Patricia J. Gearhart, Ph.D.
Laboratory of Molecular Biology and Immunology
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.
- Hutchinson MA, Park HS, Zanotti KJ, Alvarez-Gonzalez J, Zhang J, Zhang L, Telljohann R, Wang M, Lakatta EG, Gearhart PJ, Maul RW. Auto-Antibody Production During Experimental Atherosclerosis in ApoE-/- Mice. Front Immunol. 2021;12:695220.
- Alvarez-Gonzalez J, Yasgar A, Maul RW, Rieffer AE, Crawford DJ, Salamango DJ, Dorjsuren D, Zakharov AV, Jansen DJ, Rai G, Marugan J, Simeonov A, Harris RS, Kohli RM, Gearhart PJ. Small Molecule Inhibitors of Activation-Induced Deaminase Decrease Class Switch Recombination in B Cells. ACS Pharmacol Transl Sci. 2021;4(3):1214-1226.
- Maul RW, Catalina MD, Kumar V, Bachali P, Grammer AC, Wang S, Yang W, Hasni S, Ettinger R, Lipsky PE, Gearhart PJ. Transcriptome and IgH Repertoire Analyses Show That CD11chi B Cells Are a Distinct Population With Similarity to B Cells Arising in Autoimmunity and Infection. Front Immunol. 2021;12:649458.
- 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.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on Saturday, August 21, 2021