Deciphering the Context-Dependent Role of Spliceosomal Mutations in Myeloid Blood Cancers
Abstract
As a molecular biologist with a Bachelor, Master, and PhD in the field of Biomedical Sciences, my studies have always focused on clinically relevant research questions. I chose to do my first research internship during my masters on blood cancer. This turned out to be an excellent choice, because I absolutely loved the complexity of the blood system, and there is a big unmet need to improve blood cancer therapies. After successfully completing my PhD on blood cancer and bleeding disorders (six major publications) and starting my post-doctoral fellowship (one major blood cancer publication so far), I now want to dive deeper into blood cancers by studying a key biological process called “RNA splicing.” This award and my research development plan will allow me to excel in the blood cancer and RNA splicing field by interacting with the leading experts in this field (Dr. Graubert and Dr. Abdel-Wahab) and acquiring knowledge on state-of-the-art techniques such as single cell RNA-sequencing (Dr. Van Galen). Additionally, it will allow me to acquire bio-informatic analysis and coding skills (Harvard Chan Bioinformatics Core and Abdel-Wahab laboratory), which I believe are indispensable skills for my future career. Lastly, I will be able to develop research lines that are distinct from my mentor (Dr. Mullally) and help me prepare to start my own independent lab focused on RNA splicing in blood cancers. This project will significantly contribute to our knowledge on how blood cancers develop, identify drug targets, and validate several potential drug targets that I have already identified. These are the first steps in the development of new cancer drugs, after which an existing drug or a new drug can be identified for further preclinical investigations in animal models and future testing in clinical trials. In this process, I will try to repurpose an existing drug, which is much quicker than developing a new drug. Even though my research describes the first steps in drug development, I have very unique and focused research aims that are likely to benefit not only blood cancer patients with defective RNA splicing factors, but also patients with other cancers. The blood cancer I study is called Myeloproliferative Neoplasms (MPN), in particular a group of patients with an aggressive MPN type called, myelofibrosis. In addition to a median survival of only 3 years for the majority of patients with myelofibrosis, this is a disease characterized by substantial morbidity and therefore quality of life is typically poor during these years. On top of that, patients with myelofibrosis are at high risk of developing acute myeloid leukemia (AML), which is generally not responsive to chemotherapy. The only curative treatment option is a risky and complicated hematopoietic stem cell transplantation. Although current therapies reduce MPN symptoms, they are not disease modifying. Therefore, there is high unmet need for drugs that can kill MPN cancer cells and prolong survival of these patients. Cancer research and new medications benefit military personnel, because Service members are highly exposed to cancer-inducing chemicals. Additionally, many cancers occur more frequently in elderly patients and the proportion of elderly and affected Veterans is likely significant due to aging of the population. MPN specifically is a disease of the elderly and therefore, this research proposal is of high relevance to the military. Besides blood cancers, defective RNA splicing occurs in several cancer types and will hence benefit military cancer patients more broadly. Because of the high toll of cancer on Veterans, active military and their beneficiaries and the broad applicability of the knowledge obtained through this research, Service members will maximally benefit from the outcomes of this important investigation. Through the proposed work, I expect to bring innovative approaches to the treatment of MPN blood cancers that will at minimum improve the qu
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010904
Entities
People
- Anna E Marneth
Organizations
- United States Army