DESCRIPTION (provided by applicant): The Byrd translational laboratory research program focuses on basic and translational biologic questions to develop novel immunologic and targeted therapies for hematologic malignancies. Chronic lymphocytic leukemia (CLL) is utilized as our disease model as it allows integration of mechanistic and genetic studies in spontaneous leukemia mouse models with studies using primary tumor samples, thereby enhancing the clinical relevance of our findings. Our highly collaborative laboratory team works to identify, dissect, and solve challenges in leukemia therapeutic development that capitalizes on the strengths of each to drive projects to clinical application. It also allows us to exploit diverse techniques (e.g. proteomics, next-generation sequencing) and embark on new areas (e.g. novel drug delivery methods, target identification, introduction of new animal models) to translate our findings across multiple human diseases. This strategy has resulted in powerful collaborations, recruiting skilled researchers from other fields to apply their knowledge to leukemia. I envision the greatest impact from my research will come from integrating therapeutics that target tumor survival pathways with agents that reverse immune tolerance to facilitate long-term remissions or cure. My work to date has resulted in the approval of two agents for CLL therapy that prolong survival. Our ongoing work with imbrutinib dispels a commonly held paradigm that it is not possible to develop a general "disease-targeted therapy" when a specific genetic aberration is not present. My hypothesis is that general disease-targeted therapy requires dual tumor-targeted and immunologic modulation. I seek to aggressively develop this concept and extend it to other areas as our data directs us.