Within the NTDU group, we continue to utilize a number of automated, medium throughput assays to screen small compound collections against rat mixed cortical cultures, human neural stem cells (NSC) and human NSC-derived neurons and astrocytes. Weve utilized live cell imaging based assays with rat hippocampal and human neurons, as well as developed fluorescence-based assays to probe high content imaging endpoints. These cell based screening assays, in 384 well plate format, have been successfully employed in multiple screens with multiple investigators. We have continued to generate new chemical tool compounds in our chemistry labs to facilitate screening and mechanistic studies in our research projects. We produce and purify a number of recombinant proteins, such as Cdk5 and the HIV Tat protein for our own studies and provide that Tat protein to extramural researchers around the world for their studies. With the Section of Infections of the Nervous System (SINS), we have continued to work on multiple research projects. We continue to characterize the neurotoxicity resulting from the expression of the HERV-K env protein in NSC and human neurons, and have already identified some compounds which attenuate HERVK env mediated neurotoxicity . We have recently begun to characterize the toxic actions of Zika virus on neural cells. The HIV Tat antagonist program has incorporated direct label-free binding assays as well as Tat-dependent selective LTR activation assays to complete the screening of more than 2000 compounds to identify new lead Tat inhibitors. The NTDU has continued a number of studies in collaboration with other intramural investigators. We continue to work with Dr. Harish Pant and his research team to characterize the neuroprotective actions of the Cdk5 modulator TFP-5. Treatment of neural stem cells with TFP-5 or analogs like TP5 robustly accelerated neuronal differentiation in a concentration dependent manner with low nanomolar potency. Likewise, we continue to work with the Sibley research group to characterize the dopamine D3 receptor agonists that they have identified, using our live cell imaging platforms for quantitative analysis. We have recently begun working with two clinical investigators, Drs. Paul Lee and Michael Ward in screening projects involving new iPSC lines and their derived neurons and astrocytes. We have also worked closely with the Dr. Francis McMahon laboratory to generate fluorescently labeled NSC and neuronal cultures from control and neuropsychiatric patients, to characterize their morphologic changes in response to stressors or toxic challenges.
| Steiner, Joseph P; Bachani, Muznabanu; Wolfson-Stofko, Brett et al. (2016) Erratum to: Interaction of Paroxetine with Mitochondrial Proteins Mediates Neuroprotection. Neurotherapeutics 13:237 |
| Meulendyke, Kelly A; Queen, Suzanne E; Engle, Elizabeth L et al. (2014) Combination fluconazole/paroxetine treatment is neuroprotective despite ongoing neuroinflammation and viral replication in an SIV model of HIV neurological disease. J Neurovirol 20:591-602 |
| Nath, Avindra; Steiner, Joseph (2014) Synaptodendritic injury with HIV-Tat protein: What is the therapeutic target? Exp Neurol 251:112-4 |
| Malik, Nasir; Efthymiou, Anastasia G; Mather, Karly et al. (2014) Compounds with species and cell type specific toxicity identified in a 2000 compound drug screen of neural stem cells and rat mixed cortical neurons. Neurotoxicology 45:192-200 |
