Patricia J. Gearhart, Ph.D.
Laboratory of Molecular Biology and Immunology
251 Bayview Boulevard
Baltimore, MD 21224
AID and Somatic Hypermutation:
Somatic hypermutation of immunoglobulin genes occurs at a frequency that is a million times greater than mutation in other genes. We have used biochemical and genetic techniques to study this fascinating process that occurs in B lymphocytes. Mutations are found in variable genes to produce high affinity antibodies, and in switch regions before constant genes to change heavy chain classes. Hypermutation is initiated when the activation-induced deaminase (AID) protein deaminates cytosine in DNA to uracil. During repair of uracils, low-fidelity DNA polymerases introduce nucleotide substitutions. We are studying the role of transcription in targeting this dangerous mutagen to the immunoglobulin loci.
Changes in B Cells during Aging:
B cells from old mice are hyper-responsive to antigen stimulation compared to their young counterparts. We are examining molecular changes in signaling pathways that arise in old cells during life-time exposure to endogenous antigens.
B Cells in Atherosclerosis:
Using mouse models, we demonstrated that antibodies to oxidized low density lipoproteins prevent disease, and antibodies to self-proteins increase inflammation. We are exploring the potential of antibodies as vaccines and as biomarkers of human disease.
Dr. Patricia Gearhart received her Ph.D. in immunology from the University of Pennsylvania in 1974. She performed postdoctoral training at the Johns Hopkins University and was a staff associate at the Carnegie Institution of Washington until 1982. She then became a faculty member at the Johns Hopkins University until 1995, when she moved to the NIA.
Zanotti KJ, Maul RW, Yang W, Gearhart PJ. DNA Breaks in Ig V Regions Are Predominantly Single Stranded and Are Generated by UNG and MSH6 DNA Repair Pathways. J Immunol. 2019;202(5):1573-1581.
Pape KA, Maul RW, Dileepan T, Paustian AS, Gearhart PJ, Jenkins MK. Naive B Cells with High-Avidity Germline-Encoded Antigen Receptors Produce Persistent IgM+ and Transient IgG+ Memory B Cells. Immunity. 2018;48(6):1135-1143.e4.
Russell Knode LM, Naradikian MS, Myles A, Scholz JL, Hao Y, Liu D, Ford ML, Tobias JW, Cancro MP, Gearhart PJ. Age-Associated B Cells Express a Diverse Repertoire of VH and Vκ Genes with Somatic Hypermutation. J Immunol. 2017;198(5):1921-1927.
Castiblanco DP, Maul RW, Russell Knode LM, Gearhart PJ. Co-Stimulation of BCR and Toll-Like Receptor 7 Increases Somatic Hypermutation, Memory B Cell Formation, and Secondary Antibody Response to Protein Antigen. Front Immunol. 2017;8:1833.
Maul RW, MacCarthy T, Frank EG, Donigan KA, McLenigan MP, Yang W, Saribasak H, Huston DE, Lange SS, Woodgate R, Gearhart PJ. DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes. J Exp Med. 2016;213(9):1675-83.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on April 2nd, 2021