Ewelina Bolcun-Filas, Ph.D.

Funded in partership with WWE in honor of Connor’s Cure

Young girls who survive cancer may also face the devastating prospect of reduced fertility and hormonal problems when they reach adulthood. Treatment of pediatric cancer damages ovaries and lifetime egg supplies in up to 20% of young girls. Current strategies to correct loss of fertility involve removal of eggs from patients prior to treatment, but this is invasive and does not prevent the chronic health problems that result from ovarian damage.

To improve quality of life for young female cancer survivors, we must develop strategies to protect their egg supplies, which are critical for continuous endocrine function of ovaries and fertility. Our goal is to identify egg-saving treatments that can be used along with standard cancer therapies.

We will begin by analyzing how eggs and other cells in the ovary respond to different cancer treatments. By detecting changes in the levels of proteins in response to various cancer therapies, we can learn which proteins are responsible for egg death and identify drugs that target those proteins to prevent eggs from dying.

Our lab has previously found that a specific protein, CHK2, promotes elimination of eggs in response to the kind of damage caused by cancer treatments, making this a promising target. We will test the feasibility of targeting CHK2, and we expect that our work will demonstrate the benefits and potential risks of CHK2-targeting drugs for protecting eggs. We also expect to provide a list of novel drug targets for egg protection in cancer patients.

Michael Birnbaum, Ph.D.

Scientists have recently made tremendous progress in treating cancers by activating the immune system to attack the tumor. However, these therapies are not effective against cancers with less DNA damage due to insufficient anti-tumor immune responses. The immune system is capable of attacking these tumors, but suppressive immune subtypes such as regulatory T cells (Tregs) are coopted by the tumor to protect itself. Tregs are associated with poor survival in many cancers, and show enrichment for particular T cell receptors (TCR). The TCR senses targets by binding to their peptide-MHC ligands, which display a cross-section of peptides expressed by a particular cell. Despite their important role in protecting tumors, the identity and specificity of tumor-resident Tregs is poorly studied.  We are working to profile what T cells are enriched in low mutation rate cancers. We can then use approaches we have developed to find what these T cells as seeing in the tumor. This information will help us understand of one of the most important tumor-protective cell types, and may open the door to new cancer immunotherapies.  

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