Arthur L. Shaffer III, Ph.D.

Arthur L. Shaffer III, Ph.D.
Staff Scientist

My primary interests are 1) using gene expression profiling to understand normal and malignant B cell differentiation, and 2) developing novel assays and therapeutics for the diagnosis and treatment of B cell lymphoma.

Areas of Expertise
1) gene expression 2) lymphoma genomics 3) mechanisms of drug resistance

Contact Info

Arthur L. Shaffer III, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 10, Room 6N105
Bethesda, MD 20892
Ph: 301-496-8890

- Use gene expression profiling to understand normal and malignant B cell differentiation. 

- Develop novel assays and therapeutics for the diagnosis and treatment of B cell lymphoma. 

- Develop tools for the analysis of gene expression data.

Selected Publications

  1. Schmitz R1, Wright GW1, Huang DW1, Johnson CA1, Phelan JD1, Wang JQ1, Roulland S1, Kasbekar M1, Young RM1, Shaffer AL1, Hodson DJ1, Xiao W1, Yu X1, Yang Y1, Zhao H1, Xu W1, Liu X1, Zhou B1, Du W1, Chan WC1, Jaffe ES1, Gascoyne RD1, Connors JM1, Campo E1, Lopez-Guillermo A1, Rosenwald A1, Ott G1, Delabie J1, Rimsza LM1, Tay Kuang Wei K1, Zelenetz AD1, Leonard JP1, Bartlett NL1, Tran B1, Shetty J1, Zhao Y1, Soppet DR1, Pittaluga S1, Wilson WH1, Staudt LM1.
    N Engl J Med. 2018 Apr 12;378(15):1396-1407: 2018. [ Journal Article ]
  2. Phelan JD1, Young RM1, Webster DE1, Roulland S1,2, Wright GW3, Kasbekar M1, Shaffer AL 3rd1, Ceribelli M4, Wang JQ1, Schmitz R1, Nakagawa M1, Bachy E1, Huang DW1, Ji Y5, Chen L4, Yang Y1, Zhao H1, Yu X1, Xu W1, Palisoc MM6, Valadez RR6, Davies-Hill T6, Wilson WH1, Chan WC7, Jaffe ES6, Gascoyne RD8, Campo E9, Rosenwald A10, Ott G11, Delabie J12, Rimsza LM13, Rodriguez FJ14, Estephan F15, Holdhoff M15, Kruhlak MJ16, Hewitt SM17, Thomas CJ1,4, Pittaluga S6, Oellerich T1,5,18, Staudt LM19.
    Nature. Nature. 2018 Jun 20. doi: 10.1038/s41586-018-0290-0.: 2018. [ Journal Article ]
  3. Shaffer AL, Young RM, Staudt LM.
    Annu. Rev. Immunol. 30: 565-610, 2012. [ Journal Article ]
  4. Yang Y, Shaffer AL, Emre NC, Ceribelli M, Zhang M, Wright G, Xiao W, Powell J, Platig J, Kohlhammer H, Young RM, Zhao H, Yang Y, Xu W, Buggy JJ, Balasubramanian S, Mathews LA, Shinn P, Guha R, Ferrer M, Thomas C, Waldmann TA, Staudt LM.
    Cancer Cell. 21: 723-37, 2012. [ Journal Article ]
  5. Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, Kohlhammer H, Xu W, Yang Y, Zhao H, Shaffer AL, Romesser P, Wright G, Powell J, Rosenwald A, Muller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Staudt LM.
    Nature. 470: 115-9, 2011. [ Journal Article ]

Dr. Shaffer has a fundamental interest in the application of basic immunology to problems involving the dysregulation of the immune system, especially with regard to cancer. He developed his abiding interest in basic immunology as a graduate student at Johns Hopkins under the tutelage of then new faculty member Mark Schlissel, studying the targeting and timing of V(D)J recombination during early B cell development. Continuing to pursue his interest in understanding the interplay of normal and pathological immune system development, Dr. Shaffer became a post-doctoral fellow in the laboratory of Dr. Louis Staudt in the National Cancer Institute in 1996. His first effort was to uncover the genes lying downstream of a transcriptional repressor, BCL6, which is not only essential for normal germinal B cell differentiation but is also a target of recurrent translocations in diffuse large B cell lymphoma, a malignancy of germinal center B cells. Employing the then-novel technology of gene expression microarrays developed in the Staudt lab, Dr. Shaffer found that BCL6 represses genes involved in B cell activation, inflammation, and terminal plasmacytic differentiation, thereby enforcing the germinal center B cell program. Dr. Shaffer made a fundamental insight into the pathogenesis of diffuse large B cell lymphoma by demonstrating that BCL-6 represses Blimp-1, an essential regulator of plasmacytic differentiation. Normally, BCL-6 is silenced during plasmacytic differentiation, but translocations in diffuse large B cell lymphoma prevent this. BCL-6 expression in these lymphomas blocks Blimp-1, thereby trapping the malignant B cells at an intermediate stage of differentiation, halfway between the germinal center B cell and the plasma cell. Such diffuse large B cell lymphomas, known as the activated B cell-like (ABC) subtype, have a plasmablastic phenotype, express AID highly, and accumulate a variety of other cooperating oncogenic mutations. After this initial success in combining gene expression profiling and the study of B cell differentiation, Dr. Shaffer went on to elucidate the action of several additional critical B cell differentiation-related transcription factors. His work, along with the efforts of many excellent collaborators has shown that: - the critical plasma cell transcriptional repressor, Blimp-1, shuts down the B cell gene expression program and forms a negative feedback loop with BCL6 to lock cells into a terminally differentiated state. - the plasma cell transcriptional activator, XBP1, is a master regulator of the secretory system and, surprisingly, also increases cell size and protein translation, allowing for maximal antibody synthesis. - the transcription factor IRF4 coordinates B cell isotype switching and initiates plasma cell differentiation by inducing critical regulators of these processes, including AID and Blimp-1. As a result of these experimental successes as a post-doc, Dr. Shaffer was appointed as a Staff Scientist in 2001, and has enjoyed connecting with the broader NIH immunology community through the Immunology Interest Group and the late, lamented B cell Workshop. He remains fundamentally convinced of the pre-eminence of the alphabetically superior lymphocyte.