‘‘We can wipe an entire culture’’: Fears and promises of DNA biobanking among Native Americans

This paper explores Native American perceptions on DNA biobanking. A qualitative study was conducted among self-declared Native Americans living off reservation in two Midwest cities. Findings demonstrate a paradox: Informants maintain strong hopes for the transformative power of gene-based research while voicing very particular social anxieties. Emerging genomic technologies elicit concerns over the potential for genetic stigmatization or discrimination based on race, preventing access to health insurance or employment. Frequently, social anxieties adopt the narrative form of conspiracy theories which portray powerful agents exploiting or abusing a disenfranchised population. We argue that while Native Americans do not have a monopoly on the production of conspiracy narratives, their anxieties originate in a unique set of historical and social circumstances that position genetics research as part of a much larger political narrative. We conclude by suggesting that tribal approaches to biomedical research and in particular the use of biobanks that use concepts such as ‘‘DNA on loan’’ and emphasize trust building, collaboration and benefit sharing present a good model to deal with some of the anxieties elicited in this research but could also be taken as a model for biobank governance in general

Time-resolved single-cell RNA-seq using metabolic RNA labelling

Single-cell RNA sequencing offers snapshots of whole transcriptomes but obscures the temporal RNA dynamics. Here we present single-cell metabolically labeled new RNA tagging sequencing (scNT-seq), a method for massively parallel analysis of newly transcribed and pre-existing mRNAs from the same cell. This droplet microfluidics-based method enables high-throughput chemical conversion on barcoded beads, efficiently marking newly transcribed mRNAs with T-to-C substitutions. Using scNT-seq, we jointly profiled new and old transcriptomes in ~55,000 single cells. These data revealed time-resolved transcription factor activities and cell-state trajectories at the single-cell level in response to neuronal activation. We further determined rates of RNA biogenesis and decay to uncover RNA regulatory strategies during stepwise conversion between pluripotent and rare totipotent two-cell embryo (2C)-like stem cell states. Finally, integrating scNT-seq with genetic perturbation identifies DNA methylcytosine dioxygenase as an epigenetic barrier into the 2C-like cell state. Time-resolved single-cell transcriptomic analysis thus opens new lines of inquiry regarding cell-type-specific RNA regulatory mechanisms

Listening in on difficult conversations: an observational, multi-center investigation of real-time conversations in medical oncology

BACKGROUND: The quality of communication in medical care has been shown to influence health outcomes. Cancer patients, a highly diverse population, communicate with their clinical care team in diverse ways over the course of their care trajectory. Whether that communication happens and how effective it is may relate to a variety of factors including the type of cancer and the patient’s position on the cancer care continuum. Yet, many of the routine needs of cancer patients after initial cancer treatment are often not addressed adequately. Our goal is to identify areas of strength and areas for improvement in cancer communication by investigating real-time cancer consultations in a cross section of patient-clinician interactions at diverse study sites. METHODS/DESIGN: In this paper we describe the rationale and approach for an ongoing observational study involving three institutions that will utilize quantitative and qualitative methods and employ a short-term longitudinal, prospective follow-up component to investigate decision-making, key topics, and clinician-patient-companion communication dynamics in clinical oncology. DISCUSSION: Through a comprehensive, real-time approach, we hope to provide the fundamental groundwork from which to promote improved patient-centered communication in cancer care

‘‘We can wipe an entire culture’’: Fears and promises of DNA biobanking among Native Americans

This paper explores Native American perceptions on DNA biobanking. A qualitative study was conducted among self-declared Native Americans living off reservation in two Midwest cities. Findings demonstrate a paradox: Informants maintain strong hopes for the transformative power of gene-based research while voicing very particular social anxieties. Emerging genomic technologies elicit concerns over the potential for genetic stigmatization or discrimination based on race, preventing access to health insurance or employment. Frequently, social anxieties adopt the narrative form of conspiracy theories which portray powerful agents exploiting or abusing a disenfranchised population. We argue that while Native Americans do not have a monopoly on the production of conspiracy narratives, their anxieties originate in a unique set of historical and social circumstances that position genetics research as part of a much larger political narrative. We conclude by suggesting that tribal approaches to biomedical research and in particular the use of biobanks that use concepts such as ‘‘DNA on loan’’ and emphasize trust building, collaboration and benefit sharing present a good model to deal with some of the anxieties elicited in this research but could also be taken as a model for biobank governance in general

Control of stemness in CD8 T cell differentiation

Thesis (Ph.D.)--University of Washington, 2023T cell stemness enables continual generation of cytotoxic effector cells from a self-renewing pool of multipotent progenitors. After an acute infection, memory T cells persist for years in a quiescent state and upon rechallenge, rapidly reconstitute an entire expanded T cell response. In chronic infection and cancer, characterized by progression of functional cytotoxic T cells to dysfunctional exhausted cells, stem-like progenitors provide a continual source of cytotoxic cells to fuel a persistent response. In both cases, the system must balance the need for differentiation to generate effector cells and for protection of the stem cell population. Different immune challenges manifest over different time scales and with variable pathogenicity, and as such, the size and characteristics of the stem cell pool that forms vary across these different challenges with distinct signaling environments. While the molecular components that control these outcomes have been exhaustively characterized, the regulatory principles by which they act remain unclear. Thus, the goal of my thesis work has been to reveal these regulatory principles using reductionist approaches that measure T cell differentiation at the clonal level, over time, and with isolation and perturbation of distinct differentiating populations under defined signaling conditions. I first provide evidence for a stochastic epigenetic gene silencing mechanism that enables robust memory formation in acute infection. I then identify cell-state and signaling context-dependent regulators of T cell stemness using a targeted screening approach across multiple phases of T cell differentiation under chronic stimulation