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.
Cancer treatment is being improved by ever more specific drugs. But, there is growing proof that cancers growing in different parts of the body do not react to the same drugs, even if the tumor has the same mutation. For example, a lung tumor may respond when given a drug, but a tumor with the same mutation from another part of the body may not react in the same way. Some lung tumors can look a lot like healthy lung tissue, but some look like a completely different tissue. My lab has developed a mouse model of lung cancer that lets us change the state of the tumor from looking like one from the lungs to the stomach. We have shown that this change can happen in human lung cancer too. We will see if this change affects how lung tumors respond to targeted therapy. We will then use this knowledge to improve lung cancer treatment.
Prostate cancer is a common cause of death among men. Current treatment includes hormone therapy that targets the androgen receptor (AR). The AR promotes the growth of prostate cancer. Unfortunately, prostate cancer cells remain resistant to current therapy. This is partly due to the formation of active forms of AR. We need to understand how active forms of AR arise. Thus, we can discover therapies that will not become resistant to treatment. The JMJD1A protein plays an important role in this process. In this study we will look at how JMJD1A promotes the generation of active AR forms. JMJD1A may regulate several other proteins (e.g. HUWE1, c-Myc and HNRNPA1) to do this. We will block the expression of these proteins to see if prostate cancer cells become sensitive to hormone therapy. Our experiments include cell culture and mouse tumor models. Our study will stimulate the interest to develop inhibitors that block the activity of JMJD1A or the proteins it regulates. The inhibitors will serve as effective therapies for prostate cancer.
Pancreatic cancer is a very aggressive disease. It is the 4th leading cause of cancer deaths in the USA. Only 6% of patients who can undergo surgery will survive past five years. Late diagnosis and lack of good treatment options are some of the reasons for this outcome. Recent progress in cancer immune therapy showed effect in cancers such as relapsed leukemia and metastatic melanoma. Unfortunately, immune therapy was not effective in patients with pancreatic cancer. One explanation for this result is that pancreatic cancer blocks immune responses against cancer. Thus, understanding how cancer promotes immune suppression is vital to our ability to treat this deadly disease. Our initial work has revealed that B cells promote growth of pancreatic cancer. However, it is not clear how B cells promote cancer growth, and how targeting these cells can benefit patients. We propose to understand how B cells function in pancreatic cancer. The goal of this research project is to find new targets that can block immune suppression in pancreatic cancer. Using both mouse models of pancreatic cancer and patient samples, we hope to identify B cell based targets in pancreatic cancer. We ultimately hope to translate our findings into effective therapies that may also work with existing immune therapy treatments.
2016 V Foundation Wine Celebration Volunteer Grant
in honor of Pack and Susan and Sheryl Warfield
EBV infects over 90% of the population. It causes infectious mononucleosis (“mono”) among adolescents and 200,000 cancer cases worldwide every year. People infected by EBV may develop Burkitt lymphoma, a disfiguring disease common in children in Africa, Hodgkin lymphoma, head-and-neck cancer, and stomach cancer. EBV infection is typically mild but the virus remains in the body. It can become active again and cause disease in people with a weakened immune system, such as transplant or AIDS patients. Diagnosis and treatment of cancer related to EBV infection can be difficult. Even though we have known EBV causes cancer in humans since 1965, no vaccine exists. Scientists agree on the urgent need to develop one. Our goal is to develop a safe and effective vaccine to prevent and cure EBV-driven cancers. We will develop a vaccine using virus-like particles (VLPs). When a person receives the VLP-vaccine before EBV infection, the body will prepare itself to fight infections with antibodies. Also, immune cells will be ready to identify and kill cancer cells hiding EBV. We know our VLP-vaccine works in mice. We will repeat our work in an improved mouse model that has human immune cells. We predict that VLP-vaccine will cause antibodies to be made and will prepare immune cells to fight EBV infection and cancer cells. If successful, we will test the vaccine in healthy patients to prove its safety. Then, clinical trials in EBV-infected patients will test if the vaccine works, before it is used in the clinic.
Funded by the Stuart Scott Memorial Cancer Research Fund
The most common cause of cancer-related sickness and death is cancer spread throughout the body. Cells become cancer when they have too many changes. In order to stop the effects of these changes, we need to know more about what causes them. My lab is characterizing the cell changes that effect cancer spread in lung and head and neck cancer. This work will help identify the specific changes that could be targeted in new treatments to improve patient well-being and survival.
The most common mutation found in patients with pancreatic cancer is a mutation in the Kras gene. However, this mutation is not sufficient for initiation and progression of pancreatic cancer. It is well known that inflammation is a risk factor for pancreatic cancer and can accelerate pancreatic cancer development. We have shown that during pancreatic inflammation, caused by cigarette smoking, stones, or other stressors, immune cells secreting a factor named IL-17 are recruited to the pancreas and are capable of inducing pancreatic cancer initiation and development. We are now interested in understanding the role of these cells in regulating pancreatic cancer stem cells induction and invasiveness. This information will be useful for pancreatic cancer prevention and treatment given the existence of commercially available monoclonal antibodies that target specifically these cells.
Funded by the Stuart Scott Memorial Cancer Research Fund
Multiple myeloma is an incurable cancer of plasma cells. There is no cure for multiple myeloma yet. The T cells of the immune system can protect us in the long term from infections and from cancer. Here, we propose to engineer human T cells so they can recognize and kill myeloma tumor cells. This project will test several ways of engineering the T cells to make them as safe as possible and as effective as possible. Our goal is to use this information to treat human patients with multiple myeloma.
Funded by the Dick Vitale Gala in Memory of John Saunders
Our goal is to understand why infants get a type of cancer called leukemia. Infant leukemia is devastating, and most of these children will die of their cancer. A common question parents ask is, “Why did my child get this disease?” Our work suggests that the cause is, at least partly, genetic. My lab is developing tools to determine which genetic changes are actually important for causing infant leukemia and which are not. We are focusing on changes that are inherited from generation to generation, even in families that have no history of infant leukemia. Through our studies, we hope to answer the “Why?” question for parents and other relatives, and we hope develop new treatments for infant leukemia that are more effective and less toxic.
Pancreatic cancer is a very aggressive disease. The 5-year survival rate is a shockingly low 8%. This statistic has hardly changed in 30 years. This is because effective treatment options for pancreatic cancer do not exist.
A notable feature of pancreatic tumors is a scar-like barrier that protects the cells from anti-cancer drugs. This barrier also restricts oxygen and nutrient access, placing the cancer cells on the brink of starvation. The Lyssiotis lab seeks to figure out how these cancer cells survive and grow with limited nutrient access.
Pancreatic tumors are also known to be made up primarily of non-cancer support cells. My lab recently found that these non-cancer cells provide the cancer cells with nutrients. In this proposal, my laboratory will determine the role of these nutrients on tumor growth. A means to block this pathway would starve the already nutrient deprived cancer cells. This will provide important insights to design new therapies for this dreadful disease.
More than 40,000 American women die of breast cancer each year. One out of every eight women in the U.S. will develop invasive breast cancer during their lifetime. In 70% of these women, estrogen and estrogen receptor α (ERα) are key players in breast cancer diseases. Keeping this endocrine signaling function low by endocrine therapy is the best treatment right now. Yet, after 5 years, hormonal treatment stops working in more than 30% of these patients and the disease returns. Because hormone resistance is still a challenge, there are few effective therapies for these patients. We plan to study estrogen and ERα related to hormone resistance.
ERα binds DNA elements that regulate gene expression. These elements are very important in cancer development and progression. When these elements lose control, breast cancer becomes resistant to hormones. Thus, if we can find ways to understand and correct these elements in hormone resistant cells, we can find cures for ERα-positive breast cancers. The goal of this project is to understand how ERα controls DNA elements. We will identify markers to measure the presence and progression of breast cancer. Our research results may lead to new therapies that target this disease. Discoveries from this project may help with treating other cancers and may be useful for other research fields.
