The University of Louisiana at Monroe

NSF Awards · FY 2026 · 2026-08

Most ice appears cloudy because tiny air bubbles form as water freezes. The bubbles that form during freezing can damage substances dissolved in the water. This project will focus on damage to substances such as proteins, pharmaceuticals, or vaccines. The project will experimentally control and quantify air bubble formation during freezing and study the impact of reducing air bubble formation on the stability of proteins. The results of this project will improve the shelf life of temperature-sensitive substances. For example, it will allow medicines that are thawed during shipping to be re-frozen without damage. Results of the project will benefit the biotechnology industry by improving resilience of the medical supply chain. Further benefits will accrue from training graduate and undergraduate students in research. The investigators will also conduct outreach at high schools on the interfacial science and engineering of familiar materials such as food, personal care products, or pharmaceuticals. This project will investigate the fundamental mechanisms of cryopreservation-induced damage in biologics. Protein denaturation is often believed to be attributable to denaturation at the ice-water interface. This project will instead focus on the role of gas-liquid interfaces formed in situ during the freezing process. The project will quantify the total air bubble-related stress across a variety of freezing conditions. A library of proteins with diverse surface activities and denaturation tendencies will be studied. Experiments will test the hypothesis that the benefit of deaeration is directly related to a protein's susceptibility to damage due to adsorption at the air-water interface. A key innovation will be the management of a strategic trade-off: introducing mild, controlled stress via deaeration to prevent significantly more destructive interfacial stress during subsequent ice formation. The overall aim is to lower the total burden of interfacial stress across the entire freeze-thaw cycle. If successful, this work will introduce deaeration as a novel third pillar of cryopreservation strategy, alongside the two well-known pillars of formulation optimization and freezing-rate optimization. The results will provide an alternative strategy for stabilizing biologics that are otherwise resistant to current protective methods. The project has potential benefit to biomanufacturing, biotechnology, and to facilitate storage and transport of heat-sensitive biomaterials. Additional benefits derive from training students at college and pre-college levels. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIH Research Projects · FY 2025 · 2024-05

Summary Endothelial barrier dysfunction (EBD) has been associated with crucial lung injury ((e.g. acute respiratory distress syndrome (ARDS)) and deaths in the Intensive Care Units. Approved medicine that specifically targets EBD does not exist, hence the development of efficient medical countermeasures in that context is of the utmost need. Synthetic somatostatin analogs (SSAs) suppress the secretion of growth hormone (GH), are FDA-approved, and are currently used in clinics for the treatment of acromegaly and neuroendocrine neoplasms. This R03 proposal is based on the concept that SSAs protect against EBD. If our hypothesis is proven correct, SSAs can be eventually tested against the corresponding disorders. Based on preliminary observations, we will pursue Specific Aim 1 to investigate the role of Lanreotide (LAN), Octreotide (OCT) and Pasireotide (PAS) in LPS- and IFNγ -induced EBD. To do so, we will utilize human lung microvascular endothelial cells, post-treated with SSAs after LPS or IFNγ exposure, to assess their effects in transcellular and paracellular permeability, cell injury and inflammation. Unfolded Protein Response (UPR) is a homeostatic signaling network activated upon increases of endoplasmic reticulum (ER) stress, and it is involved in the regulation of endothelial barrier function. Global UPR induction counteracts Kifunensine (UPR suppressor)-triggered EBD. Our preliminary observations suggest that LAN induces BiP-a UPR activation marker- and activates ATF6, which has been shown to deliver protection in experimental models of widespread disease. To further our studies, we selectively suppressed ATF6 in endothelial cells to reveal that targeted ATF6 suppression potentiates LPS-induced EBD. Based on our published and unpublished observations, we will assess Specific Aim 2, to examine the involvement of ATF6 in the protective effects of SSAs in EBD. We will test the effects of SSAs in inflamed endothelial cells that express more or less of ATF6, in the context of injury and barrier function. New preliminary data suggest that LAN and OCT oppose LPS- induced acute lung injury (ALI) in mice. Based on those observations, New Specific Aim 3 will further our knowledge on the effects of SSAs in a murine model of LPS-induced ALI, and in the context of ATF6. The completion of our studies will reveal a novel avenue of investigation, based on the SSAs application in disorders related to EBD. All necessary material is commercially available, and alternative approaches have been developed to cover most of the possible outcomes. To the best of our knowledge, thorough studies on the effects of SSAs in EBD - and in the context of ATF6 - have not been conducted, yet.