Northwestern University

Feb
25
Mon 4:00 PM

Pharmacology Research Works-in-Progress: Chuyu Chen, Ph.D. and Eugene Wyatt, Ph.D.

When: Monday, February 25, 2019
4:00 PM - 5:00 PM  

Where: Ward Building, 5-230, 303 E. Chicago Avenue, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Alexa Nash   312.503.4893

Group: Department of Pharmacology Seminars

Category: Lectures & Meetings

Description:

Chuyu Chen, Ph.D.
Postdoctoral Fellow, Dr. Loukia Parisiadou Laboratory

“Parkinson’s Disease Related LRRK2 Regulates Striatal Intracellular Signaling Cascades”

Mutations in LRRK2 represent a strong genetic risk for both hereditary and sporadic forms of Parkinson’s disease. Therefore, knowledge on LRRK2 function might be leveraged for therapeutic benefit. LRRK2 is significantly enriched in spiny projection neurons (SPN) in the dorsal striatum. This cellular expression pattern argues that LRRK2 mutations contribute to striatal pathophysiology in PD. Our previous findings demonstrate that LRRK2 regulates glutamatergic synaptic functions by directing PKA signaling in SPNs, whereas the LRRK2R1441C pathogenic mutation results in increased synaptic PKA activities. As PKA pathway is the critical effector of dopamine receptors, we showed that this aberrant PKA activity in LRRK2R1441C SPNs leads to perturbations in dopaminergic and corticostriatal signaling. We propose that altered subcellular compartmentalization of PKA imposed by the LRRK2R1441C mutation is the central mechanism for aberrant PKA signaling in SPNs. In the present study, using a series of super-resolution, structured illumination microscopy (SIM) imaging and PKA sensors we show how PKA localization shapes PKA activity in pathway-specific (direct and indirect) mutant LRRK2 SPNs. Specifically, we determine whether the effect of LRRK2 on PKA localization results in increased PKA availability to synaptic A-kinase anchoring protein 5 (AKAP5), suggesting a direct contribution of AKAP5 to LRRK2-related phenotypes. Overall, our study provides mechanistic insights of LRRK2-mediated cellular deficits in the striatum that in turn contributes to PD symptomatology.

Eugene Wyatt, Ph.D.
Research Assistant Professor of Pharmacology

"Generating Mouse Models Through the Northwestern TTML"

Genetically modified mice are essential research tools used to understand gene function and model disease. The advent of CRISPR gene editing technology has revolutionized the process of generating mouse models, reducing costs and improving efficiency. The Northwestern University Transgenic and Targeted Mutagenesis Laboratory (TTML) has extensive experience using the most cutting-edge CRISPR gene editing techniques to generate genetically modified mice. This includes knock-outs, point mutations, insertion of epitope tags, and conditional alleles. The TTML offers project design consultation, and can target mutations in embryos and embryonic stem cells. In addition, the TTML offers a comprehensive range of services for the Northwestern community.

Add Event to Calendar

Add Event To My Group:

Please sign-in