DNA looping affect gene expression and the development of blood cancers?

The Approach

I will use my BroadIgnite grant to analyze the chromatin—the complex of DNA, RNA, and proteins that help package our genetic material into chromosomes—in samples from patients at various stages of these blood cancers, who are being treated at the Dana-Farber Cancer Institute. We believe the data that emerges from this study will paint a clearer picture of the role of DNA looping in blood cancers—and shed light on novel mechanisms that we can target therapeutically.