University of Vermont

Office of the Vice President for Research (OVPR)

2015-16 REACH Recipients

Congratulations to our 2015-16 REACH recipients! Please see their names and project descriptions below.

Yolanda Chen, Plant and Soil Sciences
How Do Insects Rapidly Evolve on the Pesticide Treadmill?

The "Pesticide Treadmill" describes a widely observed pattern where agricultural insect pests adapt to frequently used insecticides in conventional and organic cropping systems, and the emergence of resistant pests then forces the pesticide industry to develop novel insecticide chemistries.

Colorado potato beetle (CPB), Leptinotarsa decemlineata, is an exemplar of this phenomenon, having evolved resistance to 52 different insecticides and all the major classes of chemicals. How insect pests such as CPB are able to acquire the novel mutations that lead to insecticide resistance remains poorly understood. One possibility is that the insecticide itself may alter patterns of insect gene expression (DNA -> protein), and such patterning can be passed to subsequent generations, also known as an epigenetic effect. In insects, methyl groups (chemical formula: CH3) are used to silence genes to prevent transcription, or the coding of proteins. Sublethal doses of insecticides are known to remove methyl groups and allow transcription to occur. However, no previous studies have examined how epigenetics can contribute to the rapid evolution of insecticide resistance.

Here, we ask: 1) How does insecticide exposure influence patterns of methylation in CPB? And 2) How does insecticide exposure influence beetle gene expression in exposed and subsequent generations?

Nancy Gell, Rehabilitation and Movement Science
BeMobile: The Next Step to Wellness

In recent years the number of breast cancer survivors in the U.S. has increased substantially. However, breast cancer survivors often contend with adverse side effects associated with cancer treatment including fatigue, weakness, and decreased endurance. Adherence to physical activity recommendations minimizes these side effects and leads to improvements in physical functioning, quality of life, and self-rated health. Despite these benefits, physical activity participation rates by breast cancer survivors are significantly lower compared to the general population and other cancer survivors.

We propose to test BeMobile, an innovative and pragmatic intervention to support physical activity adherence among breast cancer survivors. BeMobile integrates known preferences and determinants of physical activity participation in women and breast cancer survivors including social support, professional guidance, goal setting, self-regulation, and environmental awareness. BeMobile takes advantage of low-cost but accessible technology such as text messaging, GPS, health coaching, and wearable physical activity sensors to engage breast cancer survivors in continued physical activity after completing oncology rehabilitation.

Through an iterative design, we will assess outcomes and incorporate participant feedback on the specific components to refine the intervention prior to a full trial.

David Kaminsky, Medicine
Ventilation Heterogeneity and Its Association with Lung Cancer

Lung cancer is the leading cause of cancer mortality in the United States. Recently, the U.S. Preventive Services Task Force recommended annual low-dose computed tomography (LDCT) for patients at high risk for lung cancer based on age and smoking history. LDCT has been shown to decrease cancer mortality by 20%. However, 96% of positive results are not cancer, leading to unnecessary workup and increase in health care cost. Utilization of a simple, non-invasive test that could identify a population of smokers at even higher risk of lung cancer would help better target LDCT screening and thus reduce the false positive rate.

Smoking is responsible for 85% of lung cancers, and is associated with structural changes that could alter the distribution of airflow and particle deposition throughout the lung, leading to an increased risk of lung cancer. We propose that the heterogeneity (unevenness) of ventilation in the lung is associated with lung cancer in patients who are current or former smokers. We will analyze ventilation heterogeneity locally in the region associated with the tumor on chest computerized tomography (CT) scan, as well as globally by means of specialized breathing tests in the lungs of patients with and without cancer.

Jennifer Laurent, Nursing
Food Addiction, High Fructose Corn Syrup, and Metabolic and Neural Correlates in Obese Children

Childhood obesity is epidemic. Seventy percent of obese children become obese adults with health conditions including diabetes, decreased quality of life, and mortality similar to tobacco users. Increasing attention has been given to the effects of obesogenic food environment on preoccupation and consumption of foods, particularly those high in inherently addictive added sugars. Food, food cues and anticipatory consumption of high-sugar foods activate neural reward pathwways assessed by MRI in obese adults. High fructose corn syrup (HFCS) is the most common source of refined sugar in sugar-sweetened beverages and other foods to enhance "flavor experience."Following HFCS consumption, obese children demonstrate more efficient absorption than lean controls.

This study examines the effects that HFCS and its metabolites have upon neural pathways and the relationship to food addictive behaviors in obese children.

Victor May, Neurological Sciences
Design, Synthesis, and Evaluation of Small Molecule Receptor Antagonists: A Cross-college Approach to Novel PTSD Therapeutics

Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) and its cognate G protein coupled PAC1 receptor (Adcyap2) participate in stress- and anxiety-related disorders including posttraumatic stress disorder (PTSD). Brain PACAP infusions increase anxiety-like behavior and, in agreement, PACAP null mice demonstrate decreased anxiety behaviors. Importantly, PACAP blood levels are elevated in female PTSD patients and PAC1 receptor polymorphism is associated with PTSD in a sex-independent behavior. Although the truncated PACAP6-38 peptide antagonist at the PAC1 receptor can ameliorate stress-related behaviors, no small molecule antagonist for the receptor has been identified to date.

Using recent crystal solutions for the related glucagen and corticotropin releasing hormone receptor, our laboratories in the Departments of Chemistry and Neurological Sciences plan to model the structure of the PAC1 receptor with the aim of defining the ligand binding domain for small molecule design, synthesis, and functional testing. The identification of parent small antagonists at the PAC1 receptor may present means for intervention and/or treatment of stress-related psychopathologies including PTSD.

Matthew Price, Psychology
An Information Systems Approach to Determine the Optimal Timing of Early Intervention to Prevent Post-Trauma Mental Illness

Approximately one in three victims of a traumatic event, including sexual assault and physical injury, will develop a chronic mental health disorder. Prevention of such conditions is possible by delivering intervention shortly after the event. Such interventions must be personalized to the needs of the patients in that they nust address underlying mechanisms, specific symptoms, and are delivered at the proper time. A comprehensive understanding of recovery during the acute post-trauma period is needed for such interventions to be delivered effectively.

The proposed study aims to use innovative methods to gather high-frequency data during the acute post-trauma period to determine the course of recovery using machine learning. The data will inform subsequent work to develop a personalized early intervention capable of preventing chronic mental health disorders.

Severin Schneebeli, Chemistry
Freeform Molecular Helices: Tiny Springs for Strong and Flexible Materials

Strong and flexible materials are needed as components of medical robots, artificial blood vessels and muscles, perfected body armor, etc. Advance in this research area requires molecular structures that combine flexibility in one dimension with rigidity in another. Inspired by macroscopic springs, we predict that freeform helices — i.e., helices with minimal interactions between consecutive turns — are very well suited for this task. We are inventing a unique approach for creating such structures with efficient chemical synthesis for the first time.

Our freeform helices, which cannot unfold, will likely be more stable than other natural and synthetic helices. On the contrary, DNA and proteins are flexible chains, which fold into helical structures due to relatively weak attractive forces. Unfolding can therefore take place readily in the currently known molecular helices, hindering the desired spring-like flexibility. Our freeform helices will likely surpass all of these shortcomings due to their unique shapes. In fact, we expect that even a relatively small electrical voltage can change the length of the helices by over a factor of three, providing the basis for artificial muscles and refined impact sensors and dampers.

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