Patricia J. Gearhart, Ph.D.

Senior Investigator

Laboratory of Molecular Biology and Immunology

NIA

251 Bayview Boulevard
Suite 100
Baltimore, MD 21224

410-558-8561

gearhartp@mail.nih.gov

Research Topics

AID and Somatic Hypermutation: Somatic hypermutation of immunoglobulin genes occurs at a frequency that is a million times greater than mutation in other genes. Mutations are found in both variable genes and switch regions before constant genes. We have used biochemical and genetic techniques to study this fascinating process that occurs constantly in every B lymphocyte in the human body. Hypermutation is initiated when the activation-induced deaminase (AID) protein deaminates cytosine in DNA to uracil.

Biography

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.

Selected Publications

  1. Maul RW, Chon H, Sakhuja K, Cerritelli SM, Gugliotti LA, Gearhart PJ, Crouch RJ. R-Loop Depletion by Over-expressed RNase H1 in Mouse B Cells Increases Activation-Induced Deaminase Access to the Transcribed Strand without Altering Frequency of Isotype Switching. J Mol Biol. 2017.

  2. Maul RW, Saribasak H, Martomo SA, McClure RL, Yang W, Vaisman A, Gramlich HS, Schatz DG, Woodgate R, Wilson DM 3rd, Gearhart PJ. Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nat Immunol. 2011;12(1):70-6.

  3. 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 V<sub>H</sub> and Vκ Genes with Somatic Hypermutation. J Immunol. 2017;198(5):1921-1927.

  4. Maul RW, Cao Z, Venkataraman L, Giorgetti CA, Press JL, Denizot Y, Du H, Sen R, Gearhart PJ. Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo-activated cells. J Exp Med. 2014;211(11):2297-306.

  5. 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.


This page was last updated on August 7th, 2017