Distinguished Professor, Department of Cell Biology
Distinguished Professor, Department of Medicine (Infectious Diseases)
Faculty Supervisor, Hybridoma and Tissue Culture Facility
The Harry Eagle Chair in Cancer Research/National Women's Division
Our laboratory is studying how antibody forming cells respond to antigen by producing antibodies that have undergone somatic mutation and class and subclass switching so that they can produce higher affinity antibodies with more useful effector functions.
The molecular and biochemical mechanisms of antibody V region hypermutation and class switch recombination is being studied in mice that are genetically defective in various repair proteins and in vitro in human Burkitt’s lymphoma cells which are either undergoing V region mutation constitutively or can be induced to mutate by crosslinking their surface Ig and co-cultivation with T cells.
These cell lines and genetically defective mice are being used to study the role of activation induced deaminase, mismatch repair and of error prone polymerases in the hypermutation and isotype switching processes that can also lead to the malignant transformation of B cells. Chromatin immunoprecipitation, DNA arrays and transfected Ig genes are being used to identify cis-acting DNA sequences and additional transacting proteins that target mutation and switching to Ig genes.
In a second project, we are studying the role of mutation and isotype switching in generating antibodies that protect mice from lethal toxins. Momoclonal antibodies to such toxins are generated and the impact of affinity and isotype are determined in vitro and in vivo.
1. Induction of somatic hypermutation is associated with modifications in immunoglobulin variable region chromatin. Caroline J. Woo, Alberto Martin, and Matthew D. Scharff Immunity 19:479-489, 2003
2. Msh2 ATPase Activity is Essential for Somatic Hypermutation at A-T Basepairs and for Efficient Class Switch Recombination Alberto Martin, Ziqiang Li, Diana Lin, Philip D. Bardwell, Maria D. Iglesias-Ussel Winfried Edelmann, and Matthew D. Scharff. J.Exp.Med. 198:1171-1178, 2003
3. Mutations in AID and UNG extend the function of AID. Ziqiang Li, Caroline Woo and Matthew D. Scharff. News and Views Nat Immunol.
4: 945-946, 2003 4. Antibodies to KLH cross-react with an epitope on the polysaccharide capsule of Cryptococcus neoformans and other carbohydrates: implications for vaccine development Rena J. May, David O. Beenhouwer, Matthew D. Scharff, J. Immunol 171:4905-4912, 2003
5. Altered somatic hypermutation and reduced class switch recombination in Exonuclease 1-mutant mice. Philip D Bardwell, Caroline J Woo, Kaichun Wei, Ziqiang Li, Alberto Martin, Stephen Z Sack, Tchaiko Parris, Winfried Edelmann, and Matthew D Scharff Nat. Immunol. 5: 224-229, 2004
6. The generation of antibody diversity through somatic hypermutation and class switch recombination. Li, Z. Woo, C. J. Iglesias-Ussel, M.D., Ronai, D., Scharff, M. D. Genes and Development, 18:1-11, 2004
7. Molecular Mechanisms of Hypermutation. Nancy Maizels & Matthew D. Scharff in Molecular Biology of B cells. (eds T. Honjo, F. W. Alt & M.S. Neuberger) Elsevier Acamdemic Press, 2004
8. Examination of Msh6- and Msh3-deficient Mice in Class Switching Reveals Overlapping and Distinct Roles of MutS Homologues in Antibody Diversification. Li Z, Scherer SJ, Ronai D, Iglesias-Ussel MD, Peled JU, Bardwell PD, Zhuang M, Lee K, Martin A, Edelmann W, Scharff MD. J Exp Med. 200, 47-59, 2004.
9. Differential regulation of histone acetylation and generation of mutations in switch regions is associated with Ig class switching Li, Z, Luo, Z and Scharff, M.D. Proc Natl Acad Sci U S A.101:15428-33. 2004.
10. The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies. Luo, Z, Ronai, D, and Scharff, M.D. J Allergy Clin Immunol. 114:726-35; 2004
More Information About Dr. Matthew Scharff
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Chanin Building, Room 403
Bronx, NY 10461