William J. Simmons
New York University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by William J. Simmons.
Nature Medicine | 2005
Roberto Chiarle; William J. Simmons; Honjying Cai; Girish Dhall; Alberto Zamò; Regina Raz; James G. Karras; David E. Levy; Giorgio Inghirami
Anaplastic large cell lymphomas (ALCLs) are caused by chromosomal translocations that juxtapose the anaplastic lymphoma kinase (ALK) proto-oncogene to a dimerization partner, resulting in constitutive expression of ALK and ALK tyrosine kinase activity. One substrate of activated ALK in human ALCLs is the transcription factor Stat3, and its phosphorylation is accurately recapitulated in a new nucleophosmin (NPM)-ALK transgenic mouse model of lymphomagenesis. Here we show by gene targeting that Stat3 is required for the transformation of mouse embryonic fibroblasts in vitro, for the development of B-cell lymphoma in transgenic mice and for the growth and survival of both human and mouse NPM-ALK–transformed B and T cells. Ablation of Stat3 expression by antisense oligonucleotides significantly (P < 0.0001) impaired the growth of human and mouse NPM-ALK tumors in vivo. Pharmacological ablation of Stat3 represents a new candidate approach for the treatment of human lymphoma.
Cell Cycle | 2005
Giorgio Inghirami; Roberto Chiarle; William J. Simmons; Roberto Piva; Karni Schlessinger; David E. Levy
Signal transducers and activators of transcription (STAT) regulate a plethora of cytokine responses. Recently, aberrant signaling by STAT proteins has been demonstrated to play important roles in the pathogenesis of many neoplasms, by promoting cell cycle progression and survival, stimulating angiogenesis, and impairing immunological responses and tumor surveillance. We have developed genetic tools to evaluate STAT-dependent malignancy and showed that survival and growth of lymphoid malignancies requires expression of STAT3. In contrast, loss of STAT3 in normal cells does not impair their growth or survival; but in spite of this apparent dispensability of STAT3, STAT3-null fibroblasts are resistant to transformation by a variety of oncogenes. The precise molecular mechanisms responsible for the tumorigenic activity of STAT3 have been only partially elucidated. While the tyrosine phosphorylation of STAT3, which is indicative of its signal-dependent activation, is a common occurrence in tumors, and appears to play a crucial role in some malignancies, a variety of new data suggest that it can be dispensable under some circumstances and STAT3 can participate in transformation through novel and non-canonical mechanisms. The discovery and dissection of non-canonical modes of STAT3 action will open new avenues for the design of effective therapeutics capable of neutralizing the tumorigenic properties of this molecule.
Nature Biotechnology | 2009
William J. Simmons
Is the Federal Circuits decision in In re: Bilski yet a further restraint on patenting biotech and pharmaceutical inventions?
Journal of Immunology | 2003
Rajan M. Thomas; Kamran Haleem; Abu B. Siddique; William J. Simmons; Namita Sen; Da-Jun Zhang; Vincent K. Tsiagbe
Mammary tumor virus (Mtv29)-encoded superantigen expressed by SJL/J mouse B cell lymphomas stimulates CD4+Vβ16+ T cells and thereby acquires T cell help necessary for lymphoma growth. Mtv29 mouse mammary tumor virus env transcriptional activator (META) env-controlled Mtv29 superantigen (vSAg29) mRNA transcripts (1.8 kb) are not expressed in normal B or other somatic cells. Real-time PCR-based assays with DNA from normal SJL liver and vSAg29− lymphoma (cNJ101), digested with methylation-sensitive enzymes, showed hypermethylation at AvaI, FspI, HpaII, ThaI, and the distal HgaI sites of the META env, but vSAg29+ lymphoma cells showed significant demethylation at AvaI, HpaII, and the distal HgaI sites. The distal HgaI site that is adjacent to an Ikaros binding site is significantly demethylated in the META env DNA from primary lymphomas. Gel shift assays showed binding of Ikaros to a sequence representing this region in the META env. SJL lymphomas expressed the Ikaros isoform Ik6 that was absent in normal B cells. vSAg29+ cells exhibited increased DNaseI accessibility to chromatin at the vSAg29 initiation site. Treatment of cNJ101 cells with a demethylating agent, 5-azacytidine, and a histone deacetylase inhibitor, trichostatin A, caused hypomethylation at AvaI, HpaII, and distal HgaI sites and led to chromatin structural change at the vSAg29 initiation site, accompanied by the expression of vSAg29 transcripts. This enabled cNJ101 cells to stimulate SJL lymphoma-responsive CD4+Vβ16+ T hybridoma cells. Thus, demethylation at the distal HgaI site of the Mtv29 META env permits vSAg29 expression, which may have an impact on the development of germinal center-derived B cell lymphomas of SJL/J mice.
Nature Biotechnology | 2010
William J. Simmons
The court narrowly ruled that business methods may be patent eligible, while striking down the primacy of its main test.
Nature Biotechnology | 2004
William J. Simmons
Especially for biotechnology and pharmaceutical companies, the Madrid Protocol for international trademark registration marks a new era in trademark protection.
Blood | 2003
Roberto Chiarle; Jerald Z. Gong; Ilaria Guasparri; Anna Pesci; Jonjing Cai; Jian Liu; William J. Simmons; Girish Dhall; Jennifer Howes; Roberto Piva; Giorgio Inghirami
Blood | 2006
Roberto Piva; Roberto Chiarle; Andrea D. Manazza; Riccardo Taulli; William J. Simmons; Chiara Ambrogio; Valentina D'Escamard; Elisa Pellegrino; Carola Ponzetto; Giorgio Palestro; Giorgio Inghirami
Archive | 2013
Nicholas M. Ponzio; Giorgio Inghirami; Anthony J. Coyle; Scott Cutro; Parul Singh; William J. Simmons; Mythili Koneru; Mani Mohindru
Archive | 2010
Elisa Pellegrino; Carola Ponzetto; Giorgio Palestro; Roberto Piva; Roberto Chiarle; Andrea D. Manazza; Riccardo Taulli; William J. Simmons