Publications (68) View all
-
Article: Pharmacogenetic considerations for late life depression therapy.
[show abstract] [hide abstract]
ABSTRACT: Introduction: Geriatric depression is a heterogeneous disorder with a complex genetic background. Current first-line treatment of depression is associated with a lower therapeutic outcome in aged depressed patients, when compared to younger subjects. Research which has explored this inadequate response has highlighted several factors which have come into play with the pharmacogenetics of antidepressants in the elderly being a particular area of interest. Areas covered: The authors perform a critical review of the English language articles from PubMed using search terms such as late-life/geriatric depression, antidepressants, pharmacogenetics, pharmacogenomics, pharmacokinetic, genetic, genotype, remission, therapy, treatment and polymorphism. Expert opinion: The emerging clinical and pharmacogenetic data are slowly unveiling the importance of the genome - age interaction in antidepressant response. This data introduces a critical new parameter in personalized medicine. A profound analysis of the age factor in the pharmacogenetics of antidepressant response is imperative, in order to elucidate the clinical significance of these findings and thereby improve patient treatment in the elderly.Expert Opinion on Drug Metabolism & Toxicology 05/2013; · 3.12 Impact Factor -
Article: Reprogramming of the microRNA transcriptome mediates resistance to rapamycin.
[show abstract] [hide abstract]
ABSTRACT: The mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation, often deregulated in cancer. Inhibitors of mTOR, including rapamycin and its analogues, are being evaluated as anti-tumor agents. To fulfill their promise, it is of paramount importance to identify mechanisms of resistance and develop novel therapies to overcome it. Given the emerging role of microRNAs (miRNAs) in tumorigenesis we hypothesized that miRNAs could play important roles in the response of tumors to mTOR inhibitors. Long-term rapamycin treatment showed extensive reprogramming of miRNAs expression, characterized by up-regulation of the mir-17~92 and related clusters and down-regulation of tumorsuppressor miRNAs. Inhibition of members of mir-17~92 clusters or delivery of tumor suppressor miRNAs restored sensitivity to rapamycin. This study identified miRNAs as new downstream components of the mTOR-signaling pathway, which may determine the response of tumors to mTOR inhibitors. It also identifies potential markers to assess the efficacy of the treatment and provides novel therapeutic targets to treat rapamycin resistant tumors.Journal of Biological Chemistry 01/2013; · 4.77 Impact Factor -
Article: Combining multiple hypothesis testing and affinity propagation clustering leads to accurate, robust and sample size independent classification on gene expression data.
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: A feature selection method in microarray gene expression data should be independent of platform, disease and dataset size. Our hypothesis is that among the statistically significant ranked genes in a gene list, there should be clusters of genes that share similar biological functions related to the investigated disease. Thus, instead of keeping N top ranked genes, it would be more appropriate to define and keep a number of gene cluster exemplars. RESULTS: We propose a hybrid FS method (mAP-KL), which combines multiple hypothesis testing and affinity propagation (AP)-clustering algorithm along with the Krzanowski & Lai cluster quality index, to select a small yet informative subset of genes. We applied mAP-KL on real microarray data, as well as on simulated data, and compared its performance against 13 other feature selection approaches. Across a variety of diseases and number of samples, mAP-KL presents competitive classification results, particularly in neuromuscular diseases, where its overall AUC score was 0.91. Furthermore, mAP-KL generates concise yet biologically relevant and informative N-gene expression signatures, which can serve as a valuable tool for diagnostic and prognostic purposes, as well as a source of potential disease biomarkers in a broad range of diseases. CONCLUSIONS: mAP-KL is a data-driven and classifier-independent hybrid feature selection method, which applies to any disease classification problem based on microarray data, regardless of the available samples. Combining multiple hypothesis testing and AP leads to subsets of genes, which classify unknown samples from both, small and large patient cohorts with high accuracy.BMC Bioinformatics 10/2012; 13(1):270. · 2.75 Impact Factor -
Article: Interstitial colocalization of two cervid satellite DNAs involved in the genesis of the Indian muntjac karyotype
[show abstract] [hide abstract]
ABSTRACT: A number of repetitive DNA clones were generated from PCR amplifications of Indian muntjac genomic DNA using primer sequences derived from a white tailed deer satellite II DNA sequence. One clone (Mmv-0.7) was characterized and shown to be a cervid satellite II DNA clone. Multiple colored FISH studies with cervid satellite I (C5) and this satellite II clone (Mmv-0.7) to Chinese muntjac metaphase chromosomes localized both satellite DNAs at the pericentromeric regions of all chromosomes except for chromosome 3 and the Y chromosome, whereas chromosome 3 exhibited pericentromeric satellite II DNA only. Where distinguishable, the pericentromeric satellite II signals appeared terminally oriented with respect to satellite I. Six pairs of Chinese muntjac autosomes had interstitial satellite I sites with four of these autosomal pairs (chromosomes 1, 2 and two other smaller autosomal pairs) also exhibiting interstitial satellite II signals. An interstitial site on the X chromosome was found to have satellite II signals. For the Indian muntjac chromosomes, FISH studies revealed a pericentromeric hybridization for satellites I and II as well as 27 distinct interstitial hybridization sites, each having at least one of the satellite DNAs. These data were used to more precisely define the chromosome fusion-associated breakpoints that presumably led to the formation of the present-day Indian muntjac karyotype. It further hints at the possibility that the Indian muntjac karyotype may have evolved directly from a 2n=70 ancestral karyotype rather than from an intermediate 2n=46 Chinese muntjac-like karyotype.Chromosome Research 04/2012; 8(5):363-373. · 3.09 Impact Factor -
Chapter: Neuropharmacogenetics of Major Depression: Has the Time Come to Take both Sexes into Account?
03/2012; , ISBN: 978-953-51-0389-9
