Graduate scholar Yuesong Hu (Salaita Group) has received a 2022 Predoctoral to Postdoctoral Fellow Transition (F99/K00) Award for the National Cancer Institute. The competitive award supports outstanding Ph.D. candidates as they complete their dissertation research training and transition in a timely manner to mentored, cancer-focused postdoctoral career development research positions.
In the F99 (pre-doctoral) phase, the award provides stipend, tuition and fees, and an institutional allowance. In the K00 (postdoctoral) phase, the award includes salary and fringe benefits, tuition and fees, research and career development support, and indirect costs.
Yuesong’s research at Emory has focused on developing methods to measure and elucidate the role of mechanical forces in immune response. “In the adaptive immune response, cytotoxic T lymphocyte (CTL) continuously “crawl” seeking evidence of foreign peptide fragments on the surface of other cells,” says Yuesong. “Once the T cell encounters a target cell with foreign or mutant peptides, then it is activated unleashing a potent immune response. Emerging evidence suggests that cell mechanical forces transmitted to the T cell receptor (TCR) contribute to its high specificity in antigen recognition and promote T-cell activation.” Understanding the immune response has important potential applications for cancer detection and treatment.
At Emory, Yuesong also designed a DNA-based microparticle tension sensor that allows for quantifying receptor forces in high throughput and also to measure forces at curved cell junctions. He used this assay to screen the dose-response function of drugs that modulate cell mechanics. “Because T cell responses are fine tuned by an array of co-receptors, I tested the role of mechanics in LFA-1 function,” explains Yuesong. “In this work, I demonstrated that the magnitude of LFA-1 integrin forces fine tunes TCR triggered activation and antigen discrimination. In addition, I revealed mechanically active LFA-1 defines the permissive zones for cytotoxic secretion, and suppression of LFA-1 forces significantly abrogates T-cell cytotoxicity.”
Yuesong’s award will fund further work investigating the mechano-communication between receptor forces, including the development of a DNA nano device to pattern ligands and investigate spatiotemporal colocalization of mechanical events. The device will be employed to test cell plasma membrane by engineering DNA on the surface of target cells. This will enable one to control and measure TCR-forces at authentic cell-cell junctions that mimic the chemical and physical properties of the immune synapse.