Areas of Research
- DNA Repair Research
- Epigenetics Research
Research in the McBride Lab focuses on B cell function and antibody 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 antibody cloning and characterization is a major pipeline in the lab.
DNA damage and mutation of the genome are the basis of carcinogenesis and these processes are generally thought of as activities a cell should avoid at all costs. However, there are instances of DNA damage having beneficial effects. For example, mammals have evolved programmed DNA damage as a means to diversify the immune repertoire, protect against viral infection, and instigate epigenetic reprogramming.
The McBride laboratory is interested in the enzyme activation-induced deaminase (AID), which causes programmed DNA damage in germinal center B cells through the process of somatic hypermutation. AID-induced DNA damage is essential for repertoire diversity, but it may also cause collateral damage that can lead to carcinogenesis. They are seeking to understand the mechanisms that control AID activity and contribute to its proper function in immunity and epigenetic reprogramming as well as its rogue activity that can cause cancer.
Somatic hypermutation has been difficult to study, hampered by the heterogeneity of mutation, rarity of events, and difficulty in measuring mutation rates and target genes. However, the McBride lab has overcome these difficulties by using a novel cutting-edge technique that allows single-cell mutation analysis to investigate the genetic, environmental, and cell signaling pathways that underlie nucleic acid mutation.
The lab is also defining the role of uracil DNA glycosylases in gammaherpesvirus pathogenesis and B cell development. Gammaherpesviruses, such as Epstein-Barr virus and Kaposi sarcoma herpesvirus, establish life-long latent infections that have been linked to the development of lymphomas and other cancers. They discovered that viral uracil DNA glycosylase alters somatic hypermutation and by using single-cell and germinal center cell population analysis, they found that gammaherpesvirus-infected germinal center cells express a distinct and abnormal immunoglobulin repertoire.