The initial treatment of men with prostate cancer is highly successful in stopping the primary cancer. However, years later men often develop cancer again and it is commonly deadly. One explanation for cancer returning is that the cancer was sleeping and in doing so, it was not affected by the first medicine. Our team discovered a new treatment to put cancer to sleep in the body. By using laboratory tests and information from patients, we discovered a “fingerprint” that can tell us if and how the cancer is sleeping or growing. However, for reasons that remain unclear, the sleeping cancer eventually awakens in a deadly form. We discovered that using known medicines we could keep the cancer asleep. We propose to use these medicines that are available for other diseases to induce an constant sleeping state in cancer, preventing its awakening. We will also find new indicators of the sleeping or growing state of cancer using a blood test. If successful, our new treatment to keep cancer sleeping may provide a new cure for men with prostate cancer.
A set of proteins are highly active in cancer. They can add small groups to a series of target proteins. These uncommon additions are often linked with tumors found in breast, liver, and other tissues. To date, it is still unclear how those aberrant proteins cause cancer. To answer this question, it is crucial to know all the targets that they act on in live cancer cells. But no method has been made available to resolve this key issue. In this project we are aimed to create an innovative platform to achieve this goal. Our research plan will use chemistry and biotechnology to make new tools for target identification. A particular member in this group will be chosen for this work. Because it shows much higher activities in diverse types of cancer. The full range of targets for this protein in live cancer cells will be clearly assigned for each specific type of cells. Moreover, the patterns, levels, and time courses of such additions in live cells can be directly viewed and precisely measured by our creative approach. These findings will lead to unveil the interaction networks of this cancerous protein to guide our further studies. The fundamental knowledge obtained from this work will advance our understanding of cancer. Importantly, it will foster the development of new approaches for cancer detection and treatment.
Prostate cancer is the second most frequently diagnosed cancer worldwide. In the US, more than 230,000 cases are diagnosed yearly, affecting 1 in 7 men. If detected early, the cure rate for these cancers is high – nearly all patients will be disease-free after five years. However, in patients whose cancers either re-appear after treatment or spread to other organs, therapies are limited mainly to symptomatic relief. Patients diagnosed at this stage usually live no longer than 20 months. Therefore, a major challenge in treating advanced prostate cancer is that the standard therapies, including radiation and medicine, are not effective in killing these cancer cells.
A small proportion of tumor cells, known as cancer stem cells (CSCs), is particularly important in promoting cancer, because they 1) can give rise to an entire tumor from a single cell, and 2) are more resistant to treatment than other tumor cells. Efforts to identify and then kill CSCs hold the key to effective prostate cancer treatment. The goal of our work is to define the molecular mechanisms that drive growth of prostate cancer CSCs. Once identified, those factors could serve as “biomarkers” or diagnostics. In addition, drugs could be designed to target those factors as a way of blocking tumor growth.
Skin melanoma is one of the fastest rising cancers. It is also the deadliest form of skin cancer. Sun and UV exposure are major risk factors for the development of melanoma. This is due to the fact that UV rays can change the DNA of normal cells. These DNA changes, called mutations, can turn a normal cell into a cancer cell. My research focuses on identifying UV-induced mutations in melanoma. In this proposal, I will test which of these mutations cause melanoma using a new research tool. I will determine which mutations affect the response to melanoma therapies used in the clinic. My work may help explain why some patients respond to certain treatments and others do not. This is information is important to know. It will allow doctors to prescribe drugs that are most likely to work for a specific patient. Ultimately, I will use findings from this proposal to develop new therapeutic strategies to treat melanoma.
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.
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.
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