Professor, Department of Cell Biology
Chanin Bldg., Room 403
718.430.3527
matthew.scharff@einsteinmed.org
Research Interest
Recent Publications
Biosketch
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1. Error-prone Candidates Vie for Somatic Mutation. Poltoratsky, V., Goodman, M.E., and Scharff, M.D., J. Exp. Med. 192: 27-30, 2000.
2. Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Alberto Martin, Philip D. Bardwell, Caroline J. Woo, Manxia Fan*, Marc J. Shulman, Matthew D. Scharff. Nature 415: 802, 2002.
3. 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.
4. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Ronda Bransteitter, Phuong Pham, Matthew D. Scharff and Myron F. Goodman. Proc. Natl. Acad. Sci. USA 100: 4102-4107, 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. 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. (PMCID: PMC524454).
7. Complex regulation of somatic hypermutation by cis-acting sequences in the endogenous IgH gene in hybridoma cells. D. Ronai, M.D. Iglesias-Ussel, M. Fan, M.J. Shulman, M.D. Scharff. Proc Natl Acad Sci U S A. 102:11829-11834, 2005. (PMCID: PMC1188009).
8. The mismatch repair protein Msh6 plays a role in the targeting of AID to the Ig locus in vivo. Z. Li, C. Zhao, Z. Polonskaya, M. Zhuang, G. Yang, M.D. Iglesias-Ussel, Z. Luo, W. Edelmann, and M.D. Scharff. Immunity 24:393-403, 2006.
9. Detection of Chromatin-Associated ssDNA in Regions Targeted for Somatic Hypermutation. Ronai, D., Iglesias-Ussel. M.D., Fan, M., Li, Z., Martin, A and M. D. Scharff.J. Exp. Med. 204:181-190, 2007. (PMCID: PMC2118410).
10. The Biochemistry of Somatic Hypermutation. Peled, J.U., F. L. M. D. Kuang, Iglesias-Ussel, S. Roa, S.L. Kalis, M.F. Goodman and M.D. Scharff. Annual Reviews of Immunology. 26:481-511, 2008.
11. Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression. Roa S, Avdievich E, Peled JU, Maccarthy T, Werling U, Kuang FL, Kan R, Zhao C, Bergman A, Cohen PE, Edelmann W, Scharff MD. Proc Natl Acad Sci U S A. 105:16248-53. 2008. (PMCID: PMC2571010)
12. SHMTool: A webserver for comparative analysis of somatic hypermutation datasets. Maccarthy T, Roa S, Scharff MD, Bergman A. DNA Repair (Amst). 8:137-41, 2009. (PMCID: PMC2659805)
13. H3 trimethyl K9 and H3 acetyl K9 chromatin modifications are associated with class switch recombination. Kuang FL, Luo Z, Scharff MD. Proc. Natl. Acad. Sci. USA 106:5288-93, 2008 (PMCID: PMC2654022)
14. V-region mutation in vitro, in vivo and in silico reveal the importance of the enzymatic properties ofAID and the sequence environment. Thomas MacCarthy, Susan Kalis, Sergio Roa, Phuong Pham, Myron F. Goodman, Matthew D. Scharff, and Aviv Bergman. Proc Natl Acad Sci USA 106:8629-34, 2009 (PMCID: PMC2682541).
15. Molecular characterization of hybridoma subclones spontaneously switching at high frequencies in vitro. Iglesias-Ussel MD, Zavadil J, Scharff MD. J Immunol Methods. 350:71-78, 2009. (PMCID: PMC2762006)
16. The RNF8/RNF168 ubiquitin ligase cascade facilitates class switch recombination.Ramachandran S, Chahwan R, Nepal RM, Frieder D, Panier S, Roa S, Zaheen A, Durocher D, Scharff MD, Martin A.Proc Natl Acad Sci U S A. 107:809-14. 2010 PMID: 20080757.
17. Requirement for cyclin D3 in germinal center formation and function. Peled, J.U., Yu, J.J., Venkatesh, J., Bi, E., Ding, B.B., Krupski-Downs, M., Shaknovich, R., Sicinski, P., Diamond, B., Scharff, M.D., Ye, B.H. Cell Research 6: 631-46. 2010 PMID: 20404856.
18. MSH2/MSH6 complex promotes error-free repair of AID-induced dU:G mispairs as well as error-prone hypermutation of A:T sites. Roa S, Li Z, Peled JU, Zhao C, Edelmann W, Scharff MD.PLoS One. 2010 Jun 17;5(6):e11182.PMID: 20567595.
19. PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance.van Oers JM, Roa S, Werling U, Liu Y, Genschel J, Hou H Jr, Sellers RS, Modrich P, Scharff MD, Edelmann W.Proc Natl Acad Sci U S A. 107:13384-9, 2010PMID: 20624957
20. Msh6 protects mature B cells from lymphoma by preserving genomic stability. Peled JU, Sellers RS, Iglesias-Ussel MD, Shin DM, Montagna C, Zhao C, Li Z, Edelmann W, Morse HC 3rd, Scharff MD. Am J Pathol.177(5):2597-608, 2010. Epub 2010 Oct 7. PMID: 20934970
21. A requirement for FcγR in antibody-mediated bacterial toxin neutralization.Abboud N, Chow SK, Saylor C, Janda A, Ravetch JV, Scharff MD, Casadevall A.J Exp Med. 207(11):2395-405, 2010. PMID: 20921285PMC2964574
22. Generation, characterization and epitope mapping of neutralizing and protective monoclonal antibodies against staphylococcal enterotoxin B induced lethal shock. Avanish K. Varshney, Xiaobo Wang, Emily Cook, Kaushik Dutta, Matthew D. Scharff, Michael J. Goger, and Bettina C. Fries. J. Biol. Chem. published January 13, 2011 [Epub ahead of print]PMID: 21233204 [PubMed - as supplied by publisher]
23. Recombinase-mediated cassette exchange as a novel method to study somatic hypermutation in ramos cells. Baughn LB, Kalis SL, MacCarthy T, Wei L, Fan M, Bergman A, Scharff MD. MBio. 2011 Oct 11;2(5). pii: e00186-11. doi: 10.1128/mBio.00186-11. Print 2011. PMID: 21990614
24. Intra-clonal complexity in chronic lymphocytic leukemia: fractions enriched in recently born/divided and older/quiescent cells.Calissano C, Damle RN, Marsilio S, Yan XJ, Yancopoulos S, Hayes G, Emson C, Murphy EJ, Hellerstein MK, Sison C, Kaufman MS, Kolitz JE, Allen SL, Rai KR, Ivanovic I, Dozmorov IM, Roa S, Scharff MD, Li W, Chiorazzi N.Mol Med. 2011 Sep 23. doi: 10.2119/molmed.2011.00360. [Epub ahead of print]PMID: 21968788 [PubMed - as supplied by publisher]
25. Mismatch-mediated error prone repair at the immunoglobulin genes. Chahwan R, Edelmann W, Scharff MD, Roa S.Biomed Pharmacother. 2011 Dec; 65(8):529-36.
26. The use of Bcl-2 over-expression to stabilize hybridomas specific to the HERG potassium channel. Sroubek J, Krishnan Y, Chinai J, Buhl S, Scharff MD, McDonald TV. J Immunol Methods. 2011 Nov 15. [Epub ahead of print]PMID: 22107967 [PubMed - as supplied by publisher]
27. The ATPase activity of MLH1 is required to orchestrate DNA double-strand breaks and end processing during class switch recombination. Chahwan R, van Oers JM, Avdievich E, Zhao C, Edelmann W, Scharff MD, Roa S. J Exp Med. 209:671-8, 2012
28. Germline deletion of Igh 3' regulatory region elements hs 5, 6, 7 (hs5-7) affects B cell-specific regulation, rearrangement, and insulation of the Igh locus.Volpi SA, Verma-Gaur J, Hassan R, Ju Z, Roa S, Chatterjee S, Werling U, Hou H Jr, Will B, Steidl U, Scharff M, Edelman W, Feeney AJ, Birshtein BK. J Immunol. 188(6):2556-66, 2012 PMC3430471
29. AIDing antibody diversity by error-prone mismatch repair. Chahwan R, Edelmann W, Scharff MD, Roa S.Semin Immunol. 2012 Aug;24(4):293-300. Epub 2012 Jun 14.PMID: 22703640 PMC3422444
30. IGHV unmutated and mutated chronic lymphocytic leukemia cells produce activation-induced deaminase protein with a full range of biologic functions. Patten PE, Chu CC, Albesiano E, Damle RN, Yan XJ, Kim D, Zhang L, Magli AR, Barrientos J, Kolitz JE, Allen SL, Rai KR, Roa S, Mongini PK, Maccarthy T, Scharff MD, Chiorazzi N. Blood. 2012 Oct 15. [Epub ahead of print] PMID: 23071276 PMC3520620
31. AID and Apobec3G haphazard deamination and mutational diversity. Jaszczur M, Bertram JG, Pham P, Scharff MD, Goodman MF. Cell Mol Life Sci. 2012 Nov 22. [Epub ahead of print] PMID: 23178850 PMCID: PMC3600397 [Available on 2014/9/1] [PubMed - as supplied by publisher]
32. Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes. Schaetzlein S, Chahwan R, Avdievich E, Roa S, Wei K, Eoff RL, Sellers RS, Clark AB, Kunkel TA, Scharff MD, Edelmann W. Proc Natl Acad Sci U S A. Jul 2;110(27):E2470-9. doi: 10.1073/pnas.1308512110. Epub 2013 Jun 10.PMID: 23754438 PMCID: PMC3704034
33. HHLA2 is a member of the B7 family and inhibits human CD4 and CD8 T-cell function. Zhao R, Chinai JM, Buhl S, Scandiuzzi L, Ray A, Jeon H, Ohaegbulam KC, Ghosh K, Zhao A, Scharff MD, Zang X. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9879-84. doi: 10.1073/pnas.1303524110. Epub 2013 May 28. PMID: 23716685 [PubMed - in process] PMC3683785
34. Staphylococcal Enterotoxin B-Specific Monoclonal Antibody 20B1 Successfully Treats Diverse Staphylococcus aureus Infections. Varshney AK, Wang X, Scharff MD, Macintyre J, Zollner RS, Kovalenko OV, Martinez LR, Byrne FR, Fries BC. J Infect Dis. 2013 Sep 6. [Epub ahead of print] PMID: 23922375 [PubMed - as supplied by publisher] PMCID: PMC3836467 [Available on 2014/12/15]
35. The MutSβ complex is a modulator of p53-driven tumorigenesis through its functions in both DNA double-strand break repair and mismatch repair. van Oers JM, Edwards Y, Chahwan R, Zhang W, Smith C, Pechuan X, Schaetzlein S, Jin B, Wang Y, Bergman A, Scharff MD, Edelmann W. Oncogene. 2013 Sep 9. doi: 10.1038/onc.2013.365. [Epub ahead of print] PMID: 24013230 PMCID: PMC3961563
36. A source of the single stranded DNA substrate for activation induced deaminase during somatic hypermutation. Xiaohua Wang, Manxia Fan, Susan Kalis, Lirong Wei, Matthew D. Scharff Nat. Communications 2014 Jun 13;5:4137. doi: 10.1038/ncomms5137.PMID: 24923561 PMCID: PMC4154566
37. Isotype switching increases efficacy of antibody protection against staphylococcal enterotoxin B-induced lethal shock and Staphylococcus aureus sepsis in mice.Varshney AK, Wang X, Aguilar JL, Scharff MD, Fries BC.MBio. 2014 Jun 10;5(3):e01007-14. doi: 10.1128/mBio.01007-14.PMID: 24917594 PMCID: PMC4056548
38. Generation, characterization, and epitope mapping of neutralizing and protective monoclonal antibodies against Staphylococcal enterotoxin B-induced lethal shock. Varshney AK, Wang X, Cook E, Dutta K, Scharff MD, Goger MJ, Fries BC. J Biol Chem. 2014 May 16;289(20):13706. doi: 10.1074/jbc.A110.212407. PMID: 25120261 PMCID: PMC4022843
39. Somatic Hypermutation: The molecular mechanisms underlying the production of effective high affinity antibodies; Alberto Martin, Richard Chahwan, Jahan Yar Parsa, Matthew D. Scharff:; Chapter 21 in the second edition of Molecular Biology of B Cells, edited by Tasuku Honjo, Fred Alt, Andreas Radbruch, and Michael Reth; Elsevier in Press 2014
40. Overlapping hotspots in CDRs are critical sites for V region diversification. Wei L, Chahwan R, Wang S, Wang X, Pham PT, Goodman MF, Bergman A, Scharff MD, MacCarthy T. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):E728-37. doi: 10.1073/pnas.1500788112. Epub 2015 Feb 2. PMCID: PMC4343087. Free PMC Article.
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