Funded by Bristol Myers Squibb
We study the response of the immune system to cancer. A type of immune cells, called T cells, play a central role in killing and clearing cancer cells. However, as cancer develops, these cells malfunction, leading to their inability to clear cancer cells, allowing for them to grow out of control. Many therapies used to treat cancer now target those cells, working to enhance their ability to fight cancer cells. One of them is called PD-1 blockade treatment. However, there is much we do not know about this treatment. Due to this, there are many individuals where this therapy does not show any therapeutic effect over traditional cancer treatments. We previously have found that the means by which the immune cells fuel their energy stores (called glucose metabolism) is central to their overall function during cancer development. Some tumors consume many resources to grow as quickly as possible, this prevents immune cells in the area from using these same resources to fuel energy from glucose. Our overarching goal is to determine the mechanism by which these immune cells malfunction due to a lack of resources and how this insufficient level of resources hinders the immune cell response to cancer. The research completed will be instrumental in our understanding of how T cells respond to cancer cells during the progression of disease and treatment.
Funded by Hooters of America, LLC
Age is the greatest risk factor for breast cancer. About 80% of all breast cancers occur in women older than age 50. Aging is associated with tissue changes as well as changes in the genes that are expressed in breast cells. However, the age-related molecular and cellular mechanisms that underlie these changes and contribute to breast cancer development remains poorly understood. Our lab studies a mechanism by which genes are read to produce different proteins, called RNA splicing. RNA splicing can generate proteins with different functions from a single gene. We previously discovered that this process is altered in human tumors and leads to breast cancer. Additionally, changes in RNA splicing also occur in healthy aging. Here we will test the hypothesis that (1) changes in RNA splicing occur in the mammary tissue with age, and (2) that these splicing changes prime the breast for tumor formation. Our research findings may provide biomarkers of breast cancer risk before the tumor develops. Our ultimate goal is to identify novel strategies for early breast cancer detection, early intervention, and prevention.
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.
Funded by the Hearst Foundation
Acute myeloid leukemia (AML) is an aggressive blood cancer where <30% of all patients are long-term survivors and >11,000 patients die per year in the United States alone. Treatment of AML has changed little in the past two decades, and is ineffective in curing patients of their disease, as the majority will relapse within five years.
Doctors and scientists recently investigated the DNA of AML patients and found that many patients contain mutations in a gene called DNA methyltransferase 3A (DNMT3A). Strikingly, many healthy adults also have DNMT3A mutations in their blood cells. This suggests that additional mutations (not just DNMT3A alone) are required to develop AML. Currently, scientists and doctors have a poor understanding of why and how mutations in DNMT3A frequently, but not always, lead to the development of blood cancer. This is important to understand for two reasons. First, to develop new ways to assess risk of AML in healthy people with DNMT3A mutations. Second, to create new therapies that stop DNMT3A-mutant cells from causing AML to recur after treatment.
Our work focuses on the initial changes that drive cancer development or relapse. Therefore, we cannot directly use AML patients samples that already contain many mutations. I propose to use new mouse models precisely engineered to carry mutations found in human AML patients. My research will use these models to show why and how AML develops from mutations in DNMT3A.