Biomedical subjects

Ross Taplin

Publications and source records attributed to Ross Taplin.

3 recordsLinked to original sources

PubMed2005

Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals.

Gene expression profiling was performed on biopsies of affected and unaffected psoriatic skin and normal skin from seven Japanese patients to obtain insights into the pathways that control this disease. HUG95A Affymetrix DNA chips that contained oligonucleotide arrays of approximately 12,000 well-characterized human genes were used in the study. The statistical analysis of the Affymetrix data, based on the ranking of the Student t-test statistic, revealed a complex regulation of molecular stress and immune gene responses. The majority of the 266 induced genes in affected and unaffected psoriatic skin were involved with interferon mediation, immunity, cell adhesion, cytoskeleton restructuring, protein trafficking and degradation, RNA regulation and degradation, signalling transduction, apoptosis and atypical epidermal cellular proliferation and differentiation. The disturbances in the normal protein degradation equilibrium of skin were reflected by the significant increase in the gene expression of various protease inhibitors and proteinases, including the induced components of the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved with peptide processing and presentation to T cells. Some of the up-regulated genes, such as TGM1, IVL, FABP5, CSTA and SPRR, are well-known psoriatic markers involved in atypical epidermal cellular organization and differentiation. In the comparison between the affected and unaffected psoriatic skin, the transcription factor JUNB was found at the top of the statistical rankings for the up-regulated genes in affected skin, suggesting that it has an important but as yet undefined role in psoriasis. Our gene expression data and analysis suggest that psoriasis is a chronic interferon- and T-cell-mediated immune disease of the skin where the imbalance in epidermal cellular structure, growth and differentiation arises from the molecular antiviral stress signals initiating inappropriate immune responses.

Adult↗

PubMed2004

A microarray model system identifies potential new target genes of the proto-oncogene HOX11.

HOX11 is a homeobox gene originally identified at a chromosomal breakpoint in T-cell acute lymphoblastic leukemia (T-ALL). It is one of the most frequently deregulated genes in T-ALL, although the precise role of HOX11 in leukemogenesis as well as in normal development remains obscure. To gain more insight into the functional role of HOX11, we utilized a microarray model system to characterize the gene expression network that it directs. Using one of our T-ALL cell lines that had been stably transfected to express HOX11 and high-density oligonucleotide HG-U95A arrays, we identified a large number of differentially expressed genes in response to the enforced expression of HOX11. We focused on examining genes found to be up-regulated according to the microarray analysis and selected three putative target genes, NFKB2, SMARCD3, and NR4A3, for further investigation. We could not only confirm the up-regulation of NR4A3 by an independent method in all clones expressing HOX11, but luciferase reporter assays demonstrated that the effect that HOX11 exerted on the proximal promoter of NR4A3 was dependent on the presence of an intact homeodomain, providing support for the idea that HOX11 manifests its regulatory function via its action as a transcription factor.

Cell Line, Tumor↗

PubMed2003

Gap mapping: a paradigm for aligning two sequences.

Pairwise sequence alignment is one of the most essential tools in comparative genomic sequence analysis. It is used to compare the sequences of genes and proteins with the aim of inferring structural, functional and evolutionary relationships. However, current 'mainstream' alignment algorithms have optimisation criteria based primarily on computational efficiency using parameters such as gap penalties, which are not biologically motivated. In addition, current alignment algorithms such as the Smith and Waterman technique provide a single alignment that could be sensitive to rather arbitrary choices in parameters such as gap penalties. This paper explores the range of properties resulting from posing the alignment problem more as a 'mapping gaps in sequences' exercise. We argue that this approach is intuitive and provides greater control over the number of gaps placed within an alignment. This type of approach was proposed by Sankoff (1972), but unfortunately has not received much attention. We report and discuss our findings by comparing this approach to other techniques using structurally confirmed aligned sequences from a benchmark alignment database. Interestingly, this approach consistently provides optimal and near optimal alignments and is thus a viable approach to sequence alignment.

Algorithms↗