Northwestern University

Jan
28
Mon 4:00 PM

Pharmacology Research Works-in-Progress: Rama Mishra, Ph.D. and Mehdi Maneshi, Ph.D.

When: Monday, January 28, 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:

Rama Mishra, Ph.D.
Research Assistant Professor of Pharmacology
Center for Molecular Innovation and Drug Discovery

"Accelerating Drug Discovery Research Through In-Silico Methods"

In-Silico drug discovery approaches are broadly divided into ligand- (or cheminformatics) and structure-based methodologies. Though these two approaches are based on very different algorithms, both are employed towards similar goals of identifying or designing in-silico hits from the chemical libraries containing billions of drug-like molecules; estimating the binding affinity ( IC50/ Ki /Kd) ; and predicting the binding poses of the molecules if the 3D- structure of the disease protein target is known. In spite of obvious commonality of many of their goals between the two approaches, the methods have been viewed and applied independently. In this talk, I will focus on the integration of the two methods at the technical and functional levels. At the technical level, I will show the experimental validations of the in-silico predicted results, while at the functional level; I will talk about our participation with the drug discovery research community of Northwestern University.

Mehdi Maneshi, Ph.D.
Postdoctoral Fellow, Dr. Murali Prakriya Laboratory

"Regulation of Ca2+ signaling and synaptic plasticity in dendritic spines by Orai1"

Calcium signaling plays a crucial role in synaptic plasticity and Long-Term Potentiation (LTP) and has been shown to be altered in disease state such as in Alzheimer’s disease. An essential and highly conserved Ca2+ signaling pathway in many cells is store operated calcium entry (SOCE). SOCE is mediated by the well described Orai family of channels, yet the role of Orai channels for synaptic plasticity has not been addressed. The goal of my project is to understand how SOCE regulates Ca2+ signaling in dendritic spines and how LTP and downstream cascade of signaling is driven by Orai1. My preliminary results show that Orai1 plays a significant role in synaptic signaling, AMPA receptor recycling, and plasticity including maturation of maintenance of mature dendritic spines. Our in-vivo studies show that loss of ORAI1 inhibits LTP and causes significant impairment of working memory and learning in mice. Understanding the role of SOCE in synaptic plasticity will further our understanding of pathways of learning and memory and will help to design pharmacological agents for neurological diseases.

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