Young Innovators

University of Delaware assistant professors Emily Day and Jason Gleghorn have been named Young Innovators of Cellular and Molecular Bioengineering for 2018.

Both have articles featured in this month’s special issue of the journal Cellular and Molecular Bioengineering, which established the Young Innovators Award to highlight the research of outstanding assistant professors. Day and Gleghorn will also give invited talks in a session devoted to the award winners at the 2018 meeting of the Biomedical Engineering Society, to be held Oct. 17-23.

Each year, ten to 12 researchers internationally receive this award, and it’s unusual to have two recipients from the same university and department.

“The University of Delaware’s Department of Biomedical Engineering is full of talented researchers who are making major contributions to their fields,” said Dawn Elliott, department chair and Blue and Gold Professor of Biomedical Engineering. “I am so proud that not one, but two of our faculty members were identified as Young Innovators this year.”

Day is studying treatments designed to regulate the expression of the genes that drive cancer growth. Day’s paper in the special issue of Cellular and Molecular Bioengineering reports on the development of layer-by-layer assembled nanoshells as vehicles to deliver miRNA, gene-regulating material, into cells. She demonstrates that these nanoparticles can deliver the tumor suppressor miR-34a into triple-negative breast cancer cells, which subsequently reduces the expression of the cancer-promoting genes SIRT1 and Bcl-2. The result? Fewer cancer cells.

Day and her team coated negatively charged nanoshells with alternating layers of positive poly-l-lysine (PLL), a synthetic material, and negative miRNA. The outer layer of PLL protects the miRNA and helps it enter the cell. Day then used a variety of techniques to determine the particles’ ability to enter the target cells, inhibit expression of the desired genes, and reduce cell proliferation.

The nanoshells released about 30 percent of their miR-34a cargo over five days and suppressed SIRT1 and Bcl-2 by 46 percent and 35 percent, respectively. They also decreased cell proliferation by 33 percent. Future studies that build upon this foundational work to develop nanoparticles that maximize intracellular miRNA delivery could ultimately result in very potent and noninvasive treatments for cancer.

Gleghorn’s research centers on understanding how cells assemble into functional tissues to treat congenital birth defects and conditions associated with premature birth, maternal and fetal health, and pediatric diseases.

Gleghorn’s paper in this special issue reveals that TRPV4, an ion channel identified in other tissues in the human body, may regulate the development and formation of new blood vessels and airways of fetal lungs in utero.

His lab created an experimental model to culture embryonic mouse lungs and used time-lapse imaging to capture active changes in lung biology and visualize the organization of airway, smooth muscle, and blood vessel compartments.

Gleghorn found that TRPV4 expression was related to airway branching, smooth muscle differentiation, and lung growth. When TRPV4 was elevated, smooth muscle contractions doubled in frequency, and when TRPV4 was reduced, smooth muscle contractions reduced by 60 percent, demonstrating a functional role consistent with smooth muscle differentiation. Activation of TRPV4 increased the vascular capillary density around the distal airways, and inhibition resulted in a near complete loss of the vasculature.

Gleghorn concluded that TRPV4 could be a mechanosensor involved in transducing mechanical forces on the airways, leading to molecular and transcriptional events that regulate the development, growth, and formation of the three essential tissue compartments in the lung.

These new findings may uncover new therapeutic targets for the improved treatment of bronchopulmonary dysplasia, a chronic lung disease and the leading cause of mortality and morbidity in premature babies.