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NIH

Significance to VA: Lung cancer (LC) is the leading cause of cancer death for US veterans (USvets). Non-small cell LC (NSCLC) represents the majority of LCs with a poor 5-yr survival rate (~23%). NSCLC patients in the VA Health Care System are increasing as USvets often acquire tobacco addiction during military service fostering a large percentage of high-risk current & former smokers. The lung cancer incidence is also higher in USvets with lower survival rates, and LC is linked to service-connected exposure to carcinogens. Current treatment options for NSCLC are palliative, but have recently evolved with the use of immune checkpoint inhibitors (ICIs). Unfortunately, the effectiveness of ICIs in NSCLC remains modest with underlying resistance mechanisms elusive. Our research will define these resistance mechanisms and identify potential molecular targets & strategies to target both the NSCLC tumor & enhance ICI efficacy to produce a more durable outcome for USvets. Innovation & Impact: STK11 mutations (mtSTK11) are common in NSCLC and associated with resistance to immune checkpoint inhibitors (ICIs). Our data connected mtSTK11 to a novel dysregulation of caspase 9 (C9) alternative RNA splicing (ARS). Specifically, mtSTK11 NSCLC preferentially expressed C9b, which induces tumorigenesis, and a tumor immunosuppressive microenvironment (TIME) that supports ICI resistance. Genetic removal of C9b sensitized mtSTK11 NSCLC to ICI therapy in a NSCLC mouse model, thus highlighting the potential utility of modulating dysregulated ARS as a therapeutic. Human mtSTK11 NSCLC tumors also presented with the dysregulation of additional ARS events, which our data also support roles in NSCLC tumorigenesis & TIMEs. These data support the hypothesis that dysregulated ARS in mtSTK11 NSCLC modulates tumorigenesis and induces a TIME that promotes ICI resistance. Specific Aims (SAs): To interrogate our innovative hypothesis, we are proposing three specific aims: SA1: Determine the role of ARS events linked to the mtSTK11 oncogenotype in NSCLC tumorigenesis; SA2: Determine the role of specific STK11-regulated ARS events in ICI responses; & SA3: Determine the signaling mechanisms driving dysregulated ARS in mtSTK11 NSCLC. Methodologies: Unbiased “splicomic” analysis in human NSCLC will identify ARS events dysregulated in the mtSTK11 oncogenotype. Once validated for STK11/LKB1-regulation (e.g., by qRT-PCR), their roles in cancer biology will be determined using cells models (e.g., clonogenic potential) and mtSTK11 NSCLC mouse models (e.g., tumorigenesis & ICI resistance). The mechanism of action for specific ARS events will be determined by interrogation of the cell composition of the TIME using multiplex immunofluorescent histology & Aurora flow cytometry. State-of-the-art molecular manipulations (e.g., CRISPR), novel molecular “tools”, and complementary biophysical studies will be employed to modulate specific ARS events in our cellular & in vivo models and determine mechanistic function. Important ARS events and mechanisms will be interrogated in human NSCLC tumors for translational outcomes (e.g., survival, ICI resistance). Path to translation/implementation: Validation of our hypothesis would lead to the identification of new chemical entities (NCEs) that specifically block cancer-related ARS to foster a new generation of therapeutics for NSCLC. These NCEs would have limited toxic side effects: the “Achilles Heel” for some global ARS inhibitors. Additionally, our laboratory has shown that ceramide induction in NSCLC cells will reverse the dysregulated C9 ARS and sensitize cells to standard of care NSCLC treatments. A new ceramide-induction therapy, ceramide nanoliposomes, recently completed a phase I clinical trial (NCT02834611) for solid tumors (e.g., NSCLC) with an excellent safety profile. Thus, our proposed studies will build the molecular, mechanistic, & pre-clinical foundation for the development of new targeted ARS therapeutics and the clinical implementation of combination therapies using both ARS inhibitors & ceramide-induction therapy with ICIs in NSCLC to improve outcomes.

NCI - National Cancer Institute

PROJECT SUMMARY/ABSTRACT Squamous cell carcinoma (SCC) is one of the most common cancers worldwide, yet the early events that drive mutated epithelial stem cells toward malignancy remain poorly understood. While cellular plasticity has emerged as a key process enabling clinically normal mutation-harboring skin to acquire oncogenic potential and undergo malignant transformation, the non-genetic variables that regulate this process and ultimately drive tumorigenesis remain largely unknown. These gaps in knowledge can largely be attributed to a dearth of tools and models that capture pre-oncogenic stem cell identity landscape in intact tissues. In this project, I will investigate how the lymphatic vascular niche, increasingly recognized as a key regulator of epithelial stem cell, controls cancer stem cell fate transitions during early tumor initiation and malignant progression in skin SCC. Using deep imaging and sequencing approaches, we discovered that lymphatic vascular insufficiency predisposes stem cells to malignant transformation, while oncogenic plasticity propelling the transition from benign to metastatic carcinoma is preceded by dynamic lymphatic remodeling. The central hypothesis is that lymphatic niches evolve during tumor progression, initially supporting tolerance to oncogenic stress and later driving epigenetic rewiring that enables malignant transformation. Aim 1 will determine how lymphatic regression influences tolerance to oncogenic stress and promotes malignant transformation using in vivo lymphatic ablation models, chromatin accessibility profiling and organotypic culture systems. Aim 2 will define the molecular and spatial interactions between tumor-initiating cells and lymphatic niches during malignant progression. Leveraging enhancer-based proximity sensors, I will identify lymphatic-derived signals that promote stem cell plasticity potential. This work is expected to reveal context-dependent lymphatic cues that regulate early tumor initiation and malignant transition, while generating new tools to study vascular–stem cell interactions in vivo. These studies aim to uncover actionable pathways that can be targeted to intercept skin cancer before it becomes invasive, offering new opportunities for early intervention in a disease that affects millions. My training will take place in the Gur-Cohen Lab at UC San Diego and the Sanford Stem Cell Institute, a highly interdisciplinary environment with access to state-of-the-art tools in imaging, genomics, and computational biology. In this fellowship, I will gain advanced expertise in 3-dimensional tumor imaging, epigenomic analysis, and the development of experimental tools to interrogate the cancer stem cell interactome in real time. Under the guidance of a dedicated mentoring team, I will also strengthen my skills in scientific communication, grant writing, and mentorship. This integrated research and training plan will prepare me for an independent academic career focused on understanding how systemic signals influence stem cell fate and oncogenic potential.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary. In people living with HIV (PLWH) under antiretroviral therapy (ART), secondary lymphoid organs including lymph nodes harbor latent viral reservoirs, which are a major obstacle to curing acquired immunodeficiency syndrome (AIDS). While follicular helper T cells and follicular dendritic cells in B cell follicles are well studied as viral reservoirs in lymph nodes, recently it has been reported that lymph node CD4+ tissue-resident memory T (TRM) cells also serve as viral reservoirs in PLWH on ART. Our preliminary data demonstrate: 1) fibroblastic reticular cells (FRCs), a type of secondary lymphoid organ stromal cells, generate lymph node CD4+ TRM-like cells from peripheral blood CD4+ T cells; 2) FRC-induced lymph node CD4+ TRM-like cells support HIV-1 latency; and 3) FRCs maintain the survival of CD4+ T cells. However, the following critical aspects remain to be defined: 1) the extent of similarity between FRC-induced CD4+ TRM-like cells and bona fide lymph node CD4+ TRM cells, 2) the capability of FRC-induced CD4+ TRM-like cells to be HIV-1 reservoirs, and 3) the role of FRCs in maintenance of TRM viral reservoirs. Thus, the long-term goal of this project is to elucidate the roles of secondary lymphoid organ stromal cells in viral latency, which is critical to developing a curative strategy for AIDS. The objective of this proposal is to define how FRCs contribute to the generation and maintenance of viral reservoirs. Our central hypothesis is that FRCs facilitate the formation of lymph node CD4+ TRM cells that are highly permissive to HIV-1 latent infection and maintain the survival of latent viral reservoirs. The rationale of the proposed studies is that the completion of the studies will inform about the cellular and molecular mechanisms involved in both the establishment and maintenance of viral reservoirs, as well as possible means of a curative strategy. We plan to test our central hypothesis by pursuing the following three specific aims: In the first aim, we will use single-cell RNA sequencing, single-cell surface phenotyping and DNA sequencing that allows to determine the provirus sequence and phenotype of infected cells at a single-cell resolution, and an in vivo mouse model to establish that FRCs play a role in the generation of lymph node CD4+ TRM cells. In the second aim, to determine the molecular mechanism by which FRC-induced CD4+ TRM-like cells support latent infection, we will focus on a TRM- associated transcription factor and use chromatin immunoprecipitation and immunoprecipitation to define the interactions of the transcription factor with the HIV-1 LTR and host molecules in FRC-induced CD4+ TRM-like cells. In the third aim, we will employ the single-cell surface phenotyping and DNA sequencing that will be used to assess the ability of FRCs to maintain the survival of latently infected FRC-induced CD4+ TRM-like cells containing intact proviruses. This work is innovative because it combines a range of complementary approaches to test a novel hypothesis regarding the roles of FRCs in HIV-1 latency. The proposed research is significant because of the potential to define how latent viral reservoirs are established and maintained in secondary lymphoid organs.

Center for Linguistic and Cultural Democracy

Caribbean culture and arts will be celebrated throughout the summer with a series events including a four week costume making class, cultural workshops at local Caribbean restaurants and a cultural exchange workshop between Jamaica and Ghana highlighting their historic cultural and linguistic ties. The culminating event will be Caribbean Sea Fest on August 13th at Volunteer Park from noon until 8:00 pm. This project highlights the cultural expressions Cuba, Bahamas, Trinidad, Jamaica and Puerto Rico.

The Saint Paul & Minnesota Foundation

The Saint Paul & Minnesota Foundation ($1.2B in assets) supports nonprofits in MN through grants focused on education, community development, racial equity, arts. Awards range from $5,000 to $200,000.

The San Diego Foundation

The San Diego Foundation ($800M in assets) supports nonprofits in CA through grants focused on education, environment, community development, arts, health. Awards range from $2,500 to $200,000.

Parkview Services

Vibrant Palette, a nonprofit arts program for adults with I/DDS, collaborates with Belltown Arts Walk, The Slide Gallery, and the City of Seattle for 'The Small Things,' an inclusive arts extravaganza. From 1/8/24 through 2/4/24, we will hold workshops and public art viewing. The Small Things provides 3x3 canvases to up to 150 community members, hosts two free in-person workshops, and features an opening event for the displayed art at the Slide Gallery. This project, rooted in accessibility and inclusion, enhances participation in the Seattle arts community for adults with I/DDs.

Soufend Arts Council

The Soufend Arts Council will host a free event to celebrate the creativity, community, and culture of South Seattle. The event will feature an art exhibit, performances, and interactive art activities. It will be held August 24, 2019 from 2 pm - 8 pm on S Holly St between Rainier Ave S and 49th Ave S.

Sustainable Style Seattle

We have an ambitious vision for a "free store" that helps people find clothes they love and re-home clothes they no longer need, all for free. It will provide a much-needed way for people to keep things out of landfill and reform a harmful and exploitative system. The store will also provide a radically inclusive third place that helps people build skills, forge connections, be creative, and support art. We want to be an example of the future of Seattle, one that’s built on innovation, care, dignity, and abundance. This pilot is crucial in changing the narrative of what urban spaces can and should be. We will use the space for the free store and events, but we also want to uplift historically underserved artists by sharing our space. We plan to run for a total of 9 months. We’ll run an initial trial in January, a review and planning period from Feb-Apr, and an extended pilot from May-Sept. We plan to have 1 space, but we’ve had offers to create this concept in multiple spaces.

Belltown Butterflies

The Butterfly Effect—the idea that small actions can have profound impacts—the project invites individuals to tap into their creativity and reflect on how they engage with the world by including art made on small, individual butterflies. At the project's heart is an installation of hundreds of these butterflies made by different community members, symbolizing each person's significance in the fabric of society. Arranged in a flowing chromatic wave, the installation creates an immersive visual experience while fostering connection, self-awareness, and creative empowerment. The installation will be a part of a community art exhibition at Slip and Slide Galleries located at 2301 1st Ave Seattle WA for Belltown Artwalk on Sept 12, 2025, from 6-9 pm. The exhibition will run through Oct 5, 2025. Free and open to all, it enhances accessibility, equity, and public art awareness.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY/ABSTRACT The University of Texas Southwestern (UTSW) Medical Center is one of the premier academic medical centers in the world and requests support for a new research training program focused on training physician-scientists in the field of infectious diseases. The UT Southwestern Infectious Diseases (UTID) Research Training program will support 2 post-doctoral trainees for a two-year training period every year. The novel design of the UTID training program utilizes cross-campus recruitment for physician scientists working in the field of infectious diseases to create a large pool of candidates. Once recruited, trainees have an extensive interdisciplinary mentorship and a program-specific ID research training program that includes mentors and resources from 9 different departments, divisions, centers, and institutes across the medical campus. The 29 trainers have broad training and are comprised of a core group of highly accomplished, established investigators along with an expanding and impressive group of new and junior faculty mentors that embodies the intradisciplinary research programs across the UTID Training program that are bound by a common interest in combating infectious diseases. The UTID training program serves as an important focus for formal interactions among this overlapping group of talented trainers who have strong records of research success and outstanding records of training physicians and scientists. Our goal is to train post-doctoral physician-scientists for research careers in the molecular basis of microbial pathogenesis, cellular microbiology, host-defense mechanisms, regulation of virulence, structural biology, and clinical research. The research interests of the faculty include bacterial and viral pathogenesis, innate and adaptive immunity, antimicrobial therapeutic discovery, parasitology, RNA biology, and structural biology. The UTID Research Training program provides a strong emphasis on molecular mechanisms, molecular biology, and fundamental quantitative scientific approaches. Trainees who complete the program are expected to apply state-of-the-art molecular approaches to address important current and future problems in the field of infectious diseases. This training program will produce highly trained physician-scientists to address current and future challenges in the field of infectious diseases and immunology. This new program will also provide a pipeline for academic infectious disease research faculty for the region and throughout the US.

The Wichita Community Foundation

The Wichita Community Foundation ($500M in assets) supports nonprofits in KS through grants focused on education, community development, arts, health. Awards range from $2,000 to $100,000.

The Winnipeg Foundation

The Winnipeg Foundation manages a $1B+ endowment and provides grants to strengthen Winnipeg communities through arts, education, environment, health, and social services.

The Winston-Salem Foundation

The Winston-Salem Foundation ($400M in assets) supports nonprofits in NC through grants focused on education, community development, health, arts. Awards range from $2,000 to $100,000.

Toledo Community Foundation

Toledo Community Foundation ($300M in assets) supports nonprofits in OH through grants focused on education, community development, health, arts. Awards range from $2,000 to $75,000.

Engineering Bureau, Public Works

TOS - Task Order Solicitation

European Commission - HORIZON

Towards a fair and transparent market for cultural and creative content in the era of generative AI. Call: Culture, Creativity and Inclusive Society 2026. Programme: HORIZON. Keywords: Artificial intelligence, intelligent systems, multi agent systems, Business models, Copyrights, Data and image processing, Experimentally-driven research and innovation, High performance computing, Information systems, Machine learning, statistical data processing and applications using signal processing (e.g. speech, image, video), Trustworthy ICT, Visual arts, performing arts, design. Open call from the EU Funding & Tenders Portal.

Wasat Community

On the September 25th, Dawud Walid, an African American Muslim scholar, will guide South Seattle's Muslim community in discussion and dialogue on social justice and activism with the cultural perspective of Muslims. The event will be held at Rainier Arts Center, located at 3515 S Alaska St at 7pm. Wasat will follow up the next day by implementing a service project for community youth to distribute nourishing free meals made from surplus produce to those facing food insecurity.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary: Eosinophilic esophagitis (EoE) is a chronic, allergen-mediated, clinicopathologic disease, and a leading cause of upper gastrointestinal morbidity among children in the United States. It is characterized by esophageal eosinophilic infiltration and progressive fibrotic remodeling leading to debilitating dysfunction, dysphagia, and esophageal food impactions. Advances in understanding EoE pathophysiology have led to the development of clinical, endoscopic, histological, and molecular indices. While these metrics have enhanced our ability to identify EoE, essential gaps remain. Specifically, their limited accuracy in classifying disease activity status, stratifying severity and risk of fibrotic complications, and informing personalized therapy continues to constrain progress in optimizing patient care. The increasing prevalence of pediatric EoE reiterates the urgency to address these translational gaps through innovative approaches. To this end, during his K23 award, the Principal Investigator (PI), an Early Stage Investigator, identified distinct biochemical and architectural features that distinguished non- EoE controls from EoE, and active EoE (aEoE) from inactive EoE (iEoE) by using Raman spectroscopy (RS), stimulated Raman spectroscopy (SRS), and second-harmonic generation (SHG) microscopy. In this proposal, he will leverage the emerging paradigm shift toward integrative, multimodal markers — an approach yet to be applied in EoE, and build on his previous work to develop more comprehensive metrics of disease processes. He has preliminarily demonstrated that (a) Raman-RNA (biochemical-molecular) biomarker signature [area under the curve (AUC) = 0.937] outperforms Raman alone (AUC = 0.875) and RNA alone (AUC = 0.875) in differentiating aEoE from iEoE, (b) epithelial biochemical and structural changes correlate with subepithelial ECM and LPF, and (c) baseline esophageal glycogen, protein, and lipid content can classify responders from non- responders to non-biologic EoE therapies such as proton-pump inhibitors and topical corticosteroids. Advancing these innovations further, he will develop Raman-RNA biomarker signatures that stratify aEoE and iEoE and compare their diagnostic performance against existing activity indices (Aim 1), identify Raman-SRS-SHG signatures for fibrotic transformation by investigating how the epithelial biochemical changes relate to and predict subepithelial ECM and LFP (Aim 2), and in a prospective cohort, evaluate if the baseline esophageal biochemical, clinical, endoscopic, and histologic features predict response to dupilumab (Aim 3). The investigative team's expertise, proven track record, exciting preliminary data, established protocols, state-of-the- art resources, institutional support, and a motivated patient population position this project for success within the funding period. This innovative and interdisciplinary research will address critical translational gaps in EoE and improve clinical outcomes for children with EoE. It will also catalyze new avenues of investigation and technological innovations, establishing the PI as an independent investigator at the intersection of pediatric gastroenterology and translational research.

NCI - National Cancer Institute

PROJECT ABSTRACT Triple-negative breast cancer (TNBC) has the poorest prognosis among breast cancer subtypes due to its inherently aggressive clinical behavior and the absence of well-defined molecular targets. Achievement of pCR to neoadjuvant therapy has been widely recognized as a surrogate marker for improved long-term outcomes, including reduced risk of recurrence and enhanced overall survival. However, current neoadjuvant therapy stratification for TNBC is far from satisfying. With the conventional neoadjuvant chemotherapy (NAC), over half of TNBC patients do not achieve pCR and face poor prognoses. The new neoadjuvant chemoimmunotherapy (NACI) combined pembrolizumab with the NAC and has improved pCR and survival rates (by less than 10%), but also introduces substantial toxicity risks without reliable predictive methods to determine individual patient benefit. Given TNBC’s aggressive nature and lack of effective targeted therapies in practice, early identification of responders versus non-responders to a specific therapeutic regimen is of great important for assisting clinicians to tailor therapy accordingly. However, there is currently no method to foretell how much an individual patient may benefit from the addition of immunotherapy, nor to practically guide optimization of therapy on a patient-specific basis. Digital twin techniques have gained emerging attention in this context, which offer great promise for precision management of TNBC by integrating real-time clinical and multi-modal data into virtual patient models to support decision-making. However, their clinical adoption faces substantial challenges, including developing accurate predictive models capable of comparing multiple treatment options, ensuring continuous updates, and seamless integration into clinical workflows. To overcome these barriers, our study will establish cancer digital twins (CDT) to deliver reliable, real-time predictive metrics for personalized TNBC treatment. In particular, to support pre-treatment stratification (Aim 1), we will leverage the clinically available multi-modal data and state-of-the-art AI models to improve the accuracy of response prediction and benefit quantification, so identifying the optimal therapy option (i.e., NAC vs. NACI) for individual patient. To support on- treatment adaption (Aim 2), we will develop a mechanism-informed data assimilation framework to continuously update response prediction given individual monitoring data, so guiding a timely, interpretable adjustment of therapeutic regimens. To address implementation (Aim 3), we will assess the impact of real-world data heterogeneity on model uncertainty and bias, establish a CDT prototype to deliver model outputs within clinical workflows, and collect stakeholders feedback on its feasibility. We hypothesize that the developed CDT can not only accurately predict patient-specific response, but also provide a deployable workflow that assists clinical decision-making. Along with training to gain comprehensive understanding on real-world data heterogeneities, deployment considerations, and modern clinical trials for computational devices, this work will lay the groundwork for clinical validation and practical translation of personalized TNBC treatment optimization.

Town Hall Seattle

Town Hall Seattle will organize Community-Created Events in four Seattle neighborhoods to take place during the first half of 2018. Diverse Neighborhood Steering Committees will be convened to identify issues and topics of special interest to their communities. The committees will collaborate as co-creators with an Artist- or Scholar-in-Community to develop and produce three to five inclusive, culturally diverse arts and civics events for, about, and hosted at venues in, their neighborhood. The events will culminate in the four committees coming together to examine how their work strengthened bonds within their neighborhood, and amplified a neighborhood voice for greater Seattle. Town Hall's Inside/Out project takes an asset-based approach to community building.

Toys Not Included

Toys Not Included is a group of Seattle Artists who work to promote LGBTQA, BIPOC and Under-Privileged Youth Artists and work to remove barriers like submission fees, commissions, and “pay to play” models. Located at 2301 1st Ave Toys Not Included will be hosting year-round work that culminates with our annual street art show in July that features 100+ artists and thousands of attendees. There will be monthly Street Art Activity Centers that bring free, hands-on workshops to neighborhoods citywide. Community members will be able to create alongside professional street artists, contributing to community-created installations featured in the annual show. By combining education, youth leadership, and commission-free programming, it will shift street art from stigma to celebration, build equity, creativity, and cultural pride across Seattle. The project is free and open to the public. The project will be completed in the Summer of 2026.

NIGMS - National Institute of General Medical Sciences

Project Summary Signals that cells receive over time from a small set of pathways (e.g., BMP, Wnt, and TGFβ) shape their fate and phenotype during development, regeneration, and disease. Despite their central importance, signaling histories of individual cells are often inaccessible to direct observation, hindering quantitative analysis and obscuring their connection to eventual cell fate. This challenge is particularly pronounced in mammalian systems, where limited optical access and the constraints of size and timescale often render live imaging impractical. To address this issue, we have developed an approach to reconstruct the history of signaling activity in single cells based on endpoint fluorescence images. This is achieved by regulating CRISPR base editors to generate mutations in engineered target sites at rates proportional to the signal of interest. These mutations create a heritable record of signaling activity in the genome, which can be read out at a later time, together with the gene expression profile of the cells. Using this approach, we demonstrated that cells retain a memory of their past response level to BMP signaling for up to 18 days, providing a mechanism for long-term interactions between signals that can facilitate coordination of developmental processes over time. In this proposal, we will expand the scope and utility of our signal recording approach by extending its dynamic range to capture the broad spectrum of in vivo signal intensities and enabling simultaneous recording of the sequence and timing of two signaling pathways. We will also engineer mouse embryonic stem cells to record three key developmental pathways: BMP, Wnt, and Nodal. This will allow us to generate stem cell-derived embryo models and chimeric embryos to link cell fate and spatial organization at the onset of organogenesis with signaling activity at different time windows earlier in development. Additionally, we will investigate mechanisms that enable long-term changes in BMP responsiveness following an initial stimulation, without requiring differentiation. We will then test whether similar mechanisms exist in Wnt and Nodal pathways and assess their role in mediating long-term crosstalk between pathways. To achieve these goals, we will take an interdisciplinary approach combining gene editing, quantitative imaging, epigenomic assays, computational analysis, and generation of developmental models. The proposed goals build on my prior publications, recent preliminary data from our lab, and collaborations I have established since launching my lab. This research program will substantially advance the state of the art in molecular recording, transforming it into a technology that can be used in vivo, in mammalian systems to drive biological discovery. Our long term vision is to identify how signaling history controls cellular decision making during development, and how instructions that cells receive are coordinated over time to produce tissues with the correct number, types, and spatial arrangement of cells. Ultimately, this knowledge will inform strategies for tissue engineering, and open new avenues for understanding and treating diseases driven by dysregulated signaling.

NCI - National Cancer Institute

The goal of TRAQ-to-Quit is to increase the potency and efficacy of behavioral interventions for smoking cessation treatment in low-income communities by leveraging state-of-the art Internet-of-Things (IoT) technology to merge three evidence-based approaches into a single comprehensive, multilevel intervention: i.) brief pediatrician advice and referral to cessation services; ii.) novel behavioral tele-counseling that guides smokers towards establishing a smokefree home (SFH) as an initial step toward cessation; and iii.) the deployment of an IoT system consisting of an indoor air quality (IAQ) smart home device that collects continual, objective measures of IAQ and integrates them into both smokers’ home environments and a tele-counselor participant dashboard that enables individualized, data-guided advice/problem solving. The proposed treatment model builds on several of our previous trials, most notably the Kids Safe and Smokefree (KiSS) trial, which demonstrated the efficacy of a multilevel behavioral intervention initiated by pediatricians in safety-net systems on the promotion of long-term bioverified abstinence, and Project Fresh Air (PFA), which demonstrated efficacy in reducing in-home smoking and children’s tobacco smoke exposure (TSE) using residential air monitors that continually assessed indoor air quality and immediately provided feedback upon detection of elevated air particulate levels. Given that most unregulated smoking occurs in smokers’ homes and evidence that SFH adoption relates to long-term abstinence, TRAQ to Quit aims to bolster the KiSS trial’s limited home-level intervention components with a PFA-inspired, potentially powerful IoT home monitoring system. We will enroll 272 parent/caregiver smokers referred from safety-net pediatric health systems serving low-income areas. A 2-group randomized control trial design will be conducted with measures collected at baseline, 8- (end of treatment), 12- and 24-weeks after the target quit date to compare: i.) KiSS Usual Care (KiSS-UC) to KiSS + the state-of-the art IoT system (KiSS+IoT). The feedback from the IoT system is expected to augment treatment effects on home-level determinants of smoking behavior change (i.e., knowledge/awareness of in-home exposure risk; motivation to protect children from exposure). Evidence suggests that among low-income smokers, such changes can improve SFH achievement, self-efficacy, home support for cessation, and the fostering of a supportive accountability dynamic, all of which are mediators of long-term abstinence in prior trials. More potent interventions are necessary to reduce tobacco-related morbidity and mortality in low-income communities. Our proposed strategy allows two public health priorities to be simultaneously addressed: i.) maximizing long-term smoking cessation success and ii.) reducing TSE for other household occupants, including children. If TRAQ-to-Quit is efficacious, it presents an innovative, potent and pragmatic pediatric system-initiated telehealth intervention model that could ultimately be disseminated via linkages between pediatric systems and large service providers (e.g. state quitlines).