Rebekah Scheuerle is a senior in the chemical engineering department and has worked in the lab for 3 years. Rebekah has received the V.P. of Research Undergraduate Research Fellowship by The University of Texas at Austin (2012) for her research in the lab. She is interested in chemical and biological engineering and biotechnology. Her research interests include drug delivery, biomaterials, nanotechnology, microfluidics, diagnostics, and vaccines.
Rebekah is very active in student organizations on the UT campus. She has served two terms as president of the American Institute of Chemical Engineers (2011, 2012) and one term as press secretary (2010). In addition she served as chair of the Undergraduate Faculty Interview Committee (2012). Rebekah is also active in Omega Chi Epsilon, where she has served terms as secretary and service chair (2011,2012). In addition Rebekah is a member of Tau Beta Pi, in the Women in Engineering Program, and a Longhorn Band alum (2009,2010).
Rebekah is currently conducting research under the direction of William Liechty in the area of nanoscale hydrogels for oral delivery of siRNA.
The selectivity of small interfering RNAs (siRNAs) in silencing disease-causing genes through targeted degradation of corresponding messenger RNA is promising. Therapeutics in the form of siRNA could be powerful pharmaceutical tools, applicable to treatment of genetic disorders and cancers. Due to inherent instability, siRNA necessitate a delivery mechanism for protection from anatomical and physiological barriers. We hypothesize that nanoscale pH-responsive polymeric carriers are promising because they protect and allow for controlled, targeted release of siRNA. Uptake of these nanoparticles into endosomes, subsequent particle swelling, rupture of the endosome, and release of siRNA into the cytosol can result in gene knockdown of disease-causing sequences.
Through photoemulsion polymerization, we have synthesized, characterized, and optimized pH-responsive, selective, degradable, nanoscale hydrogel systems for delivery of siRNA. We have characterized the swelling, microenvironment, and effectiveness of these particles.
By increasing the hydrophobicity of the particles through manipulation of particle composition, we have decreased the critical swelling pH of the particles to match endosomal pH and characterized this behavior with dynamic light scattering studies. A degradable polymeric system is desired because it allows for more efficient release of therapeutic. It also allows the body to clear the particles, thus preventing internal polymer accumulation. Thus we have synthesized a degradable crosslinker and incorporated it into the particle composition, forming degradable particles. We have also characterized the microenvironment of the particles for a fundamental understanding of the impact of the polymeric network structure on membrane disruption. We have used pyrene fluorescence spectroscopy to study various polymer compositions because of its unique photophysical property dependence on microenvironment hydrophobicity. These studies supported observations that the hydrophobic polymer compositions result in increased membrane disruption. Through GAPDH silencing studies we have demonstrated effective gene knockdown using our pH-responsive hydrogel nanoparticles.
WB Liechty, RL Scheuerle and NA Peppas,
"UV-Initiated Free Radical Polymerization as a Robust Synthesis Method for pH-Responsive Nanoscale Hydrogels", Acta Biomaterialia (submitted).