The body’s immune system utilizes T cells to identify and kill tumor cells of growing cancers. However, hematological and solid tumors inhibit T cells by producing a tumor microenvironment (TME) that presents inhibitory and death signals that hinder the T cells cancer fighting potential. At Dr. Oda’s lab we work to overcome this TME obstacle by engineering exogenous proteins that can be expressed in T cells. These immunomodulatory fusion proteins (IFPs) combine an inhibitory ectodomain with a costimulatory endodomain. Therefore, when these novel T cells receive deadly messages from tumors, they instead interpret and rewire the signal in ways that increase their cancer combatting abilities. We have had success in engineering Fas-4-1BB and CD28/CD200R IFPs data supports the IFP’s ability to increase proliferation, metabolism, and antitumor properties along with decreasing exhaustion in T cells. This presentation will focus on our recent investigations into an IFP that modulates the relationship between SIRPa and CD47. It is known that tumor cells express CD47 which binds to SIRPa on macrophages and gives an anti-phagocytic “don’t eat me” signal. CD47 also binds to SIRPa on dendritic cells and shuts them down, effectively inhibiting an antigen presenting cell that is key in communicating cancer antigens to T cells for identification. By combining the SIRPa ectodomain with the costimulatory CD28 endodomain, we can manipulate this inhibition by CD47 which is overexpressed in TMEs. I use gateway cloning to prepare vectors for transfection. I transfect SIRPa/CD28 constructs into PlatE viral producing cells and transduce the virus into T cells for expression. From here, I set up serial killing over time assays to collect and analyze in vitro data. This research on IFPs can lead to improved clinical treatment for cancer patients, resulting in increased survival rates across a range of different cancers and patients of all ages.

Our immune system naturally fights cancer by using T cells to locate and infiltrate cancer cells. However, hematological and solid tumors counter this by presenting inhibitory and apoptosis-inducing ligands on their surfaces, effectively suppressing T cell activity. We address this barrier in cancer treatment with studies on genetically engineering T cells. Specifically, we are engineering T cells with a Fas-4-1-BB immunomodulatory fusion protein to overcome inhibitory signals and instead utilize them to enhance the T cells’ cancer-combatting abilities. Inhibitory signaling from Fas ligand (FasL) plays a major role in the proliferation and persistence of tumors in the body by protecting tumor cells from being attacked by lymphocytes. We are engineering T cells with an immunomodulatory fusion protein (IFP) that combines the Fas ectodomain on T cells with the pro-survival 4-1-BB signaling domain. This allows T cells to convert the inhibitory Fas signal from binding FasL that diminishes T cell activity to costimulatory 4-1-BB signal which upregulates T cell activation and survival. What we found is T cells transduced with the Fas-4-1BB IFP exhibit enhanced ability to proliferate and function in vitro. Fas-4-1BB T cells also exhibit metabolic changes that lead to increased spare respiratory capacity (SRC) and mitochondrial biogenesis. KPC pancreatic cancer and FBL leukemia models in mice show improved persistence and survival in T cells expressing the Fas-4-1BB IFP. In conclusion, our approach in T cell engineering with IFP allows for T cells to overcome deadly signals from tumors and interpret them as a pro-survival message, thus increasing T cell function in murine models. Our results suggest that such engineered T cells improves efficacy towards fighting both solid and hematological tumors.

Nationwide, many states are starting to provide training in evidence-based treatments for psychological disorders to clinicians from mental health organizations. In Washington state, many clinicians participate in a Cognitive Behavioral Therapy training (CBT+) each year, which employs a common elements approach to address multiple psychological disorders common in children. However, there has been limited research on clinicians’ underlying reasons for participating in these trainings. Thus, this study examines main motivations behind why clinicians participate in CBT+, along with whether or not differences in motivation exist amongst clinicians with varying levels of familiarities with CBT prior to training. In this study, surveys were distributed to CBT+ participants (N = 197) to self-report on a 5-point Likert scale their levels of agreement with each reason for participating in CBT+: organizational requirement, interest in learning/refreshing CBT skills, helping clients, and professional development.The participants also self-reported on their frequencies of using CBT prior to training, with answers ranging from “almost always” to “never”. For understanding clinicians’ motivations in general, I employed descriptive statistics. For evaluating potential differences in motivation amongst clinicians, I used four two-way ANOVAs, a statistical test employed to analyze differences amongst means, with post-hoc Tukey tests to compare the level of agreement for each reason for participation amongst clinicians with high frequency (n = 62), moderate frequency (n = 78) , and low frequency (n = 57) of using CBT. Ultimately, understanding clinicians’ motivations for participating in the CBT+ can help researchers tailor advertisements and refine features of training programs.These adaptations may engage clinicians in more effective ways by indicating how trainings can help them attain their specific goals. Future directions of research can investigate whether specific adaptations in response to clinicians’ motivations can enhance learning outcomes and feelings of satisfaction of clinicians.

Bias in healthcare is often hidden and expressed through unintentionally prejudiced communication between providers and patients. These “implicit biases'' often relate to a patient’s race, gender, or sexual orientation. Implicit biases are automatic attitudes and stereotypes that can operate outside personal awareness and lead to unequal treatment, health disparities, and a lack of patient support. Although much research focuses on implicit bias, the perspectives of those who experience it and the impact it has on these individuals is less explored. Of particular importance are voices of Black, Indigenous, and People of color (BIPOC) and those with marginalized gender identities or sexual orientations (LGBTQ+). These groups have historically suffered from health inequities. For example, research indicates that BIPOC people may be undertreated for pain and LGBTQ+ people may be refused care. The UnBIASED project at the University of Washington and the University of California, San Diego addresses implicit bias in patient-provider communication through computational sensing tools to provide communication feedback. Through 25 interviews with people who identified as BIPOC, LGBTQ+, or both, we explored patients' perspectives on experiencing implicit bias when communicating with healthcare providers. We analyzed interviews through an inductive qualitative approach to understand negative and positive experiences, and identify participants' ideal solutions for improving patient-provider communication. For example, participants suggested having a patient advocate, providing feedback to the provider, and improving providers’ cultural competence. We report on these findings with the goal of describing common pain points and specific sources of dissatisfaction among patients who experience implicit bias. These findings help raise awareness of clinical implicit bias from the perspectives of patients, encourage further research, and suggest patient-driven, patient-centered solutions for how implicit bias can be overcome at personal and institutional levels.

A great deal of research has focused on developing and testing evidence-based treatments (EBTs) for children’s mental health. Correspondingly, there has been a focus on improving the implementation of EBTs in community settings; however, current delivery rates of EBTs is largely unknown. Mental health providers across Washington are required to document EBT delivery with Service Encounter Reporting Instructions (SERI) codes, which are reported to the state Department of Behavioral Health and Recording. SERI codes may provide an avenue to understand delivery rates of EBTs across Washington, but existing data suggests SERI codes may be utilized infrequently or incorrectly. Data for this study come from an evaluation of the CBT Plus (CBT+) Initiative—a statewide, state-funded training in EBTs for childhood mental health problems. CBT+ provides training and expert consultation in Cognitive Behavioral Therapy (CBT) for anxiety and depression, Trauma-Focused Cognitive Behavioral Therapy (TF-CBT), and Parent Management Training (PMT). This study uses data from the 2019-2020 cycle of CBT+ trainings, and we will use descriptive statistics to characterize the frequency with which clinicians report using SERI codes. We will also examine clinician’s reports of if supervisors/senior leaders within their organization discussed the use of SERI codes. We predict the outcomes for clinicians EBP SERI code use will trend correspondingly to state reporting, although these findings are limited by the narrow dataset. We predict that SERI code use is positively correlated with discussion of SERI code use. Another limitation is the predominant use of self-report questionnaires after receiving CBT+ training. This research will give insight to support needed for more effective implementation of policies and reporting of EBP SERI codes. Billing code use is necessary to determine EBT penetration rates at a state level. By understanding the rates at which children in Washington receive EBTs, we can improve these treatments and outcomes.

Schools are an accessible setting in which to embed youth mental health care; however, anecdotal evidence indicates that caregivers may be less involved in treatment when it is school based. Previous literature examines the relationship between clinician embeddedness across different settings and the involvement of youths’ caregivers. However, it does not evaluate the quality of clinician’s contact with caregivers. This retrospective study aims to compare the frequency of clinician contact with youths’ caregivers across school versus non-school-based mental health care settings. I will extend the previous literature by evaluating the quality of clinician’s contact with caregivers (phone versus in-person). Data for this study came from a Washington State-funded cognitive-behavioral therapy (CBT+) training initiative in 2019-2020. All participants were clinicians (N=215) who attended an in-person training followed by six months of expert consultation, completed pre-training and post-consultation surveys, and received CBT+ certificates upon completion. In the surveys, participants reported demographic information, amount of school-based practice, and frequency of caregiver contact. I will conduct chi-squared tests to assess the associations between degree of school-based practice and frequency of interaction between clinicians and youths’ caregivers. I hypothesize that there will be less caregiver contact with school-based clinicians compared to non-school-based clinicians, and less caregiver contact with full-time school-based clinicians compared to part-time school-based clinicians. Next, I will use descriptive statistics to summarize the frequencies of phone versus in-person contacts between clinicians and caregivers. Findings from this study can better inform our understanding of clinician involvement with youths’ caregivers across different service settings, which could aid in efforts to improve the quality of mental health care delivered in schools.

Violence exposure during childhood has been associated with increased post-traumatic stress symptoms, negative physical health outcomes, and risk of future violence perpetration and victimization. Psychotherapy may help buffer against the negative consequences of violence exposure: however, little is known about how community-based clinicians address violence exposure in psychotherapy. Data for the present study came from CBT+ — a statewide, state-funded training initiative for child-focused community mental health clinicians in Washington State. As part of the training evaluation, CBT+ training participants completed a survey that assessed their comfort with addressing violence and aggression and the frequency with which they address these topics in therapy. Using data collected from this survey, we aimed to describe 1) clinicians’ comfort level in addressing issues of violence and aggression during therapy; and 2) the frequency with which clinicians address violence and aggression during therapy. Our results included descriptive data (mean, standard deviation, and range) on clinician’s comfort and frequency addressing violence and aggression, which indicated clinicians did not frequently address violence and aggression in therapy settings and did not have a high level of comfort addressing the topics . Understanding clinician’s comfort and frequency in addressing violence and aggression is an important step toward ensuring the CBT+ training is best meeting the needs of clinicians in preparing them to address these topics during therapy. Clinicians who are willing to openly discuss violence in therapy may benefit clients by helping to reduce the negative mental health effects associated with violence exposure. Findings can help inform future CBT+ trainings on addressing violence and aggression to improve clinician comfort and increase the frequency with which clinicians address violence and aggression.

The World Health Organization (WHO) defines social determinants of health (SDH) as “the conditions in which people are born, grow, live, work, and age”, all of which shape the conditions of daily life. There is significant evidence that those who have lower socioeconomic status’ and lower education are more likely to experience various mental health disorders (GAD, depression, etc.), and often do not have adequate services available to combat those disorders. Consequently, there has been increased attention to the importance of social determinants of health (socioeconomic status, living with racism, unstable housing) in relation to providing psychotherapies. We are looking to understand if prior to cognitive behavioral therapy (CBT)+ training, clinicians had received any training in social determinants of health, and if clinicians incorporate SDH into their delivery of CBT. Our descriptive analysis examines 195 licensed clinicians, and their answers to a variety of questions on their past training on social determinants. Based on past research, it is predicted that the majority of clinicians will have received some type of prior training on social determinants in relation to their delivery of CBT. Due to the importance of considering a variety of social determinants when conducting CBT, it is also predicted that clinicians often tailor their CBT to account for different SDH that their patients might be experiencing. This analysis will give organizations knowledge of what areas of training are being utilized by clinicians, therefore, giving them insight on what further trainings may be appropriate. This study may also help guide researchers when further studies surrounding CBT, and implementation are conducted.

Delivering psychotherapy via telehealth has become a necessity during the COVID-19 pandemic to ensure individuals with mental health problems continue to get access to evidence-based treatments (ESTs). Many clinical settings were unprepared for the transitioning from delivering therapy in-person into via telehealth, introducing many barriers for clinicians and patients. Several studies have found that telehealth can increase the accessibility of therapy and reduce costs associated with travel. Although telehealth has provided significant benefits, making it a potential long-term medium for delivering therapy, it has also posed several barriers that must be addressed for its use after the COVID-19 pandemic. In this study, we explored the barriers that clinicians experienced when transitioning from in-person therapy to telehealth. Data came from a Washington state-funded cognitive-behavioral therapy training initiative. Clinicians completed pre-training and post-consultation surveys. Survey questions covered a list of barriers that clinicians had to rank from a scale of 0 (not a barrier at all) to 10 (a very significant barrier). Barriers included technological problems to issues conducting clinical assessments. Descriptive statistics will be used to summarize clinicians’ responses. Clinicians may continue to use telehealth even beyond the pandemic and this may become the possible standard of care. In order to improve the delivery of ESTs via telehealth, we must understand clinicians’ barriers to using telehealth, and then identify ways to ensure using telehealth to deliver ESTs is feasible, acceptable, sustainable, and effective.