Publications

Recent research has documented the harmful health consequences of structural-level stigma that targets sexual and gender minority (SGM) individuals. In the case of sexual and gender minority youth (SGMY), life trajectories are shaped not only by targeted, SGM-focused policies, but also by social policies more broadly which may have unique impacts on SGMY given their social position. However, little work has explored the pathways that connect both targeted and universal social policies and the health and well-being of SGMY. In this study, we conducted 68 qualitative interviews with SGMY in New York City (n = 30) and community stakeholders across the US (n = 38) and used the constant comparative method to identify the pathways through which social policies affect SGMY health and well-being. We propose three pathways that are shaped by specific inter-related social policies in ways that contribute to health inequities among SGMY: 1) access to social inclusion in educational settings; 2) housing-related regulations and subsequent (in)stability; and 3) access to material resources through labor market participation. We also highlight ways that SGMY, and organizations that support them, engage in agency and resistance to promote inclusion and wellbeing. Drawing on ecosocial theory, we demonstrate how policies work across multiple domains and levels to influence cycles of vulnerability and risk for SGMY. We close by discussing the implications of our findings for future research and policy.

Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors with immunosuppressive microenvironments. To overcome suppression, we engineered circuits in which tumor-specific synNotch receptors locally induce production of the cytokine IL-2. These circuits potently enhance CAR T cell infiltration and clearance of immune-excluded tumors, without systemic toxicity. The most effective IL-2 induction circuit acts in an autocrine and T cell receptor (TCR)- or CAR-independent manner, bypassing suppression mechanisms including consumption of IL-2 or inhibition of TCR signaling. These engineered cells establish a foothold in the target tumors, with synthetic Notch-induced IL-2 production enabling initiation of CAR-mediated T cell expansion and cell killing. Thus, it is possible to reconstitute synthetic T cell circuits that activate the outputs ultimately required for an antitumor response, but in a manner that evades key points of tumor suppression.