Derek Murphy

Marino Institute of Education · Trinity International Foundation Programme

FAS-associated protein with death domain (FADD) is a major adaptor protein involved in extrinsic apoptosis, embryogenesis, and lymphocyte homeostasis. Although abnormalities of the FADD/death receptor apoptotic pathways have been established in tumorigenesis, fewer studies have analyzed the expression and role of phosphorylated FADD (pFADD). Our id...

Correction to: Leukemia (2014) 28, 362-372; doi:10.1038/leu.2013.224; published online 13 August 2013 Since the publication of this article, the authors have identified an error contained in Figure 6 (panel c). FOXP1hi/HIP1Rlo has been incorrectly listed as FOXP1hi/HIP1Rhi. The correct figure appears below. (Figure presented) The error has now been...

We previously identified autoantibodies to the endocytic-associated protein Huntingtin interacting protein 1-related (HIP1R) in diffuse large B-cell lymphoma (DLBCL) patients. HIP1R regulates internalization of cell surface receptors via endocytosis, a process relevant to many therapeutic strategies including CD20 targeting with rituximab. In this...

Characterising tumour-associated antigens (TAAs) not only represents an important approach to the identification of new diagnostic/prognostic markers, but can also provide information on disease processes and additional potential therapeutic targets. Preliminary screening of a protein macroarray, containing more than 12,000 different proteins, with...

Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns...

(A) Expression of AURKA mRNA 48 hours post PTPRD expression. Either 1 μg of PTPRD or empty vector (E.V.) were transfected into Kelly cells. mRNA was extracted at 48 hours and qPCR was performed. The figure is representative of four independent experiments and E.V. is set as 1.0. (B) Expression of MYCN mRNA 48 hours post PTPRD expression. Either 1 μ...

Expression of PTPRD (A) mRNA and (B) protein following transfection of Kelly cells with increasing concentrations of PTPRD cDNA. mRNA was extracted at 24 hours and qPCR was performed. Lysates were harvested at 48 h and subjected to SDS PAGE and western blot analysis with a monoclonal antibody to the V5 epitope tag or alpha tubulin. All experiments...

Reactive oxygen species generation is one consequence of ligand engagement of platelet glycoprotein (GP) receptors GPIb-IX-V and GPVI, which bind VWF/collagen and initiate thrombosis at arterial shear; however, the precise molecular mechanism coupling redox pathway activation to engagement of these receptors is unknown. The objective of this study...

Integrins are transmembrane proteins regulating cellular shape, mobility and the cell cycle. A highly conserved signature motif in the cytoplasmic tail of the integrin alpha-subunit, KXGFFKR, plays a critical role in regulating integrin function. To date, six proteins have been identified that target this motif of the platelet-specific integrin alp...

Complex repertoires of IgG autoantibodies have been detected against ocular antigens in patients with glaucoma. The goal was to identify and characterize the IgG autoantibody repertoires in sera of patients with pseudoexfoliation glaucoma (PXFG) with protein macroarrays. Serum samples of 21 patients with PXFG and 19 age- and sex-matched control sub...

We have previously reported a novel constitutively overexpressed 21 kDa protein in Hodgkin Lymphoma (HL) and aggressive Non-Hodgkin Lymphomas (NHL). The objective of the current study was to 1) identify this protein using two independent methods, 2) study the expression of the protein and its encoding mRNA in reactive lymph nodes, normal lymphocyte...

Many diagnostic antibodies are generated by immunization with whole cells or cell extracts and are shown by screening on tissue sections to label specific cell populations. However, their target molecule then needs to be identified, and this can be technically demanding. Here we describe the use of protein arrays to define the targets of new or unc...

Patients with cancer have antibodies against tumour antigens. Characterising the antibody repertoire may provide insights into aberrant cellular mechanisms in cancer development, ultimately leading to novel diagnostic or therapeutic targets. The aim of this study was to characterise the antibody profiles in patients whose symptoms warranted colonos...

Protein array technology has begun to play a significant role in the study of protein-protein interactions and in the identification of antigenic targets of serum autoantibodies in a variety of autoimmune disorders. More recently, this technology has been applied to the identification of autoantibody signatures in cancer. The identification of tumo...

Antibodies are routinely used as research tools, in diagnostic assays and increasingly as therapeutics. Ideally, these applications require antibodies with high sensitivity and specificity; however, many commercially available antibodies are limited in their use as they cross-react with non-related proteins. Here we describe a novel method to chara...

The volume-regulating protein, ICln, interacts with the conserved KxGFFKR alpha-integrin signature motif. ICln is an abundant protein (4455 +/- 650 molecules/platelet) found exclusively in the soluble cytosolic fraction of unactivated platelets. In contrast, its binding partner, the platelet integrin alpha(IIb)beta(3), is present in detergent-insol...

We screened lymphoma patients’ serum samples against protein/antigen arrays, containing over 10,000 different human proteins, to identify disease-associated auto-IgG antibody interactions. This approach identified a humoral immune response to the HIP1R antigen in 40% of patients’ sera (4/6 follicular lymphomas, 3/5 germinal centre [GC]-derived diff...

Over thirty types of lymphoma are now recognized and correct diagnosis is therefore essential. We have developed a novel approach, using arrays containing thousands of recombinant proteins (Bussow K, Cahill D, Nietfeld W et al. Nucleic Acids Res 1998 26:5007–8; Gutjahr C, Murphy D, Lueking A et al. Genomics 2005 85:285–96), to identify new potentia...

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by progressive depression of myocardial contractile function and ventricular dilatation. Thirty percent of DCM patients belong to the inherited genetic form; the rest may be idiopathic, viral, autoimmune, or immune-mediated associated with a viral infection. Disturbances in humoral...

During the course of raising monoclonal antibodies, reagents are often produced that are not directed against the immunising antigen. These may pass unnoticed unless a screening step based on immunostaining of human tissue is included. Many of these reagents are auto-antibodies, often directed against intracellular targets (e.g. nuclear components)...

Protein array technology is becoming an increasingly important tool in the drive toward proteome-scale analysis of protein activity and interactions. Presently, this technology compliments the more traditional methods for proteomic analysis, including two-dimensional gel electrophoresis/chromatography and mass spectrometry. While the task of produc...

Protein array technology is becoming an increasingly important tool in the drive toward proteome-scale analysis of protein activity and interactions. Presently, this technology compliments the more traditional methods for proteomic analysis, including two-dimensional gel electrophoresis/chromatography and mass spectrometry. While the task of produc...

The mouse is the premier genetic model organism for the study of disease and development. We describe the establishment of a mouse T helper cell type 1 (T(H)1) protein expression library that provides direct access to thousands of recombinant mouse proteins, in particular those associated with immune responses. The advantage of a system based on th...

A critical role for the conserved alpha-integrin cytoplasmic motif, KVGFFKR, is recognized in the regulation of activation of the platelet integrin alpha(IIb)beta(3). To understand the molecular mechanisms of this regulation, we sought to determine the nature of the protein interactions with this cytoplasmic motif. We used a tagged synthetic peptid...

There is no effective treatment for advanced hepatocellular carcinoma (HCC). We therefore explored the molecular mechanisms of interferon-gamma (IFN-gamma)-mediated growth regulation in human HCC cell lines. IFN-gamma receptor expression, signal transduction, and regulation of effectors were examined by RT-PCR, immunoprecipitation, immunoblotting,...

With the advent of protein and antibody microarray technology several different coatings and protocols have been published, which may be broadly divided into two types: gel-coated surfaces and plain non-gel-coated glass or plastic surfaces, some with chemical groups attached. We have screened 11 different array surfaces of both types and compared t...

The potential antiproliferative effects of interferon-alpha (IFN-alpha) in the treatment of hepatocellular carcinoma (HCC) are controversial, and the growth inhibitory mechanisms remain poorly understood. Therefore, the current study was designed to delineate the molecular mechanisms responsible for direct antiproliferative actions of IFN-alpha in...

The tumor suppressor gene p16(INK4a) inhibits the kinase activity of the cyclin-dependent kinase 4-6/cyclin D complexes and subsequent phosphorylation of critical substrates necessary for transit through the G1 phase of the cell cycle. Recent studies suggested that control of the G1/S boundary might not be the sole biological function of p16(INK4a)...

The tumor suppressor gene p16INK4a inhibits the kinase activity of the cyclin-dependent kinase 4–6/cyclin D complexes and subsequent phosphorylation of critical substrates necessary for transit through the G1 phase of the cell cycle. Recent studies suggested that control of the G1/S boundary might not be the sole biological function of p16INK4a. We...

We describe the isolation and characterization of the cDNA for FKHL13, the human homologue of the mouse hepatocyte nuclear factor 3/fork head homologue 4 (HFH-4) gene, a member of the HNF-3/fork head (also called winged helix) gene family. Members of this gene family contain a conserved DNA binding region of approx. 110 amino acids and are thought...

Analysis of cDNA clones, isolated from a human fetal brain cDNA library, that hybridized with the rat HNF-3 alpha fork head homolog domain revealed the 3.6-kb HFKL5 cDNA. The transcript of HFKL5 is 4.4 kb long and represents a novel member of the HNF-3/fork head transcription factor family. Comparison of the amino acid sequence of the fork head dom...

Analysis of cDNA clones, isolated from a human fetal brain cDNA library, that hybridized with the rat HNF-3 alpha fork head homolog domain revealed the 3,6-kb HFKL5 cDNA, The transcript of HFKL5 is 4.4 kb long and represents a novel member of the HNF-3/fork head transcription factor family, Comparison of the amino acid sequence of the fork head dom...

Of all the techniques available for microassisted reproduction, the direct injection of individual sperm cells or spermatids into the cytoplasm of the oocyte (ICSI) is the most invasive, through which any possible selection against sperm cells with genomic defects would be excluded. It has, however, been shown that such a possible selection is pres...

The mitochondrial capsule selenoprotein (MCS) (HGMW-approved symbol MCSP) is one of three proteins that are important for the maintenance and stabilization of the crescent structure of the sperm mitochondria. We describe here the isolation of a cDNA, the exon-intron organization, the expression, and the chromosomal localization of the human MCS gen...

The mitochondrial capsule selenoprotein (MCS) is a selenium-containing polypeptide. It is one of three proteins that are important for the maintenance and stabilization of the crescent structure of the sperm mitochondria. In this paper, we report the isolation and characterization of the rat MCS cDNA and gene. The cDNA contains a reading frame for...

Brain factor-1 (BF-1) is a member of the fork head gene family which shows expression restricted to the neurons of the developing telencephalon in rodents and man. We have isolated a second human gene (HBF-2), which is also strongly expressed in embryonic brain and has very high homology to both the rat and human brain factor-1 genes and the retrov...

Brain factor-1 (BF-1) is a member of the fork head gene family which shows expression restricted to the neurons of the developing telencephalon in rodents and man. We have isolated a second human gene (HBF-2), which is also strongly expressed in embryonic brain and has very high homology to both the rat and human brain factor-1 genes and the retrov...

cDNA clones for the human Leydig insulin-like peptide (Ley I-L) have been isolated and characterized. The nucleotide sequence of the 743-bp cDNA includes an incomplete 7-bp 5'-noncoding region, an open reading frame of 393 bp, and a 343-bp 3'-noncoding region. By primer extension analysis, the transcription start site was determined as being 14-bp...

Analysis of cDNA clones that cross-hybridized with the fork head domain of the rat HNF-3 gene family revealed 10 cDNAs from human fetal brain and human testis cDNA libraries containing this highly conserved DNA-binding domain. Three of these cDNAs (HFK1, HFK2, and HFK3) were further analyzed. The cDNA HFK1 has a length of 2557 nucleotides and shows...