Cancer has traditionally been thought of as a disease driven by DNA mutations that result in abnormally growing cells that interfere with the body’s normal functions. However, we now appreciate that cancer can be driven by processes that do not change the DNA code itself, but rather alter the accessibility of the DNA and how it’s used to produce proteins. In different types of tumors, cancer cells can block access to certain sections of DNA, such as those where there are genes that might otherwise transmit signals that inhibit cancer formation. In these cases, treatment with drugs called DNA hypomethylating agents (HMAs) prevents this block in order to re-initiate these signals and prevent tumor formation. In other cases, cancer cells with mutations in the DNMT3A gene have “open” sections of DNA that should normally be “closed”—which can promote tumor growth.
These genetic alterations can also interfere with immune cells and their activity. Therefore, Dr. Colleen Lau aims to better understand how these HMAs and the lack of DNMT3A affects immune cells and their ability to kill cancer cells. Not only will she test the function of these immune cells, she will also generate global maps of DNA accessibility and inaccessibility in order to pinpoint potential regions that are actively regulated. Through these studies, Lau hopes to uncover more opportunities for improving the effectiveness of HMAs and developing strategies to better combat cancers that harbor DNMT3A mutations.
Projects and Grants
Investigating the role of DNA methylation on NK cell-mediated tumor immunity
Memorial Sloan Kettering Cancer Center | All Cancers | 2019 | Joseph C. Sun, Ph.D.
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