Designed to identify, retain and further the careers of talented young investigators. Provides funds directly to scientists developing their own independent laboratory research projects. These grants enable talented young scientists to establish their laboratories and gain a competitive edge necessary to earn additional funding from other sources. The V Scholars determine how to best use the funds in their research projects. The grants are $200,000, two-year commitments.
New drugs that use the body’s own immune system to treat cancer have been one of the most exciting recent developments in cancer research. Studying the cancer cells in a tumor tells doctors a lot about how to treat that kind of cancer, no matter whether it appears in the breast, the brain or somewhere else in the body. Most types of cancer that respond to these new drugs have something in common: they tend to have high numbers of gene mutations, or DNA changes. Mutations sometimes cause changes that make the tumor cell look like it has been infected by a virus or bacteria. This makes the immune system attack the tumor, just as it would attack a cold or an infected cut on the finger. Most mutations have no impact on how aggressive a patient’s cancer is, so having more mutations is not a bad thing. In fact, patients whose tumors have more mutations often have better outcomes, probably because they trigger the immune system to start attacking the cancer. Unfortunately, many other cancer types have fewer mutations, and so may not respond as well to new drugs that stimulate the immune system. We suspect that a specific group of drugs may make some of these tumors respond better. In this study, we will try to find out if this is true. If so, it may be possible to begin testing the drugs on patients right away to help patients whose cancer does not respond to standard treatments.
Following surgery and treatment, breast cancer patients live with a high risk of developing a relapse. When tumors do recur, especially at distant sites, they are often incurable. Therefore, it is important to develop new approaches for preventing breast cancer relapse. The period between treatment of the primary tumor and the formation of a recurrent tumor is called dormancy. During this stage there are cancer cells somewhere in the patient’s body that are dormant, or not actively growing. These dormant cells are the source from which recurrences must arise. Understanding how these cells survive for long periods and designing ways to kill them is important for preventing recurrences.
Dormant tumors cannot be detected by current imaging methods, and so studying these cells in patients is difficult. We have developed mouse models that allow us to study dormancy and recurrence. Using these models, we have found that dormant tumors have a unique type of metabolism. In order to translate this finding to a potential therapy it is important to know more about this metabolism works, and whether dormant cells can be killed by targeting this metabolism. In this proposal we will use the mouse models we developed to address these questions. Once we understand more about dormant cell metabolism, we may be able to design drugs that can kill dormant cells and prevent breast cancer relapse.
Acute myeloid leukemia (AML) is a deadly blood cancer. Three of four patients with AML die within five years. Those who survive suffer harsh side effects from treatment. This problem has not changed in 30 years. We need to create new treatments that can cure AML before the disease becomes too hard to control. To do this, we need to learn what causes AML cells to grow in the body.
We now know that cancers grow not only because of changes in the cancer cells themselves, but also because of signals released by nearby healthy cells. Our lab found that an inflammation-causing protein called IL-1B plays a key role in AML by: 1) encouraging growth of AML cells, 2) stopping growth of normal cells around a tumor, and 3) preventing the body’s immune system from killing AML cells when cancer cells are growing. We will explore how to stop AML’s growth by blocking the communication between AML cells and this IL-1B signal. Blocking this signal could also allow the body’s natural defenses to recognize and kill AML cells. Our goal is to find new drugs to improve treatment and quality of life for AML patients.
Gliomas are aggressive brain tumors. Gliomas are very heterogeneous, which is a big problem for treatment. Traditionally, researchers have profiled pieces of tumor with a lot of cells all mixed together, thus masking many information differences. To precisely define brain tumors, I propose to use single cell sequencing techniques directly in patient samples. My laboratory is a leader in these techniques and has shown the potential of these approaches in cancer. I thus propose to: (aim1) perform single cell analyses in brain tumors in adults and children. I also propose (aim2) to use our new data to identify novel ways to target specific programs in brain tumors. Our research will provide the community with a very detailed view of gliomas and suggest ways to improve the treatment of patients.
Acute lymphoblastic leukemia is one of the most common and deadly childhood cancers. Drugs that children are given often do not fully kill all of the leukemia cells. A specialized cell, called a leukemia stem cell, preserves the leukemia through selfrenewal. If one leukemia stem cell persists, the cancer can regrow and make a child sick. Our goal is to find better ways to kill these cells so that we can cure patients. One way that we do this is by studying leukemia stem cells in a zebrafish cancer model, which is very similar to human disease. Here, we will use a new method to find genes that are only expressed by leukemia stem cells. We will then look for drugs that target these genes and can kill leukemia stem cells. The breakthroughs that we make can be quickly applied to human disease because our studies are being done in an animal model. Our research will give vital data about leukemia stem cells and biology, and we hope we will discover new drugs to treat leukemia.
