Search results for: Philip Cohen

Items from 1 to 20 out of 148 results

article

The scientific career and life of Edmond H. Fischer—A personal tribute

Philip Cohen

IUBMB Life > 75 > 4 > 284 - 288

article

HOIL‐1‐catalysed, ester‐linked ubiquitylation restricts IL‐18 signaling in cytotoxic T cells but promotes TLR signalling in macrophages

Tsvetana Petrova, Jiazhen Zhang, Sambit K. Nanda, Clara Figueras‐Vadillo, more

The FEBS Journal > 288 > 20 > 5909 - 5924

The atypical E3 ligase HOIL‐1 forms ester bonds between ubiquitin and serine/threonine residues in proteins, but the physiological roles of this unusual modification are unknown. We now report that IL‐18 signalling leading to the production of interferon γ (IFNγ) and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) is enhanced in cytotoxic T cells from knock‐in mice expressing the E3 ligase‐inactive...

article

Predictors of Post-Operative Bleeding after Laparoscopic Sleeve Gastrectomy

Pei-Wen Lim, Jonathan Miller, Donald Czerniach, John Kelly, more

Surgery for Obesity and Related Diseases > 2016 > 12 > 7(S) > S213

article

Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling

Christoph H. Emmerich, Siddharth Bakshi, Ian R. Kelsall, Juanma Ortiz-Guerrero, more

Biochemical and Biophysical Research Communications > 2016 > 474 > 3 > 452-461

We have reported previously that activation of the MyD88-signaling network rapidly induces the formation of hybrid ubiquitin chains containing both Lys63-linked and Met1-linked ubiquitin (Ub) oligomers, some of which are attached covalently to Interleukin Receptor Associated kinase 1. Here we show that Lys63/Met1-Ub hybrids are also formed rapidly when the TNFR1/TRADD, TLR3/TRIF- and NOD1/RIP2-signaling...

article

Bill Whelan's impact on my life and career

Philip Cohen

Molecular Aspects of Medicine > 2015 > 46 > Complete > 11-13

In this tribute to Bill Whelan on his 90th birthday, I recount the huge impact that Bill has had on my life and career, and briefly recall the contributions that my laboratory made to the understanding of glycogenin in the late 1980s. In particular, the demonstration that glycogenin and glycogen synthase form a complex, and that glycogenin is a glucosyl transferase that autoglucosylates itself at...

article

Optineurin Negatively Regulates Osteoclast Differentiation by Modulating NF-κB and Interferon Signaling: Implications for Paget’s Disease

Rami Obaid, Sachin E. Wani, Asim Azfer, Toby Hurd, more

Cell Reports > 2015 > 13 > 6 > 1096-1102

Paget’s disease of bone (PDB) is a common disease characterized by osteoclast activation that leads to various skeletal complications. Susceptibility to PDB is mediated by a common variant at the optineurin (OPTN) locus, which is associated with reduced levels of mRNA. However, it is unclear how this leads to the development of PDB. Here, we show that OPTN acts as a negative regulator of osteoclast...

article

Optimising methods for the preservation, capture and identification of ubiquitin chains and ubiquitylated proteins by immunoblotting

Christoph H. Emmerich, Philip Cohen

Biochemical and Biophysical Research Communications > 2015 > 466 > 1 > 1-14

Immunoblotting is a powerful technique for the semi-quantitative analysis of ubiquitylation events, and remains the most commonly used method to study this process due to its high specificity, speed, sensitivity and relatively low cost. However, the ubiquitylation of proteins is complex and, when the analysis is performed in an inappropriate manner, it can lead to the misinterpretation of results...

article

An important role for A20-binding inhibitor of nuclear factor-kB-1 (ABIN1) in inflammation-mediated endothelial dysfunction: an in vivo study in ABIN1 (D485N) mice

Naveed Akbar, Sambit Nanda, Jill Belch, Philip Cohen, more

Arthritis Research & Therapy > 2015 > 17 > 1 > 1-10

Introduction The link between cardiovascular disease (CVD) and patients with chronic inflammation is not clearly understood. We examined a knock-in mouse expressing a poly-ubiquitin-binding-defective mutant of the protein ABIN1 (ABIN1(D485N)), which develops a systemic lupus erythematosus-like autoimmune disease because of the hyperactivation of IκB kinases (IκKs) and mitogen-activated protein...

article

TAK1 Inhibition in the DFG‐Out Conformation

Iain Kilty, Martin P. Green, Andrew S. Bell, David G. Brown, more

Chemical Biology & Drug Design > 82 > 5 > 500 - 505

The first example of an inhibitor of the kinase TAK1 that binds in the DFG‐out conformation is disclosed. These preliminary studies used kinase‐targeted screening and structure‐based drug design to create a molecule with dual pharmacological inhibition of p38 and TAK1 that demonstrated significant activity in a cell‐based, anti‐inflammatory assay.

article

The anti‐inflammatory compound BAY‐11‐7082 is a potent inhibitor of protein tyrosine phosphatases

Navasona Krishnan, Gyula Bencze, Philip Cohen, Nicholas K. Tonks

The FEBS Journal > 280 > 12 > 2830 - 2841

The families of protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) function in a coordinated manner to regulate signal transduction events that are critical for cellular homeostasis. Aberrant tyrosine phosphorylation, resulting from disruption of either PTP or PTK function, has been shown to be the cause of major human diseases, including cancer and diabetes. Consequently, the...

article

Rituximab Therapy for Primary Sjögren's Syndrome: An Open‐Label Clinical Trial and Mechanistic Analysis

E. William St.Clair, Marc C. Levesque, Eline T. Luning Prak, Frederick B. Vivino, more

Arthritis & Rheumatology > 65 > 4 > 1097 - 1106

ObjectiveTo study the safety and clinical efficacy of rituximab therapy for primary Sjögren's syndrome, as well as to investigate its mechanisms. MethodsPatients with primary Sjögren's syndrome were enrolled in an open‐label trial, were given rituximab (1 gm) infusions on days 1 and 15, and were monitored through week 52. The primary end point was safety, with secondary end points evaluating clinical...

article

Synthesis and structure–activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases

Edward G. McIver, Justin Bryans, Kristian Birchall, Jasveen Chugh, more

Bioorganic & Medicinal Chemistry Letters > 2012 > 22 > 23 > 7169-7173

The design, synthesis and structure–activity relationships of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative...

article

Indolent CD8‐positive T‐cell lymphoid proliferation of the ear: a report of two cases

Weifen Zeng, Victor E. Nava, Philip Cohen, Metin Ozdemirli

Journal of Cutaneous Pathology > 39 > 7 > 696 - 700

The current classification of primary cutaneous T‐cell lymphoma (CTCL) of the World Health Organization (WHO) includes primary cutaneous CD8‐positive aggressive epidermotropic cytotoxic T‐cell lymphoma as a provisional entity awaiting cumulative data. Recent reports identify CD3/CD8‐positive clonal T‐cell lymphoid proliferations arising in the ear and nose that behave indolently and therefore defy...

article

Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer

Claudine Isaacs, Pia Herbolsheimer, Minetta C. Liu, Mary Wilkinson, more

Breast Cancer Research and Treatment > 2011 > 125 > 1 > 137-143

We evaluated the use of sorafenib to overcome resistance to aromatase inhibitors (AIs) in patients with metastatic breast cancer who had disease recurrence or progression while on AIs. We performed a multi-institution phase I/II study of sorafenib and anastrozole 1 mg daily in 35 postmenopausal females with hormone receptor positive metastatic breast cancer resistant to AIs. Primary objectives were...

article

Will the Ubiquitin System Furnish as Many Drug Targets as Protein Kinases?

Philip Cohen, Marianna Tcherpakov

Cell > 2010 > 143 > 5 > 686-693

Protein phosphorylation and protein ubiquitination regulate most aspects of cell life, and defects in these control mechanisms cause cancer and many other diseases. In the past decade, protein kinases have become one of the most important classes of drug targets for the pharmaceutical industry. In contrast, drug discovery programs that target components of the ubiquitin system have lagged behind....

article

Synthesis, Pim kinase inhibitory potencies and in vitro antiproliferative activities of diversely substituted pyrrolo[2,3-a]carbazoles

Rufine Akué-Gédu, Lionel Nauton, Vincent Théry, Jenny Bain, more

Bioorganic & Medicinal Chemistry > 2010 > 18 > 18 > 6865-6873

The synthesis of new pyrrolo[2,3-a]carbazole derivatives diversely substituted at the C-6 to C-9 positions is described. These compounds were tested for their kinase inhibitory potencies toward three kinases (Pim-1, Pim-2, Pim-3) as well as for their in vitro antiproliferative activities toward a human fibroblast primary culture and three human solid cancer cell lines (PC3, DU145, and PA 1). Moreover,...

article

P-78: Impact of a hospital-based midlevel provider on patient outcomes after roux-en-Y gastric bypass in a high volume center

Donald R. Czerniach, Richard A. Perugini, Melissa McDonald, Karen A. Gallagher-Dorval, more

Surgery for Obesity and Related Diseases > 2010 > 6 > 3 Supplement > S54-S55

article

A New Compact for Higher Education: Funding and Autonomy for Reform and Accountability

James M. Kallison, Philip Cohen

Innovative Higher Education > 2010 > 35 > 1 > 37-49

Over the past few decades, America’s social compact for higher education as a public good has effectively lapsed as government support of higher education has diminished. Given the need for a highly educated workforce in today’s knowledge-based global economy, we propose a new compact for higher education that couples increased funding with increased institutional accountability. While the compact...

article

Synthesis, Kinase Inhibitory Potencies, and in Vitro Antiproliferative Evaluation of New Pim Kinase Inhibitors

Rufine Akué-Gédu, Emilie Rossignol, Stéphane Azzaro, Stefan Knapp, more

Journal of Medicinal Chemistry > 2009 > 52 > 20 > 6369 - 6381

article

Targeting protein kinases for the development of anti-inflammatory drugs

Philip Cohen

Current Opinion in Cell Biology > 2009 > 21 > 2 > 317-324

In recent years, protein kinases have become the pharmaceutical industry's most studied class of drug target, and some 10 protein kinase inhibitors have so far been approved for the treatment of cancer. However, whether safe drugs that modulate protein kinase activities can also be developed for the treatment of chronic diseases, where they may need to be taken for decades, is an issue that is still...

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INFONA - science communication portal

Search results for: Philip Cohen

The scientific career and life of Edmond H. Fischer—A personal tribute

HOIL‐1‐catalysed, ester‐linked ubiquitylation restricts IL‐18 signaling in cytotoxic T cells but promotes TLR signalling in macrophages

Predictors of Post-Operative Bleeding after Laparoscopic Sleeve Gastrectomy

Lys63/Met1-hybrid ubiquitin chains are commonly formed during the activation of innate immune signalling

Bill Whelan's impact on my life and career

Optineurin Negatively Regulates Osteoclast Differentiation by Modulating NF-κB and Interferon Signaling: Implications for Paget’s Disease

Optimising methods for the preservation, capture and identification of ubiquitin chains and ubiquitylated proteins by immunoblotting

An important role for A20-binding inhibitor of nuclear factor-kB-1 (ABIN1) in inflammation-mediated endothelial dysfunction: an in vivo study in ABIN1 (D485N) mice

TAK1 Inhibition in the DFG‐Out Conformation

The anti‐inflammatory compound BAY‐11‐7082 is a potent inhibitor of protein tyrosine phosphatases

Rituximab Therapy for Primary Sjögren's Syndrome: An Open‐Label Clinical Trial and Mechanistic Analysis

Synthesis and structure–activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases

Indolent CD8‐positive T‐cell lymphoid proliferation of the ear: a report of two cases

Phase I/II study of sorafenib with anastrozole in patients with hormone receptor positive aromatase inhibitor resistant metastatic breast cancer

Will the Ubiquitin System Furnish as Many Drug Targets as Protein Kinases?

Synthesis, Pim kinase inhibitory potencies and in vitro antiproliferative activities of diversely substituted pyrrolo[2,3-a]carbazoles

P-78: Impact of a hospital-based midlevel provider on patient outcomes after roux-en-Y gastric bypass in a high volume center

A New Compact for Higher Education: Funding and Autonomy for Reform and Accountability

Synthesis, Kinase Inhibitory Potencies, and in Vitro Antiproliferative Evaluation of New Pim Kinase Inhibitors

Targeting protein kinases for the development of anti-inflammatory drugs

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