Random Homozygous Gene Perturbation (RHGP) as a Tool for Target Discovery and Validation
Poster Sep 24, 2012
Wu-Bo Li and Michael Goldblatt
Random homozygous gene perturbation (RHGP) can identify and validate any host (cellular) gene target that directly causes a desired phenotype without requiring prior knowledge of the target. The central feature of RHGP is a unique lentiviral-based genetic element, known as a gene search vector (GSV) designed to interrogate the entire genome and identify target genes that cause the phenotype of interest. The GSV cassette contains an inducible promoter with an inducer response element (RE). The GSV is transduced into a target cell population that stably expresses the transactivator (TA). Transduction results in random integrations of the GSV into the genome of the target cells. In the presence of inducer, the TA binds the RE domain to activate the GSV promoter. Promoter activation triggers the transcription of the RNA extending into the host genome sequence flanking the 5´ LTR of the GSV. RHGP provides the ability to sample every gene in a cell for both over expression and loss of expression. When integrated in an antisense orientation, this event physically disrupts one allele, while producing antisense RNAs that knock down expression of the other allele. In the sense orientation, RHGP may overexpress the entire target gene when the vector is inserted upstream of the start site or overexpress the domains of the gene and produce a dominant-negative inhibitor of wild-type gene function. The inducible promoter of the GSV allows us to validate the candidates and eliminate false-positives that arise as a result of spontaneous mutation or other artifacts. With RHGP approach, FGI has successfully identified the host target genes involved in pathogenesis of cancer metastasis, drug resistance, Alzheimer’s Disease and viral infections. Therapeutics against the first of three RHGP identified targets for infectious disease is now in clinic trial. Therapeutics against the other two targets will be entering preclinical development shortly.
Mass Spectrometry: From Imaging to Metabolic NetworksPoster
We show that network analysis of co-localized ions from mass spectrometry imaging data provides a detailed chemo-spatial insight into the metabolic heterogeneity of tumor. Furthermore, module preservation analysis between colorectal cancer patients with and without metastatic recurrence suggests hypotheses on the nature of the different local metabolic pathways.READ MORE
Psychiatric Risk Gene Cacna1c and Early Life Stress: Potential Gene-Environment interactions?Poster
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
Treatment Options for Chronic Parvovirus Viremia in Pediatric Heart Transplant Patients in a Tertiary Care CenterPoster
This abstract discusses three cases of pediatric heart transplant patients who suffered from parvovirus (B19) infection. Of these patients, two ( B & C) responded well to standard intravenous Ig therapy. Patient A however, did not respond to standard treatment and was begun on subcutaneous Ig, which effectively diminished his viral load. Thus, subcutaneous Ig infusions might serve as a second line treatment for transplant patients with parvovirus who do not respond well to the standard approach.READ MORE
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27th International Conference on Nanomedicine and Nanomaterials
Oct 18 - Oct 19, 2018