Characterization and Targeting of Chromatin Dysfunction in Pediatric Cancers
Mentor Name: Jay Sarthy
The Sarthy Lab has found that a DNA-binding histone protein called H2A.B that is normally expressed in sperm cells is accidentally turned on in many pediatric and young adult cancers, and in particular lymphomas and leukemias, and that this protein is very important for cancer cell growth. Proteins that are very important for normal development can be inappropriately hijacked to promote diseases including cancer. Our initial work shows that this histone protein changes the way the cell decodes its own DNA, allowing cancer cells to grow and spread more quickly. We are studying how this testis histone exerts its effects and are testing whether a chemotherapy drug widely available in Asai that prevents histones from binding DNA is effective in treating these cancers. As this agent, Aclarubicin, is affordable, easy to administer and safer than its cousins doxorubicin and daunorubicin, we anticipate that incorporation of this agent into treatment regimens for H2A.B-positive cancers will dramatically improve current regimens efficacy and toxicity profiles, sparing children the long-term effects of harsh chemotherapies
