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.
Despite great progress in treating cancer in children, we are still not able to cure all patients, especially those who relapse or do not respond to standard therapy. In T-cell acute lymphoblastic leukemia (T-ALL), children and adults have poor outcomes because of resistance to existing therapies. Therefore, there is an urgent need to identify new treatment strategies. The term “epigenetics” refers to the environment in the nucleus that is surrounding the DNA in cells and can determine which genes are turned “on” or “off.” The recent discovery that epigenetic changes can contribute to cancer development is key because they may be reversible and targeted with novel anti-cancer drug therapies. Although many tumors have epigenetic alterations, their relevance is not well understood. My research aims to understand epigenetic changes and their consequences in cancer. The research funded by the V Foundation will investigate what causes the epigenetic changes in drug resistant T-ALL. This research holds great promise for revealing new information about the biology of T-ALL and has great potential to bring effective new therapies to patients with this type of blood cancer.
Breast cancer is divided into different categories, called “subtypes”. These subtypes are based on proteins that are present or missing in a patient’s tumor cells that signal them to grow in response to hormones or other factors. This is important because the cancer therapy most likely to be successful is chosen based on the patient’s cancer subtype. Although some subtypes respond to certain drugs, approximately 10 – 20% fall into the “triple-negative” breast cancer (TNBC) subtype, which is one of the most aggressive types of breast cancer. It is difficult to treat and often comes back, even when the initial therapy appears to be effective. This is why we urgently need new ways to treat TNBC. Research findings show that certain signaling proteins, kinases and phosphatases, are often changed in TNBCs. They control cell growth, response to drugs, and cell death. Drugs that target kinases have shown great success in cancer therapy. However, tumors often adapt to them, and these therapies stop working. Using combinations of drugs can overcome this, but it is hard to predict which drugs will work best together. Although kinases have been studied in great detail, less is known about phosphatases and their function as tumors adapt to therapy might help us to better treat TNBC. We have developed a new approach to study phosphatases in tumors and cancer cells. Our analyses will help to determine their role in TNBC, identify new targets for drug development, and improve predictions for combination drug therapies.
Funded by the 2016 Vitale Gala in memory of Julia Mounts.
Rhabdomyosarcoma (RMS) is the most common soft tissue cancer in children. Treatment and survival for children with RMS has not changed for thirty years. Aggressive treatments result in deformities and other health issues in survivors. This highlights a need for more understanding of RMS. Identifying the key features of RMS would guide the search of new treatments. The Pediatric Cancer Genome Project (PCGP) at St. Jude Children’s Research Hospital identified many genetic changes in RMS. The most common subtype of RMS is embryonal rhabdomyosarcoma (ERMS). ERMS had many different genetic changes.
It remains unclear which identified genetic changes drive ERMS formation. Identifying the drivers will expose new targets for treatment. Our lab proposes to identify the essential drivers of ERMS. We will utilize a cell-based approach to explore the genetic changes identified by the PCGP. This system allows us to quickly test the effect of each of the potential driving changes.
We will develop new model systems that more closely resemble our patient’s tumors. Next, we will use these simple models to test new treatments. It is our hope that models with the minimal gene changes necessary for ERMS will simplify our search for new treatments. The result will enable us to pinpoint methods to kill tumor cells. The long-term goal is to couple the specific genetic changes to new therapies.
Ovarian cancers are among the most deadly cancers for women. We need better drugs to treat women with ovarian cancer. Recent studies show that certain ovarian cancers have mutations in unique genes. For example, 60% of epithelial ovarian cancers (EOC) have mutations in the ARID1A gene. This is an important clue to understand EOC and how to treat it. ARID1A mutation forces these cancers to rely on the related protein ARID1B. ARID1B is thus an attractive target for drug discovery. ARID1A and ARID1B are proteins that control gene transcription. However, we do not why ARID1B is vital for ovarian cancers. Using new methods, we will find the genes that ARID1B controls in EOC. We will design a system to eliminate ARID1B in EOC to test if ARID1B is a good drug target. Cancers can often find ways to escape our drugs and come back. We will find loopholes that ovarian cancers use to escape ARID1B elimination. Our goal is to find new strategies to treat women with ARID1A mutant EOC.
Funded by the Stuart Scott Memorial Cancer Research Fund
The human gut contains trillions of bacteria. In fact, there are more bacteria in the gut than there are cells of the human body. To protect the body from gut bacteria, immune cells constantly battle with gut bacteria. This battle occurs inside every person but in some, this battle can cause tumors to grow. Tumors often grow in the colon and this type of cancer, called colorectal cancer, is the location where most gut bacteria dwell. How can the battle with gut bacteria cause colon tumors to grow? To answer this question we must first find out which immune cells control and design the battle plan. We think that the battle plan against gut bacteria is designed by a special immune cell, the dendritic cell. There are many different types of dendritic cells and we found that each has a different battle plan. We want to find out which dendritic cells enter colon tumors, which dendritic cell’s battle plan cause tumors to grow, and which battle plan may help fight the tumor. When colon tumors grow we think that gut bacteria force the dendritic cell to make proteins that shield the tumor from attack and help the tumor to grow. We are testing these ideas by changing how dendritic cells respond to gut bacteria, to find out how this changes the battle plan, and to discover how this impacts colon cancer.
The spread of cells from one organ to another organ is the main cause of death for cancer patients. When cancer cells continue to grow and form a tumor some of them run out of oxygen. Cancer cells learn to deal with these low levels of oxygen by switching on genes that help them survive even under stress. As a result, rather than dying these oxygen-deprived cells become even more powerful and can continue to survive even when treated with cancer drugs. To investigate how these cells function we must find these powerful cells within a tumor. To do this we designed a trick to make the cells change color when they do not have enough oxygen. We can use this color to find and collect the cells from within a tumor. Once we collect the cells, we will try to determine what makes them so powerful and use this information to try to design methods to kill these deadly cells.
Funded by Hooters of America, LLC., in memory of Kelly Jo Dowd
Each breast tumor contains a unique set of genetic mutations that contribute to tumor growth and response to treatment. This means that each patient will respond differently to specific anti-cancer drugs. Triple negative breast cancers are an aggressive and deadly form of breast cancer. Treatments used for this disease often do not work and may have harmful side-effects. As such, there is a need to understand what causes these tumors. This knowledge will allow new therapies to be developed to improve breast cancer treatment. One such opportunity involves what is known as the PI3K/Akt pathway inside cells. This pathway is present in triple negative breast cancer and carries messages within the cell to drive various cell functions including cell growth and survival. When the PI3K/Akt pathway is active in other forms of cancer, it often responds to targeted drugs but not in triple negative breast cancer. These drugs may not work because few mutations are present in genes that are known to regulate this pathway. The goal of our research is to understand what regulates PI3K/Akt messaging in triple negative breast cancer. We propose to identify essential genetic alterations and determine how these genes might impact PI3K/Akt messaging and breast cancer. The proposed studies will result in a better understanding of PI3K/Akt signaling and serve as the foundation for personalized breast cancer treatment.
Funded by Hooters of America, LLC., in memory of Kelly Jo Dowd
In humans, an early age of first pregnancy reduces the risk of breast cancer by an incredible 30%. The effects or pregnancy on reducing breast cancer risk is present in multiple mammalian species, and confers a long-lasting cancer protection. However, we know little about the modifications that confers breast cells with a cancer resistant state. The goal of our proposal is to understand pregnancy-induced breast cancer protection and to discovery how to manipulate its effects. Our ultimate goal is to devise preventive strategies to mimic the preventive effects of pregnancy and potentially reduces breast cancer occurrence.
Blood cancer affects thousands of individuals each year, and despite impressive early therapeutic advances, cure rates for most blood cancers have reached a plateau. Moreover, most therapies that are currently used do not specifically target blood cancer cells and therefore lead to undesirable side effects in a large number of patients. There is therefore an urgent need for developing safer new drugs for this devastating disease. The focus of this research proposal is to define the molecular mechanisms of a specific sub-type of acute myeloid leukemia that mostly affects children and young adults but is also seen in older patients. In this project, we will make use of molecular, genetic and biochemical methods to identify ways and means by which genes that are mis-regulated in these tumors lead to cancer development. Based on our preliminary findings, we propose that our approach may lead not only to a more detailed understanding of this specific sub-type of blood cancer, but also to novel treatment strategies.
Funded by the Stuart Scott Memorial Cancer Research Fund
Cancer rates are falling in North America, with a few important exceptions. Liver and endometrial cancers in African Americans and Hispanics continue to rise. We try to decrease that disparity by identifying new characteristics of those cancers. Those characteristics allow doctors to determine if a patient will respond to new therapies. The characteristics also provide an incentive for drug companies to pursue new therapies, since the clinical trials are more likely to succeed.
But how do we find these characteristics? Why have they not already been discovered? The answer is that our lab made a new discovery about how these cancers grow. We found that a protein controls organ growth by placing a “molecular barcode” on the DNA. Under healthy conditions, this barcode is only present when an organ is supposed to grow. But in cancer the barcode is always present, commanding it to grow into a tumor.
The work we will do here tests if we can examine mouse liver tumors for these barcodes. The barcodes will allow us to develop new therapies for liver cancer patients. Those new therapies should stop tumor growth. The barcodes also provide a way for doctors to know which drugs will work for a particular patient. By personalizing medicine, we hope to make new and better therapies that are not worse than the disease.
