Funded Pilot Projects- Rounds 2 & 3
AWARD RECIPIENTS- ROUND 2
Project title: Functional screening of inflammatory signals that create a supportive microenvironment in leukemia
Acute myeloid leukemia (AML) is one of the deadliest hematopoietic malignancies. The 5-year overall survival rate for patients has stagnated for the past 30 years at 25%, underscoring an urgent medical need for new and improved therapies. Genetic heterogeneity and secondary events leading to relapse complicate treatment with any one single agent in AML Despite the well-known critical roles that microenvironmental cytokines and cellular factors play in normal hematopoiesis, identification and targeting of the key functional elements of the AML microenvironment has been largely unexplored. In this proposal we are testing the hypothesis is that pro-inflammatory cytokines provide a growth advantage to leukemic cells by influencing the functions of T lymphocytes and by reprogramming stromal cells in the microenvironment. BUILD EXITO Alum Mona M. Hosseini is now a graduate student at OHSU. Mona had the opportunity to train summer interns and other research assistants in the lab, has published a first-author paper (Hosseini, M 2018, Leukemia) and has done multiple presentations, abstracts and oral. EXITO Alum Ruthey Viver has presented at internal retreats.
Jason L. Burkhead
Project title: Understanding the role of zinc in Wilson Disease
Wilson Disease is a rare inherited disorder that results in severe pathologic copper accumulation in the body and impacts an estimated 1:30,000 people. The disease is caused by mutations in the ATP7B copper transporter that leads to pathologic and ultimately lethal copper accumulation in tissues, particularly in the liver and brain. Though the genetic cause of Wilson Disease is known, the underlying mechanisms by which copper overload causes disease is still poorly defined. Copper accumulation is expected to induce oxidative damage to cellular structures; though this mechanism appears to be more apparent later in disease progression, while the early and copper-specific molecular effects of copper accumulation remain elusive. Therapies for Wilson Disease include consumption of a low-copper diet, treatment with de-coppering drugs, and zinc supplementation. Zinc supplementation is thought to limit copper absorption by a competition and buffering effect in the intestinal cells, whereby copper is eliminated through the natural turnover of the intestinal lining. Dr. Burkhead's lab is investigating how copper accumulation in a Wilson Disease mouse model impacts essential zinc systems including zinc-dependent cell machinery and how clinical therapies impact zinc-dependent systems. The results of their work have the potential to inform and improve treatment of Wilson Disease. EXITO Scholar, Hamide Tifeki, is testing the hypothesis that zinc supplementation in the Atp7b-/- mouse mitigates copper-induced changes in zinc handling gene expression.
Matthew G. Drake
Project title: Effects of airway inflammation on transient receptor potential vanilloid type-1 receptor (TRPV1) expression on airway nerves
Airway nerves play a key role in airway diseases such as asthma. Nerves control bronchoconstriction (narrowing of the airways) and trigger cough. In asthma, these responses are exaggerated, which contributes to worse asthma-related symptoms and reduced quality of life for patients. Eosinophils are an inflammatory cell common in the airways of many asthmatics. Previously, Dr. Drake's lab found eosinophils cluster along nerves and increase nerve length and branching in patients with severe asthma. These neuro-immune interactions are also associated with changes in neuronal receptors, such as TRPV1. Understanding how eosinophils mediate these changes is a central focus of Dr. Drake’s research, with the ultimate goal to discover new treatment options for patients with severe asthma.
In Dr. Drake’s lab, EXITO Scholar Karol Wai explored these interactions using advanced 3-dimensional confocal imaging techniques to quantify airway sensory nerves (branch points and length), protein expression, and eosinophilic inflammation in bronchial biopsies from patients with and without asthma. Karol successfully presented her work at OHSU Research Week, at the EXITO Scholars year end forum, and contributed key insights towards data that is in the process of publication. She was also awarded a McNair Scholarship, in part due to her outstanding productivity during her time with EXITO.
Project title: Development and biological assessment of densely loaded porous silicon contrast agents for x-ray computed tomography and magnetic resonance imaging
High-resolution molecular imaging has the potential to help usher in an age of personalized medicine. The major challenge that remains in the field of molecular imaging is the marrying of low detection limits with high spatial resolution. This low detection limit demand is achieved by positron emission tomography (PET), which has poor spatial resolution. By contrast, magnetic resonance imaging (MRI) has excellent spatial resolution, but high detection limits. By development of suitable paramagnetic contrast agents to overcome the detection limit demand, molecular imaging by MRI would become possible. Dr. Goforth's study proposes that encapsulation of a chemical shift transfer agent in a porous silicon nanoparticle (PSi NP) host to generate a chemical exchange saturation transfer (CEST) imaging agent that will meet both the detection limit and spatial resolution demands of molecular imaging. A positive impact of accomplishing the study aims is expected to be development of a CEST contrast agent with the requisite sensitivity and biological clearance properties to enable clinical molecular MR imaging, with associated positive impacts on human health.
Project title: The effect of family violence on caregiving at end-of-life.
In the last year of life, 57% of Medicare beneficiaries depend on their daughters’ unpaid care labor (UCL). End-of-life (EOL) UCL can cause significant physical and psychological harm to providers, especially women with histories of childhood maltreatment. Using feminist poststructuralist narrative methodology, we performed and analyzed dialogic interviews with 21 women who provided end-of-life (EOL) UCL to parents who maltreated them in childhood, and 15 healthcare professionals who serve EOL UCL providers. We found that EOL UCL represents a re-traumatization for many women, resulting in avoidable injury, illness, and complicated grief, and increasing vulnerability to future victimization. During EOL UCL, participants were subjected to isolation, domination, deprivation, betrayal, and identity assault mirroring their childhood traumas. In childhood and in EOL UCL, structures of power perpetuated patriarchal norms of family and femininity, constraining participants’ capacities for self-expression, self-esteem, and self-direction. Our analysis also uncovered factors which predicted or protected against gendered re-traumatization. The findings of this study will be presented at the Gerontological Society of America 2020 Conference, several other abstracts have been submitted, and three manuscripts being prepared. The knowledge gained will inform new policies and practices to create equity in care for persons with life-limiting illnesses and their families.
Project title: Exploring the experiences of students of color in field education: Building and sustaining a more diverse social work labor force
Expanding high-quality, culturally-competent behavioral health care research and services are critical components of efforts to reduce health disparities facing racial/ethnic minority communities (Cohen, Gabriel, & Terrell, 2002; NIGMS, 2011). The national projection that people of color will become the majority population in the US in the coming decades affirms the need for culturally-relevant mental health services (Cohen, Gabriel, & Terrell, 2002). Given that social workers constitute one of the largest groups of behavioral healthcare providers, it is essential to prepare social work students to provide effective services that are compatible with the needs, beliefs, and practices of diverse communities. Dr. Mehotra's project aims to better understand the experiences and needs of social work students of color in field education, a central component of professional training. Study findings will inform efforts to strengthen successful outcomes for students of color in social work field education in order to build and sustain a more diverse, culturally-competent pool of behavioral health care providers prepared to meet the needs of racial/ethnic minority communities.
Project title: Enhancing the aquaporin-0/Calmodulin membrane protein complex for high-resolution structure determination by single particle CryoEM
The aquaporins are a class of membrane channel proteins that form direct pathways for water permeation across the cell membrane that must be carefully regulated for homeostasis. The mis-regulation of water channel activity is associated with a range of pathophysiological conditions, including kidney disease, cataracts, brain oedema, diabetes and cancer. Dr. Reichow's research group is using methods in high-resolution single particle cryo-microscopy (CryoEM) to understand the detailed mechanisms of how water channel regulation in the eye lens is controlled by the calcium-signaling protein calmodulin, and how mis-regulation of this system manifests in formation of lens opacities, known as cataracts (the leading cause of blindness in the world).
Kimberly Dolan (EXITO Scholar, PSU Undergrad), continued research in the Reichow Lab (on a separate project), and her contribution has resulted in a co-first author publication that has just been accepted by Nature Communications. Kimberly graduated from PSU in 2019 and is now in a graduate research program at UC Berkeley. Jonathan Flores (EXITO Mentor, OHSU Graduate Student), continued to work with Kimberly Dolan on his thesis research project. He is the lead author on the same paper that was recently accepted (referenced below). Jonathan received an NIH Ruth L. Kirschstein Fellowship in 2019 and plans to complete his Ph.D. in 2021.
Flores JA†, Haddad BG†, Dolan KA†, Myers JB, Yoshioka CC, Copperman J, Zuckerman DM, Reichow SL*, Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9Å. Nature Communication. 2020 (accepted).
† - equal contribution
* - corresponding author
Project title: Evaluating the potential of ecoroofs as therapeutic landscapes
Hospitals are increasingly adopting therapeutic landscapes such as healing gardens, horticultural therapy gardens, and memory gardens. We identified over sixty hospitals nation-wide that have ecoroofs, or rooftop gardens. In order to explore the current and potential uses of these facilities, Dr. Starry and Co-PI Tina Burdsall led a team of undergraduate researchers that included EXITO alumni Arjun Viray and scholar MacKenzie Gray as well as PSU Honors students Rosemary Wood and Timothy Oxendahl in a mixed-methods research effort. Our study encompassed phone interviews of hospital ecoroof managers as well as analysis of national hospital databases. We also conducted behavioral observations on an ecoroof at OHSU. At this same location, in collaboration with colleagues at OHSU, we collected salivary cortisol samples from patients, staff, and caregivers who were waiting on the ecoroof or, as a control, indoors. We did not observe significant effects of time spent on hospital ecoroofs on stress as indicated by salivary cortisol. These findings may be explained by hospital visitor experience; behavioral observations demonstrated a wide array of different uses of the ecoroof space such as cell phone use and passing by. We identified two factors that significantly predict whether a hospital has an ecoroof: the number of Medicaid patients; and hospital type (non-profit, government, and privately owned). Qualitative analysis indicated that internal champions as well as external service providers can also increase the likelihood of hospital ecoroof installation. These findings have been presented at meetings of the Ecological Society of America as well as at a Green Roofs for Healthy Cities conference, and we have a manuscript in preparation.
Project title: How the heart of the red-eared slider turtle can continue to beat in the absence of oxygen
Project summary coming soon!
Project title: Effects of Virtual Companion Animals on Human Emotional Health
Dr. Swobodzinski's study was designed to examine whether experiences of companion animals provided by a virtual reality (VR) device induce greater positive psychological and physiological responses of individuals compared to less immersive technology and content. To that account, the study assessed emotional responses and sensations of "being there" of 285 individuals who were exposed to depictions of pet dogs via three different modalities (i.e., 360-degree video in VR, 360-degree video on a computer monitor, and images in a photo book) with or without additional sensory stimuli (i.e., sound and touch). Findings from the study inform future applications of VR devices in recreational and therapeutic settings that are geared towards improving quality of life and emotional health. A sizable number of undergraduate research assistants from PSU and Clark College, including EXITO Scholars and alumni, were contributing to Dr. Swobodzinski's study: Ridge Bynum, Xaaran Dolence, Jeanette Doorenbos, Nick Glover, Erin Grieschen, James Knight, Anastasiya Kozlovska, Alyssa Libak, Mary Macpherson, Hasan Mahmood, Rebecca Mudannayke, Cindy Nguyen, Vy-An Nguyen, Michael Nunnerley, Lacy Oviatt, Kira Rhodenhamel, Pista Szabo, and Amy Young. Drs. Swobodzinski and Mankowski (PSU), as well as Dr. Maruyama (Clark College), offered data collection training to the research assistants from both campuses joining together in a large and welcoming group environment that offered instruction, opportunities to ask questions and develop knowledge and skills in conducting research (e.g., research integrity oversight requirements; administration of experimental protocols; best practices for data collection; ethical conduction of research; data management skills). Select research assistants were also instructed on the use of participant scheduling software and were leading the recruitment, scheduling, and chaperoning of participants through the experimental data collection protocol.
AWARD RECIPIENTS- ROUND 3
Project title: Utility of airflow measures in predicting risk for aspiration in neurologic populations
The upper airway serves multi-functional purposes, including breathing, swallowing, and cough. Breathing-swallowing coordination (BSC) and the ability to cough are essential lung defenses. Impairment in the ability to swallow (dysphagia) is associated with increased medical costs and death. Dr. Britton's study examines the utility of cough-related and breathing-swallowing coordination (BSC) airflow measures in discriminating aspiration risk in individuals with and without bulbar and/or respiratory impairments due to amyotrophic lateral sclerosis (ALS). Preliminary evidence suggests that specific airflow measures of cough and BSC may detect risk for aspiration (entry of material into the airway during swallowing). However, the underlying nature of associations between these airflow measures and aspiration remains unknown. The information generated by this study will aid the development of cost-efficient methods for dysphagia assessment.
Project title: Exploring the role of virtual social support in health outcomes of HIV-infected men
HIV remains a serious problem in the United States, particularly for men who have sex with men (MSM). Studies show substantial benefit to reduce excess morbidity and mortality for people living with HIV (PLWH) who adhere to antiretroviral therapy (ART); however, it is estimated that only 19-25% of PLWH do so. Advancing targeted and innovative ART adherence interventions for HIV-positive MSM remains a high priority. Technology-based ART adherence intervention represents a novel approach to optimize ART adherence. However, a common problem with reporting on the effects of technology-delivered ART interventions is that most fail to “unpack” the intervention to gain a greater understanding of what factors were primarily responsible for behavior change. Dr. Sun will join an NIH R01-funded study team and focus her research training activities on unpacking the virtual social support component in a technology-delivered intervention through quantitative and qualitative methods. Dr. Sun's study is being conducted in concert with the parent study (NIH/NIDA R01DA039950; PI: Horvath) and will contribute to the scholarship in HIV treatment and prevention to reduce suffering from HIV that affect millions in the US and globally.
Project title: The resilience of microorganisms to fluctuations in energy sources
Microbial communities have a powerful influence on human health and disease. In biological systems, microorganisms are subject to dynamic shifts in resource availability, such as energy and nutrients, however, the mechanisms that govern microbial responses to such perturbations and the consequences to the biological system are not well understood. Dr. Thompson's project will examine the mechanisms that support resilience to perturbations in energy availability in a model cyanobacterium. We hypothesize that even closely related genotypes will vary in their resilience to perturbation and that single cells are tightly coordinated in their response to perturbation. Understanding the principles behind microbial resilience to perturbation will have profound implications towards improving our ability to predict and engineer microbial communities towards better human and ecosystem health.