publications

Discomfort and dysfunction with swallowing solids can cause patients to skip medications. Here, I led the development of a liquid in situ-forming and tough (LIFT) hydrogel formulation capable of transitioning from a liquid to a solid once inside the stomach. In rodent and porcine models, we show that LIFT is able to form tough materials that protect and modulate the activity of small molecule, enzyme, and bacterial therapeutics in the stomach. 

LIFT confers many advantages due to its transitioning capacity, including the formation of a macroscale solid that (1) enables proximity of drug-modulating excipients with delicate drugs and (2) reduces the surface area-to-volume ratio compared to nanoscale and suspension formulations. These provide a mechanism of drug release and protection of sensitive therapeutics in the stomach.

Direct trainees who contributed to this manuscript are Matthew J. Pickett (co-author) and Georgia N. White (co-author). 

As co-author, I developed an inflammation-sensitive biomarker capable of integration into advanced sutures, which enables distal query of inflammation. These were nanoparticles functionalized with inflammatory protease-sensitive peptide linkers. When degraded in the presence of proteases, the nanoparticles release fluorophore biomarkers that can be detected in urine, enabling a minimally invasive way of monitoring inflammation in internal suture sites.

In this invited review, we examined the state-of-the-art in lipid nanoparticle technology for nucleic acid delivery to the endothelium, nucleic acid cargoes that have been investigated, and the translational challenges ahead. 

We sought to characterize the behavior of nanoparticles within the kidneys during normal and renal disease contexts, which may inform the design of targeted therapeutics in this space. Using anionic poly(ethylene glycol)-functionalized polystyrene nanoparticles as a model system, we observed that 20- and 100-nm, but not 200-nm, nanoparticles accumulated in renal vasculature, and that this effect was enhanced during a model of acute renal disease. 

Urine-derived renal progenitor cells (uRPCs) are attractive cell therapy candidates due to their capacity to repair renal disease and easy sourcing in human urine. Here, we sought to optimize non-viral gene delivery to these cells, which may confer advanced engineering and functionality to these cells. We examined polymer, culture, and gene cargo parameters to achieve robust gene delivery and editing in these primary human cells. 

Direct trainees who contributed to this manuscript are Soren L. Johnson (co-first author) and Ritika Jain (co-author).

We developed a triggered drug release mechanism for a novel renal disease drug, Bis-T-23, by exploiting its catechol groups. This chemical handle forms a reversible, acid-labile boronic ester linkage after interaction with boronic acid groups. We show that Bis-T-23 release is acid-triggered from boronic acid-containing polymers, and that the released drug is pharmacologically active in vitro after polymer uptake. This study could enable conditional release of drugs such as Bis-T-23 after endocytosis into target cells. 

A direct trainee who contributed to this manuscript is Ritika Jain (co-author).

We sought to characterize the behavior of model polymer drug carriers in the kidneys during normal and disease contexts, and focused on the effect of charge and size. By varying the monomer composition of polymers of fixed molecular weight (~25 kDa), we observed that highly anionic polymers accumulated more in the kidneys compared to other polymers. In a model of renal disease, we observed that renal disease impacted the distribution of highly anionic, 25-kDa, but not 47-kDa, polymers. This study provides insights into designing materials for renal-specific tropism. 

As co-author, I contributed to assays which characterize cell viability during and after optical tweezer manipulation.

We sought to develop next-generation sequencing methods to analyze phage display libraries, to identify new peptide motifs that bind to murine M2 macrophage. These cells are clinically interesting due to their involvement in tumor progression. We identified and validated new motifs by cloning in phage and testing binding in cultured cells. This workflow may be generalizable and aid in rapid discovery of new ligands in phage display campaigns. 

During my Ph.D., I characterized the integration efficiency of the Sleeping Beauty transposon system into a T-cell line after non-viral gene delivery.

During my Ph.D., I characterized the toxicity mechanisms of a hydrogel intended as a vehicle for cell delivery. 

As an NIH BESIP Research Intern, I contributed to the characterization of protein carbamylation in the kidneys by developing "pseudo-Western blots," which were Western blot representations of proteomics data.

As an undergraduate at UT Austin, I contributed to the development and characterization of PEG-based microparticles sensitive to enzyme-triggered degradation.