Areas of Research
- DNA Repair
- B Cell Biology
- Host-Pathogen Interactions
- Tumor Microenvironment
Research in the McBride Lab focuses on B cell function and immunoglobulin repertoire. Laboratory research encompasses mechanisms of antibody diversification, host-pathogen interactions between B cells and gammaherpesviruses, and the role of B cells in immunotherapy response. High-throughput, single-cell immunoglobulin cloning and antibody characterization is a major pipeline in the lab.
The McBride lab is making fundamental discoveries addressing the biology of B lymphocytes, specialized white blood cells that can differentiate into antibody-producing plasma cells. B cells are critical players in the humoral component of the adaptive immune response. During immune responses, mature B cells diversify immunoglobulin (Ig) genes through somatic hypermutation (SHM) and class-switch DNA recombination (CSR). SHM alters antibody affinity by introducing nucleotide changes in the part of the Ig genes encoding the antigen-binding, variable region of antibodies. B cells that make antibodies with improved antigen affinity are positively selected during the process of affinity maturation. CSR is a region-specific recombination reaction that replaces one antibody-constant region with another, thereby altering antibody effector function while leaving the Ig variable region and its antigen binding specificity intact. These mechanisms lead to the creation of a variety of Ig molecules in an individual, the sum total of which make up the immunoglobulin repertoire for that individual.
Ongoing laboratory research projects are defining the biology of B cells, particularly the molecular processes required for normal antibody immunoglobulin diversification; how B cells in the tumor microenvironment and the immunoglobulin repertoire contribute to immunotherapy response; and how subversion of the immune repertoire can lead to pathogenesis. The laboratory is highly vested in their novel, high-throughput pipeline for defining the immunoglobulin repertoire and for rapidly and inexpensively creating custom, sequence-defined, recombinant antibodies.
In an exciting new advancement with the potential to translate basic research findings into clinical advancements, MD Anderson has partnered with Panacea Venture to launch Manaolana Oncology (mana'olana means “hope” in Hawaiian). The new company will develop recombinant monoclonal antibody-based therapies that target cell-surface antigens on cancer cells, using novel methods developed in the McBride lab. These antibodies will be clinically evaluated as cancer treatments.