2022 Capitol Graduate Research Summit Presenters

Long-Term High-Fat/High-Sugar Diet Worsens Early Life Stress-Induced Obesity 

Exposure to stress early in life has been associated with adult-onset co-morbidities such as chronic pain, obesity, and metabolic disorders. We have established a mouse model of early life stress using neonatal maternal separation (NMS) that results in urogenital hypersensitivity and increased body weight compared to naïve (non-separated) mice. In this study we tested the hypothesis that consumption of a high fat/high sucrose (HFS) diet will worsen NMS-related outcomes. To examine this, pair-housed male and female naïve and NMS mice received either control or HFS diet beginning at 4-weeks of age. Weight gain, food intake, body composition, and pain-like behavior were monitored throughout the study. NMS mice on a HFS diet were found to have increased body weight and percent body fat compared to naïve mice on a HFS diet and to NMS mice on a control diet. Additionally, both NMS and the HFS diet resulted in significantly lower hind paw mechanical withdrawal thresholds indicative of hypersensitivity. After 20 weeks on their assigned diets, mice were given a glucose tolerance test. Both NMS and HFS diet consumption were found to result in impaired glucose homeostasis. Upon histological examination of the liver, HFS diet fed NMS mice were observed to have increased steatosis and hepatocyte ballooning. Our results suggest that HFS diet exacerbates the outcomes of NMS in both males and females, resulting in widespread sensitivity, weight gain, glucose intolerance, and steatosis. Future work will explore possible underlying mechanisms for the increased weight gain and sensitivity associated with stress and diet.

Tailoring Stem Cell Therapies to Enhance Regenerative Wound Healing

Incomplete wound closure results in chronic, non-healing wounds, which currently affects over 8.5 million people in the US every year, costing the healthcare system over $30 billion annually. With the aging population and rise in diabetes, the prevalence of chronic wounds is expected to rise. In diabetes, 15% of patients develop non-healing ulcers, with a greater than 50% recurrence rate. A recent retrospective analysis showed that Medicare cost alone for wound care was estimated to reach ~$97 billion, with diabetic wounds being the leading cause of non-traumatic lower-limb amputations. There remains a critical need for a therapy that can address this lack of wound closure and prevent the progression to complex chronic wounds that burden patients and our healthcare system. Adult Mesenchymal Stem Cells (MSCs) contain intrinsic regenerative properties and have been shown to enhance wound healing activity in diabetic wounds. MSCs can regenerate tissue by sensing and adapting to environmental changes within tissue, followed by secretion of regenerative factors that promote tissue regeneration. However, current research is limited due to the unnatural 2D expansion of MSCs on plastic, which results in loss of regenerative capabilities. My research demonstrates the ability to tailor regenerative factors released by MSCs in a 3D system that replicates the environment the cells see within native tissue. Within this system MSCs are exposed to stimuli that enhance their regenerative capacity. Ultimately, this research could lead to the development of novel tailorable therapeutics that lessen the economical burden of chronic wounds on the Kansas healthcare system.

Propel Project: Promoting Self-Determination and Social Engagement for Students with Autism

There are a growing number of students with autism entering secondary school, being served in general education classrooms, and in need of educational supports to enhance school and postschool outcomes. However, there is a dearth of evidence on comprehensive school-based interventions, particularly for students with autism served in general education classrooms. These students’ academic and social needs may be overlooked. This presentation will share findings from a multi-year project focused on goal setting and attainment through working with the Self-Determination Learning Model of Instruction (SDLMI) and how to utilize peer supports in inclusive general education settings. With support from trained teachers, students with autism in this first year of the project set and work toward goals in the core content subjects (e.g., English Language Arts, Social Studies) that will generalize to other topics and situations both in and beyond school settings. This project extends previous research on the SDLMI and PS by explicitly examining the impact of interventions on teacher and student outcomes in inclusive general education and special education settings. The overall purpose of the project is to evaluate the efficacy of interventions to promote self-determination and the use of peer supports in inclusive secondary core content classes to increase teacher knowledge and skills and enhanced student academic and transition outcomes. Identifying interventions that are effective for teachers and students has the potential to lead to enhanced outcomes for students, teachers, and schools within the United States.

Developing Effective Self Regulation Skills in Early Childhood

Self-regulation (SR) has long been studied as a significant predictor of children’s social-emotional development and cognitive development. Lack of maturation of SR skills has been associated with adverse behaviors, readiness, and academic success outcomes. Therefore, children who have difficulties in social interaction and emotional control show a lack of regulation of behaviors and early cognitive skills. This study aimed to review the research related to SR in early childhood. The research question used to guide this literature review: What are SR strategies that have been effective in children’s social emotional development and cognitive development? Preliminary findings indicate that the modeling of private speech, the use of objects to improve attention visually, and teaching mindfulness-based interventions are positively related to children’s cognitive abilities such as mental flexibility, inhibitory control, and working memory. Implications from this research are that educators should pay a greater focus on SR strategies at the early childhood level.

Sleep, Health and Burnout in Career Firefighters

Firefighters are at increased risk of sleep disorders, most commonly insomnia and obstructive sleep apnea (OSA). Sleep disorders are costly at the individual level in terms of mental and physical health, as well as increased workplace errors. Sleep disorders are also costly to organizations because of absenteeism and employee turnover. While previous research has found relationships between sleep, mental health, and occupational burnout, it is not clear how these associations evolve over time in career firefighters. Therefore, the goal of this study was to understand how insomnia and Obstructive Sleep Apnea (OSA) symptoms affected health and burnout in career firefighters. 117 participants filled out a survey assessing sleep disorder symptoms, as well as measures of perceived physical and mental health. Nine months later participants completed a follow-up survey that also included a measure of burnout. Nearly one third of participants were at risk for clinical insomnia, while nearly half were at high risk for OSA. Having more severe insomnia symptoms was associated with worse perceived mental and physical health both at baseline and at the follow-up survey. Furthermore, insomnia was a significant predictor of burnout at the follow-up survey. These data demonstrated that insomnia symptoms were associated with worse perceived health and burnout over time. Effective treatments are available both for insomnia and OSA symptoms, and this study suggests that providing support for sleep disorder screening and treatment as needed could improve overall health and prevent burnout in members of the fire service across the state of Kansas.

A Novel Technology to Treat Blood-Vessel Related Disease through Space and Time Synchronized Ultrasound and Laser

We have recently developed two novel technologies, namely photo-mediated ultrasound therapy (PUT) and ultrasound-assisted endovascular laser thrombolysis (USELT), which utilizes space-time synchronization of ultrasound and laser to induce bio-effects inside blood vessels. PUT can be used to treat medical conditions involving neo-vascularization such as diabetic retinopathy and macular degeneration, while USELT can be used to treat venous thromboembolism, which is the formation of blood clot in veins that can be fatal if the blood clot breaks loose and travels through blood stream to lungs. Existing treatment techniques like anti-coagulants and thrombolytic therapy are expensive, with treatment costs ranging from $15-20k and are often not very effective, resulting in a fatality rate of more than 11 percent (around 900 die each year in Kansas alone). We are developing USELT with an aim to provide effective treatment for venous thromboembolism, such that the overall fatality rate can be reduced, and lives can be saved. Diabetic retinopathy and macular degeneration are a major cause of blindness in US. Approximately 37,000 people suffer from diabetic retinopathy and 26,000 people from macular degeneration in Kansas. The existing treatment focused on frequent intravitreal injection of anti-VEGF is a huge burden on patients and physicians, and does not have long-term efficacy, with more than 50 percent of patients becoming partially or fully blind after 5 years. We are developing PUT with an aim to provide a non-invasive, cost-effective, long-term efficacy treatment to prevent blindness from macular degeneration and diabetic retinopathy.

Assembling Avengers “CAR T Cells” to eliminate Breast Cancer

Breast cancer is the most diagnosed cancer among females in the United States, as well as in Kansas. Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer accounting for 15-20% of all cases and having a critical survival rate of 12% in patients diagnosed with metastatic TNBC. Current treatment methods include surgery and chemotherapy, along with recently developed checkpoint inhibitors and targeted therapy. The current study evaluates the effect of Chimeric Antigen Receptor (CAR-T) cell therapy on TNBC. CAR-T cell therapy focuses on engineering the body’s own immune cells, the T cells, to better recognize tumor cells and eliminate them. We are developing CAR-T cells to target the TNBC tumor cells by simultaneously attacking dual antigens present on the tumor cells (i.e. EGFR and B7H3). For this study, CD4+ T cells were isolated from whole human blood and transduced with single CARs: EGFR & B7H3 and the Bispecific EGFR-B7H3 CAR. Tumor killing assay was performed by plating TNBC cell line MDA-MB-231 cells against the CAR-T cells for 96 hours. Tumor cell viability, total count and percentage dead were examined after 96 hours. As a result, we found significant killing of tumor cells with CAR-T cells compared to mock T cells in vitro. In vivo, EGFR CAR has successfully eliminated the tumors in brain metastatic model of TNBC in NSG mice and further experiments are ongoing. This therapy has been successful in treating hematological malignancies. The first patient to receive this therapy just completed 10 years of cancer free survival.

Soil Aggregates, Organic Matter, and Microbes: Improving Understanding of Processes that Support Soil Fertility and Function

Plants draw carbon dioxide out of the air and transform it into leaves, stems, roots, and other organic material. Much of this matter eventually mixes into the soil, where microbes convert most of it back into carbon dioxide. However, some of the plant material may linger in the soil for decades to millennia to form soil organic matter, or SOM. SOM provides vegetation with essential nutrients, increases the soil’s ability to retain water, and undergirds many other important soil functions. When soil is cultivated for agriculture, the amount of SOM contained within it tends to decrease, and many scientists expect this depletion to accelerate in coming decades. Crops planted in soils with low SOM tend to have lower yields and require greater amounts of costly fertilizers. Thus, developing land management practices that slow or reverse SOM loss is critical. To achieve this goal, we must understand the processes that control whether plant matter ultimately becomes SOM or if its carbon is transformed back into carbon dioxide. Most SOM is found inside of soil aggregates. These small clusters of mineral particles and other materials are the focus of our research, which explores 1) how the distribution of microbes, organic matter, and water within soil aggregates stabilizes SOM; 2) how the characteristics of a soil aggregate influence what microbial species associate with it; and 3) how the species makeup of microbial communities affects SOM accumulation. We hope our work will inform low-cost solutions to declining SOM stocks, benefiting Kansas farmers.