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Biochemical Assays

High Content Imaging

Imaging is at the forefront of our scientific artistry. Where we harness fluorescent tags to help highlight protein-protein interactions in vitro and ex vivo. As an extremely helpful tool for the process of drug discovery, high content imaging warrants clear visualization and comparison of phenotypic alterations that may be present in cell cultures. Thus, permitting concrete qualitative data and not to mention beautiful imagery. High throughput capture for both immunocytochemical and western blot purposes (Zeiss AxioScan, ProteinSimple Jess) has increasingly improved our workflow and project turnover. Check out our lab updates page to see some of the images we have been able to develop and capture in our research ventures.

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Human iPSC- derived neurons

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In Vivo Pharmacology

To understand the chemical underpinnings of a disease’s cellular pathology and mechanisms of action, in vivo pharmacology provides the ability to pull molecular hallmarks to the surface in measurable quantities which can yield pre-clinical information for potential treatments of cognitive diseases such as Frontotemporal Dementia (FTD), Progressive Supranuclear Palsy (PSP), and Alzheimer’s Disease (AD). Compound screening and validation using in vivo models of cognitive diseases has value in narrowing down molecular therapies for diseases treatment to provide precise therapy for these molecularly complicated diseases.
P301S mutant human tau transgenic mice have comparable behavioral, biochemical, and histological phenotypes to those of patients with Alzheimer’s Disease (AD). Using this transgenic animal line, Yoshiyama et al. 2007 has shown that not only do filamentous tau lesions develop in P301S mice at 6 months of age and progressively accumulates throughout their lifespan but also that hippocampal synapse loss and impaired synaptic function was detectable before tau tangles were present, consistent with human pathology. Our lab plans to employ this transgenic line to learn more about a class of targeted protein degraders, also known as Proteolysis Targeting Chimeras (PROTACS) that show promise in degradation of hyperphosphorylated tau aggregates (pathogenic tau). Recent work in our lab has shown that the PROTAC, QC-01-175, is successful in inducing ubiquitination and proteasomal degradation of pathogenic tau making this an exciting compound to test at an in vivo model. Click here to read more about the work done in our lab in regards to QC-01-175.

Medicinal Chemistry

Design, discovery, and optimization of small molecules is the name of the game. How is regeneration from diseased states possible? How can disease onset be prevented? These are the two main questions in mind when taking a deeper look into the neuro-genomic profile associated with a particular neurological disease. Analyzing how disease interrupts cellular/molecular pathways gives researchers a window to see where small molecules may be employed for therapeutic purpose. For example, previous work in the lab with HDAC inhibitors and Tau degraders have proved to be successful products of medicinal chemistry. Discovery of new and improved small molecules may continue to probe affected pathways in order to correct downstream ramifications attributable to disease.

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