Four College of Engineering research projects win CURC Awards

Thirteen students took home a total of four Celebrate Undergraduate Research and Creativity Awards, including Research: Highest Honors, Research: High Honors, Research: College Honors, and Research: High Honors.

Haley King, Katelyn Harada, Jeremy Valades, Jacob Bryant, and Daniel Vance
Award: Highest Honors
Title: Canine Exoskeleton for Mobility and Rehabilitation
Advisor: Anura Jayasumana

This project was aimed at developing an electronically controlled active exoskeleton that improves mobility and rehabilitation in partially paralyzed/weakened hind limbs of canines. This year's team developed a proof of concept system that uses microprocessor controlled stepper motors to emulate the hind limb movement of an exoskeleton for hind limbs . The control was based on the data gathered from a using sensors. Future work will include developing an autonomous skeleton.

The group consisted of 2 BioMedical/Mechanical Engineers Haley King and Daniel Vance, and 3 Electrical & Computer Engineers, Katelyn Harada, Jacob Bryant and Jeremy Valades. In addition to Dr. Jayasumana from the ECE department, they were also guided by Dr. Rebecca Packer, Dr. Nic Lambrechts, Dr. Dean Hendickson, and Sasha Foster of Veterinary Teaching Hospital, and Martin Kaufmann of Orthopets, an animal orthotics company.

Wahida Khan
Award: High Honors
Title: Identification of Poly-(C) Binding Protein Associated RNA Decay Factors
Advisor: Jeffrey Wilusz

Poly-(C) Bindings proteins (PCBPs) regulate various stages of gene expression including transcription, mRNA stabilization, and translational activation. Two PCBPs of interest are PCBP3 and PCBP4. Based on previous research, PCBP3 is highly expressed in induced pluripotent stem cells (iPSCs); however, it is barely detectable in human foreskin fibroblasts (HFFs). The converse is true of PCBP4; it is highly expressed in HFFs but barely detectable in (iPSCs). Therefore, the long-term goal is to investigate how robust changes in these PCBPs affect mRNA decay within differentiated cell lines (HFFs) and undifferentiated cell lines (iPSCs, and cancerous cells). The aim of this project is to identify additional mRNA decay factors that are directly associated with these PCBPs through protein-protein interactions. To address this problem, we created stable HeLa cell lines that express a FLAG-tagged PCBP of interest. The expression was confirmed with qPCR and Western blots of extracted mRNA and FLAG proteins from whole cell lysates. These FLAG-tagged proteins were extracted from whole cell lysates by co-immunoprecipitation with a FLAG-specific antibody. Proteomic mass spectrometry was used to identify associated proteins. These results were then confirmed with Western blotting.

Garrett Eppers
Award: College Honors
Title: The demonstration of a physiologically-based pharmacokinetic model to predict rifapentine and 25-desacetyl rifapentine disposition in humans
Advisor: Dr. Brad Reisfeld

Tuberculosis (TB) is an infectious disease caused by bacteria Mycobacterium tuberculosis. The bacteria usually attack the lungs, but TB bacteria can attack any part of the body such as the kidney, spine, and brain. Because TB continues to be one of the leading causes of death in many parts of the world, there are significant global efforts underway to identify drugs that are effective in combating this deadly disease. One such drug is rifapentine (RPT), which has the potential to shorten treatment duration and enhance completion rates compared with other rifamycin agents utilized in current anti-tuberculosis drug regimens.

Effective treatment for TB relies on the drug getting to the site of the bacterial infection in the lungs and other organs. Thus, for any given treatment regimen, it is critical to be able to estimate the amount of an anti-TB drug in relevant tissues over time. One extremely useful approach for this estimation is physiologically-based pharmacokinetic (PBPK) modeling, which employs a mathematical representation of relevant anatomical, physiological, and biochemical processes such that tissue-specific drug levels can be predicted for any specified dosing scenario.

In this study, a PBPK model for RPT was developed and validated for scaled up to humans. Using this model, predictions were made for RPT concentrations in the lung during various phases of TB treatment regimens, and these levels compared to those necessary to provide an antibiotic effect. These results suggested that current dosing regimens could be improved with respect to efficacy and safety. It is anticipated that this model will prove useful in evaluating and optimizing anti-TB treatments that utilize RPT, offering the opportunity to reduce treatment times and increase completion rates.

Ryan Rykhus, Jeffery Bennett, Megan Hamrick, Krista Henderson, Michaela Good, and Christine Sobolewski
Award: High Honors
Title: Small Molecule Inhibition of SMYD2
Advisor: Mark Brown

SMYD2 is an enzyme that is essential during human embryonic development. When it is aberrantly expressed in adults, it initiates tumorigenic cascades that lead to a wide range of cancers. The group of engineering students who won the CURC award used the coordinates that we resolved for the structure of the SMYD2 enzyme to engineer small molecules that bind to the enzyme and eliminate its catalytic function (thereby eliminating its ability to induce tumors). My research group has developed several successful cancer therapeutics in this way. These SMYD2 inhibitors represent our latest advance in the clinical management of cancer.

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