Grant Archive - Page 29 of 141

Jasmine Zhou, PhD

Lung cancer is the leading cancer killer in both men and women in the U.S. Early detection is the most effective way to fight against this deadly disease. In recent years, an imaging method known as low-dose CT (LDCT) scan has been studied in people at higher risk of getting lung cancer. LDCT scans can help find nodules in the lungs that may be cancer. However, majority of those nodules are actually benign, yet exposing many of those patients to a needle biopsy or other invasive procedures. Hence, there is an urgent and unmet need for an accurate and non-invasive approach to distinguish those nodules that are malignant from those that are not. In this proposal, we will develop and validate a novel method to integrate a blood test and the LDCT imaging for the early detection of lung cancer. Specifically, from blood we extract cell-free DNA, from which we develop an ultra-sensitive assay to profiles the epigenome of cell-free DNA, therefore to detect even a trace amount of tumor DNA. Using advanced machine learning algorithms on the integrated genomics and imaging data, we aim to significantly improve the accuracy of the cancer detection. For those patients with nodules identified from LDCT, we will integrate the two sources of information to determine whether the nodules are malignant or benign.

Beau Webber, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Osteosarcoma (OSA) is a bone cancer that mostly affects young people. Surgery and chemotherapy are the most common forms of treatment but can cause serious side-effects that make patients very ill. When a patient’s OSA has spread from the bone to the lungs it is much harder to treat. Recent research has shown that immune cells can be engineered to improve their ability to fight cancer. This approach has cured patients with certain blood cancers when all other previous therapies failed. However, this approach is less effective in “solid” cancers like OSA. We are pursuing a new approach where immune cells that naturally recognize mutated proteins in a patient’s tumor (TIL) are collected and grown to large numbers before returning them to the patient. This approach has achieved cures in several solid cancers, including those that have spread to other areas of the body including the lungs, but it is not always effective. In previous work, we found that disabling a gene called CISH allows TIL to kill cancer cells more effectively. We are currently testing this in a clinical trial in patients with gastrointestinal cancer. In the current proposal, our goal is to see if this approach can also be used to treat OSA. If successful, our approach may offer a curative option with far fewer side-effects compared to current therapies.

Pavlos Msaouel, MD, PhD

Renal medullary carcinoma (RMC) is a rare but deadly kidney cancer that mainly occurs in young individuals of African descent that carry a blood disorder called sickle cell trait. Most people carrying the sickle cell trait never develop any symptoms. Many do not even know that they have it. Approximately 1 in 14 African Americans have the sickle cell trait and are at risk for developing RMC at an average age of 28 years old. RMC is also an under-recognized global health challenge because the sickle cell trait is found in ~300 million individuals around the world, mainly in Africa. Almost every patient with RMC is diagnosed late, when the cancer has already spread to other organs. Less than 5% of these patients survive beyond 3 years. Furthermore, many patients with RMC are initially misdiagnosed and lose precious time while being treated with the wrong therapies. The chances of a cure considerably increase when RMC is diagnosed and treated early. With the help of our patient advocates, we have established the largest collection of blood and tissue samples from patients with RMC worldwide. Using these samples, we have found evidence that patients with RMC have antibodies against unique proteins found only in cancer. We have developed a novel technology that allows the detection of more than 400,000 of these antibodies using only a drop of blood, quickly (within 3 days) and affordably. Our proposal aims to investigate and develop this new approach for the early diagnosis of RMC.

Douglas Grossman, MD, PhD

Nick Valvano Translational Research Grant*

Basal (BCC) and squamous cell (SCC) carcinomas are the most common form of skin cancer. If diagnosis is delayed, the tumors may require surgery that is more extensive. These tumors may be superficial, which are slow-growing, confined to the outer skin layers, and can usually be treated without surgery. Alternatively, they may be invasive, penetrating the deeper skin layers to destroy these tissues, often requiring surgery that can be costly and painful. While these skin cancers often may be diagnosed with the naked eye, it is difficult to tell whether they are superficial or invasive. Thus, there is a clear need for a new diagnostic approach that can inform patients and their physicians whether a particular lesion should be biopsied, and whether evaluation is urgent if the lesion is likely to be invasive. Currently there is no non-invasive (without biopsy) to accomplish this. Here, we propose to develop a new test based on micro-RNAs (miRNAs) that can be recovered simply on adhesive tape from suspicious skin lesions. We believe these miRNAs can be used to identify non-melanoma skin cancers and their subtypes as a new non-invasive way to decide whether (and how urgent) a biopsy needs to be performed. First, we will determine which miRNAs are most associated with superficial and invasive skin cancers by analyzing miRNAs in previously biopsied tissues. Second, we will validate this technique on a group of patients who come to clinic with a suspicious skin lesion.

Claude Sirlin, MD

Liver cancer is one of the deadliest cancers in the world and it is becoming more common in the United States due to liver disease or liver scarring. Patients with liver problems are at risk of developing liver cancer, and if the cancer is found at an early stage, it can be cured. Therefore, patients with liver problems should be screened regularly so that the cancer can be found early. Unfortunately, current screening techniques are not very sensitive and require trips to special imaging centers twice a year. Our work will create a new and better screening tool for early detection of liver cancer that can be used anywhere. By improving the quality and access to better imaging, screening will be more effective and can be done wherever patients need it most, without the need to travel to a hospital or specialized imaging center. We believe that by improving both the quality and access to screening, patients with liver cancer will be found at an earlier stage, allowing for better patient care. Further, easier access to this new screening tool will allow more people to access the healthcare they need.

Pratiti Bandopadhayay, MBBS, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Brain tumors are the leading cause of cancer related deaths and long term side effects in children. Treatments that are specifically directed to tumors, while sparing normal brain cells, are desperately required to increase the effectiveness of treatments and to reduce side effects. This project is focused on trying to find ways to inhibit specific mutations in a group of genes that are found across common childhood gliomas. Our hope is that our work will help us find ways to use medications that target these mutations specifically to allow precision medicine approaches.

Vida Henderson, PhD, PharmD

Funded in collaboration with ESPN

Research studies that test how new cancer drugs work often don’t include all members of the United States population. Scientists are unable to tell how well these new treatments work in diverse groups. Our team will study how Black cancer patients and their families decide whether participating in a research study is right for them. We will talk with Black cancer patients and their families, doctors, cancer support groups, and Black community members to help us develop a public service video about clinical trials. We will also develop a plan to share information about clinical trials among Black communities. This approach will help us develop a public service video that is based on the needs, experiences, and strengths of Black communities that can be shared widely.

Jason Schwartz, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

The Schwartz Lab studies two genes, SAMD9 and SAMD9L that are known to cause a bone marrow failure syndrome in children called myelodysplastic syndrome (MDS). There are no reliable pediatric MDS model systems, thus we have created one from a special type of stem cell that contains mutated SAMD9 or SAMD9L. It is important to have these new cell lines, because cells that we can obtain from patients do not grow well or for a long time making studying them very hard. We will perform several tests in our new model system to determine why mutations in SAMD9 and SAMD9L cause blood stem cells to die. Together with our cell lines we have also developed a second set of tools that will allow us to turn on or to turn off SAMD9 or SAMD9L without using interferon—an inflammatory substance in the cell that turns on many other cell processes including SAMD9 and SAMD9L. We have completed initial experiments that suggest that SAMD9 and SAMD9L are important in how cells communicate during inflammation and other immune responses. Our proposed experiments will further determine how disease-causing mutations in SAMD9 and SAMD9L disrupt communication in these important cellular pathways. Understanding how SAMD9/9L mutations effect the blood stem cells will help us determine the right treatment approach for patients with pediatric MDS, because some patients with SAMD9 or SAMD9L mutations may not need treatment at all.

Grant Rowe, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund and the V Foundation Wine Celebration in honor of Bob McClenahan

Leukemia is a blood cancer that can be fully treated with anti-cancer drugs in most people. However, many people with leukemia do not respond to these drugs and are at risk of dying. It is not known why some leukemias respond to treatment while others do not. We believe that the type of normal blood cell that becomes leukemic impacts the behavior of individual leukemias. We believe that if a normal blood cell possessing the ability to form many other types of blood cells (in other words, it is a blood ‘stem cell’) turns into leukemia, this leukemia will be hard to treat. On the other hand, if the normal blood cell does not possess such properties – it is a more mature blood cell – this leads to treatable leukemia. In this proposal, we will apply our experience in engineering different types of blood cells (stem cells and more mature blood cells) to become leukemic. We will ask how the type of healthy blood cell impacts the behavior of the resulting leukemia. We will use genetics to understand how the properties of normal blood stem cells are transferred to leukemia cells to impact aggressiveness. We expect that successful completion of this study will improve our understanding as to why some forms of leukemia are treatable and why some are not treatable. We hope that these conclusions can lead to better understanding of individual patient leukemias and improved treatments.

Chrysothemis Brown, MD, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund with support from the Rudd Foundation in memory of Leslie Rudd

Immunotherapy is a type of cancer treatment that boosts the body’s immune system so that it can fight the cancer. Whilst this type of treatment has proven very successful for certain cancers in adult patients, this approach has been much less effective for the treatment of cancer in children. One reason for this is that the immune system of children is very different from adults and may not respond to treatments designed to target adult immune cells. Remarkably little is known about the cell types in children that suppress anti-cancer immune responses. The Brown Lab recently discovered a new type of immune cell —Thetis cells — that may be pivotal in reducing the efficacy of immunotherapy in the very young. We hypothesize that Thetis cells help to “train” T cells not to attack the body’s own normal cells, and in so doing creates an immune environment that also tolerates malignant tumors. In this project, the Brown Lab seeks to reveal, on the molecular level, how Thetis cells work and thus how to create immune therapies for children while not provoking auto-immune diseases that overactive T cells sometimes cause.