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Despite improvements in outcome for patients with acute lymphoblastic leukemia (ALL), up to 25% of children and 40% of adults fail frontline therapy and their prognosis is dismal, especially for high-risk and relapsed leukemia. Cure rates for ALL patients that are relapsing on therapy is approximately 20% and currently there are no targeted therapies. Dr. Tsirigos' goal is to address this significant clinical need by studying how DNA, our genetic material, is organized inside the nucleus of the cells, i.e. how it is folded in three-dimensional space. Over the past decade, seminal studies have demonstrated that DNA folding is of fundamental importance in that it allows the cell to properly perform its function and retain its identity (e.g. a liver cell versus a blood cell). Very recent studies have demonstrated that disruptions of DNA folding may cause various diseases, such as developmental defects and cancer. However, no study has addressed the question of disruptions of DNA folding on the genome-wide scale in cancer or how such disruptions may be exploited for more effective treatments. Dr. Tsirigos is attempting to answer two key questions. First, are cancer-promoting genes (“oncogenes) capable of disrupting normal DNA folding to transform normal cells into malignant ones? And, second, can drug treatment restore DNA folding and thereby also restore normal cell function?

This grant is made with generous support from the Rally for Ryan Fund. Ryan was diagnosed with high risk ALL when he was 7 years old. He endured 3½ years of treatments with a brave acceptance that this was his fight to win. He recently relapsed and is in the fight again. This fund honors Ryan’s perseverance and his commitment to make a difference for kids with cancer by shaving for St. Baldrick’s and raising funds for research.