The diagnosis of heart failure (HF) is based primarily upon clinical symptoms and, unlike many other disease entities, its relative incidence is increasing. Despite advances in terms of achieving early reperfusion following an acute coronary syndrome, myocardial injury still commonly occurs, giving rise to a cascade of adverse biological events that can culminate in a myocardial infarction (MI) and progressive left ventricular (LV) remodeling. This latter process, generically termed adverse post-MI remodeling, is a significant contributory factor to the development and progression of HF. One promising class of strategies to interrupt adverse post-MI remodeling entails localized, hydrogel-based delivery of bioactive molecules and stem cell derivatives. However, a lack of information on the fundamental mechanisms that govern therapeutic gain precludes optimization of materials and strategies for MI injections. The proposed project is focused on the biophysical component of this critical knowledge gap, with the goal of advancing design and delivery strategies for post-MI biomaterial injections. Our collaborative project integrates in-vivo studies on LV biomechanics following localized hydrogel injections in a porcine model of MI and a computational framework that can be used to efficiently evaluate and optimize MI injection strategies.

The species from Peromyscus species were recently established as model organism along with more traditional rodents, mice, and rats in the multiple areas of biomedical research.  One of the unique advantages of the Peromyscus is the parallel existence of multiple species in breed in captivity, that is utilized for comparative studies. However, lack of reliable transcriptomic data restricts the Peromyscus-based research. The proposed project is focused on the development of the full-length transcriptome de-novo assembly of P.leucopus and P.maniculatus with the goal to create a comparative map of tissue-specific transcripts and splice variants. Our collaborative work integrates the development of new molecular technologies for synthetic long reads accusation and computational pipeline for transcriptomes assembly, annotation, and comparative analysis.

Despite the many advances in diagnostic and surgical approaches to aortic aneurysmal (AA) disease, morbidity and mortality remain high. Unfortunately, AA surgical repairs are considered “high risk” and are therefore performed only when rupture is assured. Thus, a significant emotional and psychological burden is placed on those patients with small to mid-sized AAs who are left to “watch-and-wait” for AA growth to meet interventional criteria. To date, there are no effective strategies to attenuate AA progression in these cases. With collaborators at Clemson University, we are working to develop a nanoparticle based theranostic approach to diagnose and treat small-to-mid sized AAs by targeting only degraded elastin; a crucial extracellular matrix protein involved in the progression and failure of AAs. Through non-destructive ex vivo testing, the mechanical properties of aneurysmal tissue will be determined experimentally using a custom-designed mechanical testing device and state-of-the-art full-field digital image correlation (DIC). Likewise, the failure properties of these tissues will also be evaluated using burst pressurization and stretch-to-failure ring testing. The results of these tests will then be applied to finite element models to describe the complex stress-strain fields associated with the evolving AAs in vivo and then correlated with nanoparticle uptake via microCT. Collectively, these analyses will be used in developing a diagnostic tool to determine the rupture potential--that is, the ratio of mechanical stress to material strength-- and to evaluate the efficacy of our elastin-repairing treatment strategies for AA attenuation.

The aggregation of monomeric protein into filamentous structures, known as amyloid fibrils, has wide-reaching implications in disease, pharmaceutical processes, and nanostructure assembly.  Thus, modulating the aggregation process has applications in medicine, bioprocesses, and nanotechnology.  Nanoparticles have emerged as attractive tools for selective protein interactions as a result of their tunable size, shape, and surface properties.  Studies investigating nanoparticle modulation of amyloid protein aggregation have reported the effect of a myriad of nanoparticles upon aggregation propensity, confirming that both nanoparticle size and surface chemistry influence the ability of nanoparticles to influence amyloid protein aggregation.  However, the mechanism by which such influence is exerted remains largely unexplored.  The proposed project will couple experiments and molecular level theory to gain insight into the mechanism by which polymer coated nanospheres modulate aggregation of the amyloid-b protein, involved in Alzheimer’s disease.  Preliminary data, including the low stoichiometric ratio at which the influence upon aggregation is observed and the strong impact of surface charge and particle curvature, supports the hypothesis that nanoparticle-induced changes in the local solution environment drive their ability to influence amyloid protein aggregation.  Thus, investigations will focus on the development of molecular theory to describe changes in the local solutions environment and coupling theoretical predictions with experimental results.

Bacterial infections have evolved into one of the most urgent global health threats, leading to increased healthcare costs, destruction of local tissues, patient disability, morbidity, and even death. Facing the mounting crisis on the rise of antibiotic-resistant bacteria, it is essential to discover and design the next-generation portfolios of new antimicrobial agents. This effort requires a series of coordinated and cascade events for antimicrobial agents to attack bacteria. Nonspecific interactions are among the most promising approaches for evading antimicrobial resistance. Such interactions include Coulombic attraction between oppositely charged groups and hydrophobic-hydrophobic interactions. Due to the non-specific interactions, it would be more challenging for bacteria to develop mechanisms for resistance. We propose to design facial amphiphilic antimicrobial biomaterials containing multicyclic natural products. Our new design of macromolecular antimicrobials is demonstrated with novel cationic polymers containing a series of multicyclic natural products that are representatives of tri-, tetra- and penta-cyclic compounds. We will particularly probe interactions between cationic antimicrobial agents and bacterial membranes. We will carry out both experimental studies and computational modeling in parallel. The results could provide feedback to each other for improving the understanding of interactions at the molecular level. In experimental studies, we will prepare vesicles using model lipid compounds and further encapsulate dyes, which will be subject to antimicrobial agents. The leakage of dyes could indicate the binding strength of cationic agents with negatively charged vesicles. The theoretical modeling will expand on previous work on the binding of charged peptides to the plasma membrane of eukaryotic cells to model the interactions of charged facial amphiphilic molecules on the double membranes of Gram-negative bacteria.  We will start with reproducing some essential physics of these double membranes without the presence of the antimicrobial agents, and once we have a working code, we will begin to elucidate the synergistic coupling of interactions that are required to reproduce the experimental results.

• Fabrication, functionalization, and characterization of nanomaterials and diagnostic assays

• Analyze large sets of experimental dynamic process data using novel filtering and optimization techniques

• Automated identification of arterial calcification by utilizing machine learning strategies

• Elucidate the influences of electrokinetic parameters on biomolecules separation
• Advance designs and regimes of pulsed electrophoresis for small biomarker separation

• Gain mechanistic understanding of the membrane fusion event
• Design materials and/or therapies that enhance the immune response

• Process in-vivo cellular dynamics/ movement data in a mouse stem cell model
• Use extendable semi-flexible chain model to capture the mechanics of collagen networks

• Enhance understanding of transcription factor behavior during cerebrovascular cell stimulation
• Extend findings toward identification of a novel therapeutic target

•  Identify novel physiological mechanisms that modulate stem cell function and differentiation. 
• Provide a rational basis for designing stem cell technology

Participants will be educated on the utility and limitations of computational modeling in biomedical engineering. Students will build simple finite-element models that simulate blood flow through the coronary artery and the transport of a drug in the bloodstream.
(Research at the interface of experimental and computation)

In this hands-on workshop, participants will be introduced to basic programming skills in Python. Participants will also gain functional knowledge of manipulating, properly maintaining, and archiving Big Data. 
(Research at the interface of experimental and computation)

This program consists of a series of professional development workshops. Each one-hour session provides university-wide expertise, and an opportunity for participants to interact with a larger, more diverse group of undergraduate researchers. Topics include "Applying to  / Preparing for Graduate School",  "Effective Poster Presentation", "Research and Ethics", and "Resumes and Cover Letters". 
(Professional Development)

Participants will learn how innovations are translated to market and the commercialization activities associated with this process. Upon completion of the workshop, participants will receive a Certificate in Technology Innovation and Entrepreneurship Training.
(Research beyond discovery: Entrepreneurship and Commercialization)

Participants will be introduced to the concept of intellectual property and intellectual space as well as the basic process of a patent application. Students will study examples of patents held by University of South Carolina researchers, including REU mentors. 
(Research beyond discovery: Entrepreneurship and Commercialization)