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.
Chronic lymphocytic leukemia is the most common type of adult leukemia. This proposal seeks to integrate targeted therapy with immune therapy to produce impactful curative therapies for patients with this disease. The knowledge derived from these investigations will be then be extended to other types of blood cancers.
|O'Brien, Susan; Furman, Richard R; Coutre, Steven et al. (2018) Single-agent ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience. Blood 131:1910-1919|
|O'Brien, Susan M; Jaglowski, Samantha; Byrd, John C et al. (2018) Prognostic Factors for Complete Response to Ibrutinib in Patients With Chronic Lymphocytic Leukemia: A Pooled Analysis of 2 Clinical Trials. JAMA Oncol 4:712-716|
|Byrd, John C; Smith, Stephen; Wagner-Johnston, Nina et al. (2018) First-in-human phase 1 study of the BTK inhibitor GDC-0853 in relapsed or refractory B-cell NHL and CLL. Oncotarget 9:13023-13035|
|Woyach, Jennifer A; Ruppert, Amy S; Heerema, Nyla A et al. (2018) Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. N Engl J Med 379:2517-2528|
|Reiff, Sean D; Muhowski, Elizabeth M; Guinn, Daphne et al. (2018) Noncovalent inhibition of C481S Bruton tyrosine kinase by GDC-0853: a new treatment strategy for ibrutinib-resistant CLL. Blood 132:1039-1049|
|Rosko, Ashley E; Huang, Ying; Benson, Don M et al. (2018) Use of a comprehensive frailty assessment to predict morbidity in patients with multiple myeloma undergoing transplant. J Geriatr Oncol :|
|Rogers, Kerry A; Huang, Ying; Ruppert, Amy S et al. (2018) Phase 1b study of obinutuzumab, ibrutinib, and venetoclax in relapsed and refractory chronic lymphocytic leukemia. Blood 132:1568-1572|
|Byrd, John C; Ruppert, Amy S; Heerema, Nyla A et al. (2018) Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy: results for CALGB 10404 (Alliance). Blood Adv 2:1705-1718|
|Ozer, Hatice Gulcin; El-Gamal, Dalia; Powell, Ben et al. (2018) BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor. Cancer Discov 8:458-477|
|Reiff, Sean D; Mantel, Rose; Smith, Lisa L et al. (2018) The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation. Cancer Discov 8:1300-1315|
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