Drake Jensen, MS Chemistry ’15, is the recipient of the SIUE 2015 Outstanding Thesis award. Titled “Functional Analysis of Calmodulin’s Calcium Dependent Inactivation of Orai1,” Jensen’s thesis research focused on the further understanding of calcium ions and their intracellular movement through the transmembrane calcium ion channel, Orai1.
The Outstanding Thesis Award recognizes and rewards a graduate student whose thesis has been selected by the Graduate Student Award Committee as outstanding among all those nominated during the previous academic year. The winner receives a monetary award and their thesis is forwarded by the University to the Midwestern Association of Graduate Schools Distinguished Master’s Thesis Award competition.
Essentially, Jensen’s research created a binding relationship between the calcium-binding protein, Calmodulin, and two Orai1 peptide sequences to deactivate calcium intake through the transmembrane calcium ion channel, thus preventing excessive levels of cellular calcium uptake.
“The results are especially remarkable because this new-found interaction appears to be vital for cells to replenish cellular calcium depletion through a process called store-operated calcium entry,” said Jensen’s thesis advisor Chin-Chuan Wei, PhD, associate professor of biochemistry in the SIUE Department of Chemisry.
Several human diseases are directly associated with imbalances of intracellular calcium levels. Excess calcium uptake –also known as hypercalcaemia – is a leading cause of myocardial infarctions, relating Jensen’s results to health issues such as parathyroid functionality, tumor metastasis, kidney failure and severe combined immunodeficiency disease (SCID).
Through these findings, Jensen has not only impacted the physiological understanding of biochemistry but has also provided rich insight into further drug discovery in the area of immunology.
“Drake became the first researcher to show that signal changes in steady-state fluorescence do not always correlate with binding affinity– discrediting a common assumption in the field,” Wei said. “He was also the first to confirm the structural behavior of Calmodulin to Orai1 compounds in solution, setting new ground for what is now considered a rare binding mode for Calmodulin.
“While extensive research exists in the area of Orai1 channel activation, Drake is one of a few researchers to describe and propose plausible hypotheses for channel deactivation to halt intracellular calcium influx.”
Similarly, Leah O’Brien, PhD, professor and chair of the SIUE Department of Chemistry, said, “Drake was the first to separate the Orai1 complex into smaller domains so that various active portions of the channel could be identified.”
Jensen is currently a PhD candidate at the Washington University in St. Louis School of Medicine, studying biochemistry and molecular biophysics. He remains involved at SIUE, actively engaging in Wei’s research lab to train SIUE undergraduate and graduate students while also gathering data for projects outside the scope of his thesis work.