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. 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.
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.
Saribasak H, Maul RW, Cao Z, Yang WW, Schenten D, Kracker S, Gearhart PJ. DNA polymerase ζ generates tandem mutations in immunoglobulin variable regions. J Exp Med. 2012;209(6):1075-81.
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.
Maul RW, Gearhart PJ. AID and somatic hypermutation. Adv Immunol. 2010;105:159-91.
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.
Zanotti KJ, Maul RW, Castiblanco DP, Yang W, Choi YJ, Fox JT, Myung K, Saribasak H, Gearhart PJ. ATAD5 deficiency decreases B cell division and Igh recombination. J Immunol. 2015;194(1):35-42.