Tobacco-Related Disease Research Program Funded Publications

Tobacco use remains the single most preventable cause of disease, disability, and death in the United States and in California. The Tobacco-Related Disease Research Program (TRDRP) is one of three entities that constitute California’s program to control tobacco consumption and alleviate the burden of tobacco-related disease. This effort was initiated by Proposition 99, “The Tobacco Tax and Health Protection Act of 1988” which mandated that the Department of Health Services, the Department of Education and the University of California be allocated a portion of the tobacco tax revenue collected to address issues of tobacco consumption and its consequences in the state. Enabling legislation requested that the University of California, in its role as the research arm of the state, “administer a comprehensive grant program to support research efforts related to the prevention, causes, and treatment of tobacco-related diseases” and that “ all qualified investigators, regardless of institutional affiliation, shall have equal access and opportunity to compete for the funds.”

The TRDRP is administered by the University of California and is a program of the Research Grants Program Office (RGPO), Office of Research and Graduate Studies at the University of California, Office of the President.

Sort By:

Show:

Class Dismissed: Examining Social Class Discrimination and Academic Achievement Among Adolescents

(2025)

Introduction

Economic inequality is rising around the globe. Social class includes income, education, and occupation, and is strongly tied to academic achievement. However, we do not yet know how the discrimination that adolescents experience because of their social class is associated with academic achievement. To address this knowledge gap, we examined the association between social class discrimination and academic achievement among adolescents.

Methods

Social class discrimination was measured with an adapted scale that was validated. The scale addressed overt and subtle forms and multiple sources, such as peers, school personnel, and store clerks. Data were collected in 2022. Participants included 1678 adolescents (42.61% cisgender girls) aged 13-18 years (M_age = 15.97) in the United States. Social class was measured with maternal education, a common indicator for adolescents. The sample included 49.2% whose mothers had earned less than a college degree.

Results

Hierarchical regression analyses indicated that social class discrimination was negatively associated with academic achievement, even after controlling for social class, age, and race/ethnicity. Moderation analyses revealed that the associations differed by age and social class. Effects were stronger for younger adolescents ( < age 15) than older adolescents ( > age 17) and among adolescents more advantaged in social class than those who were disadvantaged.

Conclusions

Social class discrimination was associated with academic achievement, even after controlling for social class. Findings offer the field a new mechanism for disrupting the strong association between social class and academic outcomes. Future research should consider how to develop programs that eliminate social class discrimination.

A dataset of chronic nicotine-induced genes in breast cancer cells

(2025)

These data show the differentially expressed genes (DEG) from HCC38 breast cancer cell line chronically exposed to nicotine versus vehicle control. Additional data is also provided from dynamic trajectory analysis, identifying the most dynamic genes due to chronic nicotine treatment. To produce this dataset, we first performed single cell RNA sequencing from HCC38 cells chronically treated with vehicle or nicotine, followed by scanpy analysis to yield 6 discrete cell clusters at conservative resolution. We then evaluated differential gene expression between chronic nicotine and control cells for each individual cluster or in the whole sample using PyDESeq2. For dynamic trajectory analysis, Velocyto (0.6) was used to estimate the spliced and unspliced counts for each gene between chronic nicotine-treated cells and vehicle, allowing computation of gene velocities. These data are useful for analysing the expression of individual genes or gene velocities either in the whole sample or in the different clusters identified. Since the HCC38 cell line used in these experiments is heterogeneous, including cells with features of stem-like, luminal progenitor-like and more differentiated cells, this dataset allows examination of the conserved as well as disparate gene expression effects of nicotine in different breast cancer cell types. Our dataset has a great potential for re-use given the recent surge in interest surrounding the role tobacco-use plays in breast cancer progression.

Cover page of Discrimination and Risky Health Behaviors: Examining the Association between Sources of Gender Discrimination and Tobacco Use Among Adolescent Girls

Discrimination and Risky Health Behaviors: Examining the Association between Sources of Gender Discrimination and Tobacco Use Among Adolescent Girls

(2025)

We examined the association between gender discrimination and tobacco use among 725 adolescent girls in the United States. Gender discrimination referred to the interpersonal prejudice individuals experienced because of their gender and included multiple forms (overt, subtle) and sources (teenagers, school personnel, and other important adults). Gender discrimination was measured with five subscales: overt gender discrimination from teenagers, overt gender discrimination from school personnel, overt gender discrimination from other important adults, subtle denial of gender discrimination, and subtle negative treatment. Tobacco use included four groups: no use, combustible tobacco use only, nicotine vaping use only, and dual use of these products. Multinomial logistic regression showed that overt and subtle forms of gender discrimination were positively associated with lifetime dual use compared to non-tobacco use. Overt discrimination from school personnel was positively associated with past month dual use compared to non-tobacco use. Social class and race/ethnicity moderated the associations, highlighting intersectionality.

S100A8/A9 innate immune signaling as a distinct mechanism driving progression of smoking-related breast cancers

(2025)

Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes. This required the α7 nicotinic acetylcholine receptor, which elicited dynamic changes in cell differentiation, proliferation, and expression of secreted cytokines, such as S100A8 and S100A9, as assessed by unbiased scRNA-seq. Indeed, pharmacologic or genetic inhibition of S100A8/A9-RAGE receptor signaling blocked nicotine's tumor-promoting effects. We also discovered Syntaphilin (SNPH) as an S100A8/A9-dependent gene enriched specifically in estrogen receptor-negative (ER^-) cancers from former smokers, linking this response to patient disease. Together, our findings describe a new α7 nAChR-S100A8/A9-Syntaphilin immune signaling module that drives nicotine-induced tumor progression and distinguishes smoking-related patient disease as a distinct subset of aggressive breast cancers.

An SSTR2–somatostatin chemotactic axis drives T cell progenitor homing to the intestines

(2025)

Progenitors of intraepithelial T cells (IELps) migrate from the thymus to the intestines after birth where they develop into unconventional TCRγδ and TCRαβ lymphocytes in a process of extrathymic lymphopoiesis within cryptopatches. Mechanisms of IELp migration have remained unclear. Here we show that thymic IELps express the somatostatin receptor SSTR2, which contributes to their homing to the gut. IELp homing is Sstr2 dependent and correlates with neonatal induction of Sst encoding somatostatin in neuroendocrine and lamina propria stromal cells. The SSTR2 ligands somatostatin and cortistatin attract IELps in chemotaxis assays and somatostatin triggers IELp binding to the mucosal vascular addressin MAdCAM1. T cell transduction with Sstr2 confers homing to the neonatal colon. Human fetal thymic IELp-like cells express SSTR2 and intestinal stromal cells express SST at the time of initial T cell population, suggesting conserved mechanisms of progenitor seeding of the developing intestines. These results reveal an unexpected role for the SSTR2-somatostatin axis in early immune system development and describe a new role for a small peptide hormone G-protein-coupled receptor in developmental lymphocyte trafficking.

Cover page of Effects of Cigarette Smoking and 3‐Day Smoking Abstinence on Translocator Protein 18 kDa Availability: A [18F]FEPPA Positron Emission Tomography Study

Effects of Cigarette Smoking and 3‐Day Smoking Abstinence on Translocator Protein 18 kDa Availability: A [18F]FEPPA Positron Emission Tomography Study

(2025)

With the many negative health consequences of cigarette smoking, quitting is known to improve health in multiple domains. Using positron emission tomography/computed tomography (PET/CT) scanning, our group previously demonstrated that smokers have lower levels than nonsmokers of translocator protein binding both acutely and following overnight abstinence. Here, we sought to determine the effects of longer smoking abstinence on this marker of gliosis for microglia and astroglia, as well as explore associations between the marker and smoking-related symptoms. This observational study was performed in an academic VA medical centre. Fifty-nine generally healthy Veterans who were either nonsmokers (n = 15) or smokers (n = 44) participated in the study. Participants completed an intake visit to evaluate for inclusion/exclusion criteria, [¹⁸F]FEPPA PET/CT scanning and a structural magnetic resonance imaging scan. Smokers were alternately assigned either to smoke to satiety (n = 24) before scanning or undergo three nights of continuous abstinence prior to scanning using contingency management (n = 20 completed this protocol and scanning). The smoker satiety group had a significantly lower mean whole brain (WB) standardized uptake value (SUV) for [¹⁸F]FEPPA binding than both the nonsmoking (-15.3%) and abstinent smoker (-12.3%) groups. The nonsmoking control and abstinent smoker groups had mean WB SUVs that were not significantly different from one another (3.0% group difference). In an exploratory analysis, a significant inverse relationship was found between WB SUVs and mood ratings for smokers, indicating that higher levels of TSPO binding were associated with worse mood. The central findings here support previous studies demonstrating lower levels of the marker for gliosis in satiated smokers and imply normalization with elimination of cigarette smoke constituents from the body, although other explanations for study results (e.g., alterations in radioligand delivery or clearance of radioligand by cigarette smoke constituents) are possible. These findings may represent a previously unknown health benefit of quitting smoking.

I Am My Peers: How Social Ties Influence E-Cigarette Attitudes, Policy Support, and Use

(2025)

Background

Electronic cigarette (e-cigarette) use is increasingly prevalent among youth and young adults, particularly college and university students. This is a population for whom e-cigarette use is not recommended due to potential health risks, including nicotine addiction and long-term respiratory effects. Social networks play a crucial role in shaping attitudes toward e-cigarettes and influencing use behaviors. However, the relative influence of different social ties-parents, siblings, and friends-on e-cigarette attitudes and use remains unclear.

Objective

This study utilizes data from the SMOKES study to compare the influence of e-cigarette use within different social network sections-parents, friends, and siblings-on personal e-cigarette attitudes and use among college and university students.