Description:

Please join the Department of Pharmacology for a Works-in-Progress presentations

Nisha Shrestha, PhD
Postdoctoral Fellow in the Laboratory of Murali Prakriya, PhD

Structure-Function Analysis of the Intramolecular Clamp of STIM1
STIM1 is an ER localized Ca2+ sensing protein that communicates depletion of ER calcium stores to plasma-membrane localized Orai1 channels. At rest, the catalytic domain of STIM1, termed the CRAC activation Domain (CAD), is maintained in a quiescent state primarily via interactions with the first coiled-coil domain (CC1).  Upon store depletion, a series of conformational changes propagate from the luminal Ca2+ binding sites of STIM1 into its cytosolic domains, releasing CAD from CC1 and allowing it to bind and activate Orai1 channels. However, how CAD is embedded within the cytosolic domain of STIM1 to form an intramolecular clamp in resting conditions is not fully understood. In this study, we used alanine scanning mutagenesis to identify key residues that contribute to maintaining CAD in the resting state. My studies reveal new roles for a domain in STIM1 (CC2) that was previously not implicated in STIM1 activation and further reveals a potential molecular mechanism of the disease-linked R426C STIM1 mutation in CAD. Together, these studies provide a molecular understanding of the specific regions of CAD that are critical for maintenance of the intramolecular clamp in STIM1. 

Andrew Hoffman, PhD
Postdoctoral Fellow in the Laboratory of Huiping Liu, MD, PhD

Circulating Tumor Cells and Exosomes as Liquid Biopsy Biomarkers for Lung Cancer Patients
Understanding cancer progression and response to treatment is a key to providing better care for patients, ensuring that treatments are working and relapse is identified as quickly as possible. Liquid biopsies are a promising method of achieving these results, allowing for clinicians to evaluate patient response to therapy and monitor long-term prognosis in an easier and more cost-effective manner than through body scans. We have examined circulating tumor cells and circulating exosomes as liquid biopsy biomarkers for treatment response and metastasis risk, in this case particularly in patients undergoing immune checkpoint inhibitor therapy.