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.
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.
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.
Support for the Liposarcoma Genome Project was funded by
Alex Gould and Friends in memory of Kathryn Gould.
Liposarcoma Genome Project – Liposarcoma is the most common type of cancer that arises in soft tissue. These tumors often present as low grade tumors initially, but a subset of patients will experience recurrence of a higher grade tumor. Those patients who recur with higher grade tumors do poorly. Therefore, our research focuses on understanding these high grade tumors. We will explore the genetic changes between the low grade and high grade tumors in order to understand the molecular features that underlie high grade transformation. We will begin by sequencing gene mutations in these tumors and surveying gene activity in each tumor type (Aim 1). Mechanisms that govern which genes are on and off frequently involve how the DNA is packaged and structurally arranged in the cell. Therefore, we will characterize the packaging (chromatin) and structure (topology) of the genomic DNA in these tumors (Aim 2). By elucidating mechanisms by which tumor cells alter gene expression, we will better understand the genes and pathways that sustain them. Finally, we will develop models of these tumors (Aim 3). We can use these models to test driver genes and candidate therapeutic targets identified in our study. We believe that our interdisciplinary team of clinicians and scientists is poised to complete the proposed aims, which should yield important insights into liposarcoma biology and guide future clinical strategies.
