The tumor microenvironment (TME) exhibits several obstacles to immunotherapies including suppressive signals and a lack of costimulatory ligands. The TME causes T cell exhaustion and reprogramming of immune cells (e.g. macrophages) from an anti- to pro-tumor phenotype. Therapeutic approaches such as agonist CD40 monoclonal antibodies stimulate macrophages to induce anti-tumor programming. However, enthusiasm for monoclonal antibodies has been dampened by dose-limiting toxicities and inadequate pharmacokinetics. We are developing novel adoptive cell therapies by armoring tumor-targeted T cells with fusion proteins that provide costimulatory signals that are absent in the TME. Dual Costimulatory Receptors (DCR) are composed of the CD40L ectodomain combined with a costimulatory receptor endodomain. CD40L-DCRs are engineered into CD8 T cells to provide positive signals: CD40L interacts with TME macrophages, while simultaneously stimulating CD8 T cells via the costimulatory endodomain. I hypothesize that CD40L-DCR T cells are reprogramming macrophages from pro- to anti-tumor programming, providing greater therapeutic efficacy against tumors. Our in vivo studies showed improved survival using different CD40L-DCR candidates in a murine model of acute myeloid leukemia. In the CD40L DCR-T cell-treated mice, macrophages exhibited elevated levels of costimulatory molecules, suggesting an anti-tumor phenotype. To understand how CD40L-DCR T cells induce macrophage reprogramming, I am conducting in vitro experiments, co-culturing bone marrow-derived macrophages (BMDM), tumor cells, and CD40L-DCR T cells. I predict that CD40L-DCR T cells will induce BMDM to reprogram into an antitumor phenotype and increase phagocytosis of tumor cells. I will use IncuCyte and flow cytometry technologies to determine how BMDM programming is altered and how BMDM phagocytosis of tumor cells changes over time. These studies will support the translational potential of CD40L DCR-T cell therapy, opening doors to novel therapeutic interventions against a range of cancers.

There is a growing emphasis on providing "equitable" mental health care, and yet ‘equity’ is seldom defined clearly. Publicly-funded community mental health clinics’ (CMHCs) clinicians often serve clients from minoritized and underrepresented backgrounds, and thus may regularly observe and address equity issues, making their perspectives invaluable. This qualitative study explores CMHC clinicians’ perspectives of equity in their clinical practice. Our data was obtained from an online cognitive-behavioral therapy (CBT) training initiative in Washington State targeting CMHC clinicians serving youth. Participating clinicians (N = 245) received nine consultation sessions from CBT experts over a six-month period and completed pre-training and post-consultation surveys. In the pre-training survey, we asked clinicians to define equity and list resources they would want access to that can improve their consideration of equity in their practice. Descriptive statistics summarized clinician demographics. Using thematic analysis, clinicians’ open-ended responses were coded to identify emerging themes. Clinicians were predominantly female (74.7%), White (58.8%), had a master’s level training (90.2%), and a mean age of 34.2 years (SD = 9.3). After coding clinicians’ definitions of equity, ‘accommodation’ (i.e., tailoring services to clients) was the most endorsed theme (38.8%, n = 95), followed by ‘equality’ (i.e., treating clients the same; 19.6%, n = 48) and ‘fairness’ (i.e., treating clients with justness, 17.6%, n = 43). When asked about resources that could improve their considerations of equity, clinicians’ responses most frequently included diversity, equity, and inclusion (DEI) trainings, expanding reach to more diverse populations, equity-focused supervision, and financial aid (e.g., gas cards, food pantry). While CMHC clinicians’ perceptions of equity included common themes, their understanding may at times conflate equity and equality. These findings highlight the importance of increasing access to DEI-focused trainings and supervision along with other resources to assist CMHC clinicians in delivering equitable care.

Burnout is high among community mental health providers (CMHPs) and is important to remediate due to its associations with poor provider well-being and worse quality care. CMHPs’ clinical supervisors are well-positioned to address burnout, though little is known about whether supervisors implement burnout strategies that are perceived to be helpful by CMHPs. Thus, the purpose of this project is to investigate at what rates strategies identified as helpful by CMHPs are currently used by supervisors. Given the exploratory nature of this project, there were no a priori hypotheses. This mixed-methods study was conducted as part of an ongoing Washington state-funded evidence-based treatment (EBT) initiative called CBT+ which trains CMHPs serving youths in cognitive behavioral therapy (CBT) for depression, anxiety, trauma and behavior disorders (Dorsey et al., 2016). Participants (N=197) were CMHPs that participated in the 2022-2023 CBT+ training cohort and were predominantly masters-level, White, and identified as women. CMHPs were asked in a survey “How could your supervisor or agency help reduce your burnout?” and indicated whether or not (yes/no) each strategy was currently used by their supervisor/agency. Burnout solutions were coded inductively using thematic analysis by two independent coders who met weekly to resolve discrepancies. Chi-square goodness of fit tests and confidence intervals were used to examine and compare the rates of use for the solutions endorsed by at least 10% of CMHPs: Time off (endorsed by 26.9%), General self-care (16.2%), Supervision sessions (12.7%), Flexible work arrangement (12.2%), Check-ins (12.2%), Manageable caseload (11.2%), Morale/team building (11.2%), and Engaged supervisor (10.7%). Study findings can help mental health agencies and supervisors focus efforts on ways to implement strategies that are less often used to reduce CMHP burnout, and ultimately increase the quality of mental health care for youths.

One of the current challenges with evidence based practices (EBP) is addressing social risk factors (SRF) in conjunction with mental health therapies. SRFs are adverse social conditions which impact the physical and mental health of an individual, group, or community. Addressing SRFs in low-resource settings increases access to and engagement in EBPs by reducing immediate threats presented by SRFs. Training in EBPs does not typically include how to address SRFs. To understand possible ways to address SRFs in EBPs, we examine whether counselors delivering EBPs in a low-to-middle income country are addressing SRFs and how the strategies impact the implementation and delivery of an EBP. This study builds on the parent study, “The Building and Sustaining Interventions for Children (BASIC)”, which examines the implementation and sustainment of an adapted version of Trauma-Focused Cognitive Behavioral Therapy, called Pamoja Tunaweza (PT) implemented by lay counselors in Kenya.To examine strategies used to address SRFs in PT, twelve PT counselors from the BASIC study participated in semi-structured interviews with trained interviewers. We conducted an inductive thematic analysis to identify codes and themes derived directly from the interview data. We identified and organized segments of the interviews into codes which were further categorized into themes. Themes include types of strategies counselors used to address SRFs as well as their impact within the context of PT. We report the frequencies of the codes and themes as they relate to their impact. Preliminary results indicate that when counselors reported using strategies to address SRFs, such as referring guardians to resources and collaborating with school administration, counselors saw increases in child self-esteem and PT attendance. Understanding how addressing SRFs impact mental health and implementation outcomes can help inform training of counselors to effectively improve use and engagement of PT and other EBPs.

Burnout presents a significant challenge for mental health clinicians, affecting not only their well-being and turnover rate but also the quality of care provided to clients. Moreover, studies have shown that clinicians working in community settings face more burnout compared to those in private practice. Among the factors that have been implicated in clinicians’ burnout are the level of education, limited experience and training opportunities, individual variables, and demographic factors. In this study, I examined how clinicians’ reported competencies in core cognitive behavioral therapy (CBT) skills for treating anxiety, depression, trauma, and behavioral concerns are associated with their experiences of burnout. I further evaluated whether the relationship between competencies in core CBT+ skills and experiences of burnout is moderated by CBT+ training. The study draws on a diverse sample of 200+ community mental health clinicians who took part in Washington State’s CBT+ training initiative. I employed t-test and multiple regression models to analyze the data. Based on these analyses, there are anticipated insights of uncovering clinician experiences in how clinicians’ level of CBT skills and professional training experiences intersect with burnout. Findings are expected to inform targeted interventions aimed at reducing burnout and enhancing clinician retention across the workforce.