Category: Notable Grants

Healthcare worker (HCW) workload is a modifiable factor with strong relationships to both HCW well-being and patient safety. Team-based care is the gold standard for the treatment of critically ill patients in the intensive care unit (ICU). The robust body of evidence suggests that high workloads in the ICU are significant drivers of medication errors and HCW burn-out. While ICU physicians and nurses have developed workload standards in siloed efforts to create safe conditions, these analyses have omitted the interprofessional ICU team that includes critical care pharmacists, dietitians, respiratory therapists, advanced practice providers, and occupational/physical therapists. To date, no workload studies have evaluated the interdependent nature of the ICU team. Moreover, most workload metrics that hospital administrators use to make decisions do not reflect how work is actually conducted at the ICU bedside. We will build a workload visualization tool (Data-dRiven ICU Volume intErvention [DRIVE] dashboard) that will continuously analyze EHR data to provide multi-layered, time-tracking summaries that connect patient-level data to workload for the ICU team (Aim 1). The goal of DRIVE is to serve as a quantitative display of ICU team workload with metrics that directly reflect HCW and patient safety. In Aim 2, we will test a data-driven workload implementation framework (ICU Professional Resource Optimization [ICU-PRO]). In the ICU-PRO use case, we will assess the impact of a critical care pharmacist workload optimization intervention on medication errors and HCW safety. The rationale for this work is the results of the Optimizing Team Integration of Critical Care Pharmacists (OPTIM) study, which included >30,000 ICU patients from 64 centers that found that a high patient care workload for pharmacists was independently associated with increased mortality and length of stay, even after adjusting for relevant confounders such as disease severity and nurse ratio. Moreover, this study was the first to link a single healthcare profession workload (i.e., pharmacy) to patient outcomes in the context of the entire ICU team. The long-term goal is to improve safety and quality through optimization of ICU team workload. The central hypothesis is that optimized workloads are associated with improved HCW and patient safety. This innovative approach will explore previously undefined relationships for ICU workload and patient outcomes.

Funder: Society of Critical Care Medicine

Amount: $100,000

PI: Susan Smith, College of Pharmacy

The goal of this proposal is to invest in the capacity and infrastructure of the Southeast Coastal Ocean Observing Regional Association (SECOORA) glider observatory to develop, test, and implement autonomous passive acoustic monitoring of North Atlantic right whales in the South Atlantic Bight (SAB). Critically endangered North Atlantic right whales experience high mortality rates due to ship strikes and entanglement in fishing gear. These anthropogenic mortalities occur across the right whale habitat, including the northern foraging grounds, the Mid-Atlantic Bight migratory corridor, and the Southeast US calving ground off the coasts of South Carolina, Georgia, and Florida. A significant Unexpected Mortality Event beginning in 2017 has motivated the use of dynamic right whale management, a strategy that changes management based on near-real time visual and/or acoustic monitoring. Despite the expansion of passive acoustic monitoring efforts and studies on the efficacy of this approach in right whales’ northern foraging grounds, acoustic monitoring is much more limited in the Mid-Atlantic migration corridor and the Southeast US calving ground. Methods developed in the deeper waters of the foraging grounds may not be appropriate for use in the very shallow waters of the Southeast US calving ground. The proposed work would include the purchase of a passive acoustic monitoring science bay for use in a SECOORA glider, and four right whale monitoring missions on the Southeast US shelf during winter calving seasons. This project builds on recent test deployments of autonomous underwater vehicles called gliders, outfitted with an integrated passive acoustic recording system and onboard analysis that permits identification of the vocalizations of several baleen whale species, including the endangered North Atlantic right whale, in near-real time. These observations and experiments will support and expand existing networks for right whale monitoring led by collaborators at NOAA and Woods Hole Oceanographic Institution. UGA’s Sidaway Institute of Oceanography (SkIO) The team will purchase a Teledyne Webb Slocum glider science bay equipped with passive acoustic monitoring instrumentation that can be integrated into the SECOORA and/or SkIO gliders. The glider would be equipped to measure conductivity, temperature, and depth. UGA’s SkIO and the University of South Carolina will conduct glider missions to monitor North Atlantic right whiles in the SAB for a total of at least four missions during winter calving seasons over the three-year project. The UGA SkIO team will lead glider operations, with assistance in deployment, recovery, and auxiliary data collection from the University of South Carolina team. The PIs will expand the impact of this work through engagement with SECOORA stakeholders and partners, and through communication designed to reach scientific and non-scientific audiences.

Funder: NOAA (in partnership with SE Coastal Ocean Observing Regional Association, SECOORA)

Amount: $185,000

PI: Catherine Edwards, Franklin College of Arts and Sciences, Department of Marine Sciences

The Urban Agriculture and Life Sciences Summer Institute will build the capacity of urban educators to recruit and retain the next generation of urban agriculturalists by increasing engagement, knowledge acquisition, and knowledge retention of students using culturally responsive practices. For this project, 36 middle and high school educators will be selected to participate in a summer institute to learn how to develop and implement culturally responsive ALS lessons through professional learning, field experiences, and mentorship. Additionally, 18 previously trained educators will receive additional training on transformative mentoring and serve as instructional design support for teachers during curriculum development and implementation. The goal for implementing culturally responsive curriculum is to encourage student identity expression, increase problem-solving skills, and strengthen career aspirations related to ALS in urban settings. The expected outcomes for this four-year project are: 1) Expand the Urban Agriculture and Life Sciences Academy (UALSA) community of educators to include teacher mentors who support the creation and advancement of high quality and culturally responsive instruction; 2) Develop culturally responsive lessons focused on food safety, nutrition, and health in the areas of animal science, food science, horticulture, agricultural business and finance, environmental science and natural resources, and agricultural technology; and 3) Pilot culturally responsive ALS lessons, make revisions, and upload completed lessons to an online repository. All participants will receive membership to UALSA’s virtual community of practice, culturally responsive ALS curriculum, and other CRP resources and support to advance the implementation of the curriculum in classrooms.

Funder: USDA NIFA

Amount: $500,000

PI: James Anderson, College of Agricultural and Environmental Sciences

The purpose of this co-operative agreement is to develop a two-pronged immunoprophylactic strategy for the prevention and control of highly pathogenic avian influenza (HPAI) in poultry. We aim to develop a rapid and cost-effective immunotherapeutic designed to protect highly susceptible young chicks and to be deployed during emergency outbreaks. In parallel, we will also develop a vectored vaccine capable of inducing durable immune responses. By combining a rapid-acting immunotherapeutic with a robust vectored vaccine, this project aims to establish a comprehensive strategy for the prevention, control, and emergency preparedness of HPAI. Objective 1 will focus on developing an avian adeno-associated virus (AAAV) vector, termed AVI-Bloc, that encodes broadly neutralizing anti-influenza virus antibody in different formats (IgY, IgA and scFv). These constructs will be evaluated for efficacy in chickens using both individual and mass administration, including oral, aerosol and gel-spray delivery. We will generate a packaging cell line for low-cost production of AVI-Bloc vectors. Objective 2 will focus on establishing a DIVA-compatible vaccine platform using Rispens strain of Marek’s disease virus to deliver H5N1 hemagglutinin (HA) and neuraminidase (NA) antigens. We will develop immune-complexed, and M-cell targeting MDV vectored vaccines and evaluate their immunogenicity in birds. In objective 3, the protective efficacy of AVI-Bloc immunotherapy will be rigorously tested in challenge studies, particularly its ability to protect highly susceptible young chicks and provide rapid protection during emergency outbreaks. The protective efficacy of MDV Rispens-based immune-complexed and M-cell targeting vaccine candidates will be evaluated in HPAI challenge studies. We will measure neutralizing antibody responses, durability of protection, and the effects of immune-complexed antigen and M-cell targeting on the immunogenicity and protective efficacy of vaccine candidates. Key deliverables include the AAAV-based immunotherapeutic, low-cost scalable packaging cell line, a bivalent vaccine for HPAI and Marek’s disease, innovative tools for immune-complexed and M-cell targeting vaccine design along with the protocols for developing these immunoprophylaxis tools. The primary beneficiaries will be small and large-scale poultry producers, animal health biologics manufacturers, research scientists, poultry veterinarians, and policymakers. The outcomes are expected to provide rapidly deployable and effective immunoprophylactic tools for strengthening HPAI outbreak preparedness.

Funder: USDA APHIS

Amount: $1,999,861

PI: Lok Joshi, College of Veterinary Medicine

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Despite technological advancements, the 5-year survival rate for advanced HNSCC has remained stagnant for the past three decades. The FDA has approved immune checkpoint inhibitors (ICIs), including pembrolizumab and nivolumab, for the treatment of recurrent and metastatic HNSCC. While immunotherapy can induce durable remissions, only 15–20% of patients respond to treatment. There is growing interest in combining ICIs with chemotherapy or radiotherapy to enhance therapeutic efficacy. However, this approach has faced significant setbacks in recent clinical trials. Emerging studies suggest that the lack of activated dendritic cells (DCs) in tumors is a major reason for immunotherapy failure. Therefore, developing therapeutic strategies that not only eliminate cancer cells but also release stimulatory factors to promote intratumoral DC maturation and migration holds great promise for enhancing tumor sensitivity to immunotherapy. Our goal is to develop a novel adjuvant nanotechnology based on 7-dehydrocholesterol (7DHC)- encapsulated synthetic low-density lipoproteins (7DHC-LDLs) to boost anti-tumor immunity when used in combination with ICIs. 7DHC, a cholesterol analog, exhibits the highest rate of free radical chain propagation among known lipid molecules. Our preliminary data demonstrate that 7DHC-LDLs, like natural LDLs, accumulate in tumors by binding to the LDL receptor, which is upregulated in HNSCC. In the presence of reactive oxygen species (ROS), 7DHC triggers and amplifies lipid peroxidation in cell membranes, leading to ferroptotic cell death. In addition, our data suggest that cancer cells killed by 7DHC release danger-associated molecular patterns (DAMPs) and pro-inflammatory cytokines, which activate DCs and enhance tumor-reactive T cell priming, even in immunologically “cold” tumors. In this project, we will evaluate the pharmacokinetics and biodistribution of 7DHC-LDLs in orthotopic HNSCC models. We will test whether the innate adjuvant effects of 7DHC-LDLs can be leveraged to enhance the efficacy of anti-PD-L1 checkpoint blockade. Finally, we will perform a comprehensive analysis of the tumor microenvironment to elucidate the impact of this combination therapy.

Funder: NIH

Amount: $3,072,426

PI: Jin Xie, Franklin College of Arts and Sciences, Department of Chemistry

Drugs that increase O-GlcNAc have been developed and proceeded into clinical trials. Notably, O-GlcNAc is found on neurodegeneration associated proteins, like tau and α-Syn, and has been shown to inhibit their amyloid aggregation and associated pathology in vitro and in mouse models. However, little is known concerning any differences in O-GlcNAc levels in PD versus healthy brain tissues or whether O-GlcNAc modified α-Syn is excluded from corresponding insoluble inclusions. This project will directly fill in this missing knowledge at the level of the proteome, α-Syn modification levels, and the individual sites of O-GlcNAc on α-Syn. If we find that O-GlcNAc levels on disease relevant proteins are altered and/or that O-GlcNAc is only associated with soluble α-Syn, this information will provide strong supporting evidence to enable data-driven targeting of OGA as a potential therapeutic strategy.

Funder: Michael J. Fox Foundation 

Amount: $638,256 

PI: Robert Wells, Franklin College of Arts and Sciences, Department of Biochemistry and Molecular Biology 

There is an urgent agricultural need for novel approaches to combat the billions of dollars lost annually to the devastating root-knot nematode, an obligate sedentary endoparasite and

global threat to food and fiber crop production. The focus of this project is to resolve the mystery of the root-knot nematode feeding tube, a unique nematode-produced structure that forms within the cytoplasm of plant root cells selectively transformed into giant-cells by the nematode to serve as a nutrient sink leading to successful parasitism. Feeding tubes produced by all species of root-knot nematodes are essential for efficient withdrawal of nutrients from the cytoplasm by the sedentary adult females which require intensive nourishment for several weeks during the production of hundreds of eggs. While the feeding tube has been described at the ultrastructural level, its composition and mechanism of assembly remain an enigma. A combination of immunohistochemistry, structural biology, and protein interaction studies coupled with host-delivered RNA interference is proposed to identify the nematode proteins involved in feeding tube formation and translate this knowledge to develop novel root-knot nematode resistance in crop plants. The composition of feeding tubes and the underlying mechanism of their assembly is currently unknown and presents a truly transformative opportunity for a deeper understanding of root-knot nematode parasitism. The underlying hypothesis is that once adult root-knot nematode females have established giant-cells they secrete one or more proteins through their stylet into these cells that self-assemble into a feeding tube essential for efficient nutrient uptake. A molecular and biochemical understanding of the mechanism of feeding tube formation will enable the development of innovative, broad-spectrum strategies for combating this destructive agricultural pathogen. This project will provide new insights into the molecular basis of feeding tube formation by root-knot nematodes, which in turn will provide critical insight into how these nematodes successfully parasitize a wide range of plant hosts to aid in the design of novel and broad resistance in crop plants. PI Mitchum will partner with the State Botanical Garden of Georgia for field trip adventures and summer camp activities to improve STEM education through hands-on activities that will bring awareness to the hidden enemies lurking below ground that impact our food supply.

Funder: USDA NIFA 

Amount: $800,000 

PI: Melissa Mitchum, College of Agricultural and Environmental Sciences 

The purpose of this cooperative agreement is to evaluate the antiviral therapeutic potential of tannins against highly pathogenic avian influenza (HPAI) as natural anti-viral supplements and immunomodulators in poultry. Tannins, plant-derived polyphenolic compounds and their metabolites, have highly effective antiviral effects against broad spectrums of pathogenic viruses including influenza virus H3N2, H5N3, herpes simplex virus-1, Newcastle disease virus and adenovirus1-5. Thus, the proposed studies will develop effective therapeutic strategies with natural antiviral bioactive compounds to prevent poultry from HPAI infection and strengthen poultry immune system, maintaining sustainable poultry production and U.S. food security. Activities include 1) Evaluating antiviral effects of tannins against HPAI in vitro to elucidate the anti-HPAI mechanisms (mode of action) of tannins; 2) Evaluating effects of tannins on immune modulation in chicken macrophage cells and/or chicken mesenchymal stem cells under HPAI infection conditions; 3) Optimizing tannin inclusion level for the efficient growth and immunoprotecting potential in laying hens and turkeys; 4) Evaluating anti-HPAI effects of tannins in HPAI virus challenge studies with laying hens and turkeys (BSL3). Deliverables are obtaining data on anti-HPAI effects of tannins, their antiviral mechanisms, immunoprotected effects of tannins, optimization of tannin inclusion, HPAI challenge data, performance, mortality, and publications.

Funder: USDA PHIS 

Amount: $1,716,819 

PI: Woo Kyun Kim, College of Agricultural and Environmental Sciences 

By integrating innovative biotechnology and a comprehensive understanding of viral-host interactions, this approach aims to significantly mitigate the threat of highly pathogenic avian influenza (HPAI) in poultry through oral prophylaxis. This agreement evaluates the potential of natural compounds, alone and in combination, as immunomodulators and antivirals against HPAI. We will test each compound and compound combination for their safety and mechanisms of action in vitro using different tissue culture systems. Follow up studies will optimize dosage and delivery routes (via feed or water) and assess their efficacy against HPAIV infection in laying hens. In addition, we will investigate the immune response stimulated by compounds, monitor viral evolution, and study the impact of interventions on the microbiome. Finally, compound combinations will be assessed in chickens for their synergistic effect and to establish improved regimens to promote animal health. Deliverables include compounds with proven effect in increased resistance to HPAIV, administration regimens for compound combinations, clinical, immunological, and histopathological data, viral evolution and microbiome analysis, scientific publications and other reports that will help advance licensing of the compounds for agricultural use. The project will validate interventions to increase resistance to HPAIV infection, mortality, and transmission in poultry, paving the way for targeted therapies that promote a healthy balance and resilience against infections. Hence, the project will benefit the US egg and poultry industries, representing a substantial investment in the future of both animal and human health, with the potential to yield transformative results that extend far beyond avian influenza.

Funder: USDA APHIS 

Amount: $1,789,340 

PI: Daniela de Souza Rajao, College of Veterinary Medicine 

Driven by the urgent need to safeguard the US poultry industry from the devastating impact of Highly Pathogenic Avian Influenza (HPAI), this project leverages a powerful synergy between the University of Georgia’s cutting-edge research capabilities and the established industrial expertise of CEVA Animal Health and BioStone Animal Health to deliver a transformative solution: the first US-approved, mass-vaccination-ready modified live virus (MLV) vaccine against HPAI, accompanied by a comprehensive suite of companion DIVA diagnostics. This involves generating an H5N2 MLV candidate that is stable, grows to high titers (≥10^6 TCID50/mL), and elicits protective immune responses against aggressive H5N1 HPAI challenge after a single dose. The H5N2 MLV will be designed with a chimeric segment and incorporate specific molecular markers with unique sequences. Molecular diagnostic tools, including real-time RT-qPCR and NA-based serological assays, will also be developed to differentiate infected from vaccinated animals (DIVA). Key deliverables include a US-approved, mass-vaccination-ready influenza MLV against HPAI, along with reports, peer-reviewed publications, and other documentation necessary for vaccine and diagnostic tool approvals. The expected outcome is a reduction in the impact of HPAI virus pathogenesis and transmission in commercial poultry premises, specifically layer and turkey operations. The successful vaccine will stimulate humoral, mucosal, and cellular immunity, offering more effective protection against diverse HPAI strains. This project will positively impact the broader US poultry industry by providing a valuable tool for controlling and preventing HPAI outbreaks. Sub-awardees, including CEVA Animal Health and BioStone Animal Health, play crucial roles. CEVA will contribute their expertise in generating the first licensed MLV against avian influenza for poultry use in the US. CEVA and BioStone will also develop nucleic acid-based and ELISA-based diagnostic assays, respectively, providing an all-in-one vaccine and differential diagnostics platform.

Funder: USDA APHIS 

Amount: $1,999,873 

PI: Daniel Perez, College of Veterinary Medicine