Our Current Projects
Utilizing epigenetic profiling tools to better understand and treat pediatric cancers
Our primary focus here at the Sarthy Lab is examining whether epigenetics might play a role in how lymphomas start and why they sometimes evade treatment. Dr. Sarthy explains epigenetics in these terms: If the genome is a book, genes are the words and epigenetics is the spacing between the words. In many adult cancers, the words have typos, helping explain why these cancers happen. In pediatric cancers, the words are almost always spelled correctly, but, as Dr. Sarthy’s previous work helps demonstrate, the spacing between the words is often way off. This could help explain why these cancers happen and provide a possible target for treatment.
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The Sarthy Lab is working to understand whether it’s possible to use small molecules to fix the spacing, or to make the spacing worse to destroy cancerous cells. We employ tools including enzyme tethering and genetic sequencing in order to map chromatin features across the genome to explore our research questions.
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01
How do certain molecules that interact with DNA impact cancers?
The Sarthy Lab is exploring how a specific DNA-binding protein plays a role in lymphomas. This protein, called H2A.B, is normally expressed only in developing sperm cells. Our previous work has identified abnormal expression of this protein in several types of cancer including lymphomas but not in other healthy cells in the body. We are now trying to understand how this protein alters the DNA of lymphoma cells to cause cancer and identify new strategies for targeting this protein.
In addition, we are examining whether broad epigenetic diversity enables some cancer cells to evade treatment or relapse after treatment. Our team is taking samples from people whose cancers have come back and comparing them to their initial cancers. This enables us to examine epigenetic differences between the two. We hypothesize that the sperm protein is driving epigenetic differences and allowing cells to evade therapy. This research will also help answer a larger question of whether epigenetic diversity is the reason that some cancer cells can evade therapy.
02
What makes the deadliest cancers so difficult to treat?
The Sarthy Lab is also working to understand if specific epigenetic profiles make certain cancers particularly deadly. Our research team is examining the epigenome in samples from patients and model organisms with high-risk leukemia, sarcoma, and pediatric and adult glioblastoma. The goal is to understand common features and differences that make certain cancers unique or particularly difficult to treat.
Are there less toxic chemotherapy drugs which can effectively treat pediatric cancers?
More children than ever are surviving cancer. But many of them live with long-term side effects of treatment, including heart problems, infertility, and secondary cancers. At the Sarthy Lab, we are examining whether a chemotherapy drug called aclarubicin might be effective against pediatric lymphomas and other childhood cancers while resulting in fewer side effects than the current standard of care.
This therapy is commonly used in Asia to treat elderly cancer patients. It is often given to people who have heart problems because they are unable to tolerate more toxic chemotherapy drugs. If this therapy proves effective in children, it could be quickly implemented as a new treatment option because it has already been widely used and proven safe in other countries.