UAMS collaborating faculty members are primarily the backbone to the overall functioning of the Center for the Study of Tobacco. Faculty participating in the Tobacco and Related Diseases Working Group are invited to participate in the Center for the Study of Tobacco as collaborating faculty. Faculty seeking to become collaborating members are invited to submit a brief profile that can be posted on the website to help facilitate collaborative work.
Gunnar Boysen, PhD
Department of Environmental and Occupational Health
Dr. Boysen received his MS in Biology (1996) and a PhD in Chemistry from University of Kaiserslautern Germany (2002) in collaboration with the University of Minnesota Cancer Center, Minneapolis, MN. He then pursued a post-doctoral fellowship at UNC before accepting a faculty appointment at University of Arkansas for Medical Science in 2008, where he is currently an Associate Professor of Environmental and Occupational Health. Dr. Boysen’s research interest has been in understanding the interplay between chemical exposure and nutritional or other lifestyle habits, such as diet selection and physical activity. To achieve this, he utilizes analytical chemistry tools to study carcinogen metabolism, how this is modified by nutritional components and the underlying mechanisms regulating corresponding enzyme activities. More recently he has focused on common metabolic pathways, using targeted and un-targeted mass spectrometry-based metabolomic approaches to improve diagnosis and treatment of lung cancer.
Boysen, G. (2017). The Glutathione Conundrum: Stoichiometric Disconnect between Its Formation and Oxidative Stress. Chemical Research in Toxicology, 30(5), 1113–1116. https://doi.org/10.1021/acs.chemrestox.7b00018
Boysen, G., Kenney, P. M. J., Upadhyaya, P., Wang, M., & Hecht, S. S. (2003). Effects of benzyl isothiocyanate and 2-phenethyl isothiocyanate on benzopyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism in F-344 rats. Carcinogenesis, 24(3). https://doi.org/10.1093/carcin/24.3.517
Boysen, G., Pachkowski, B. F., Nakamura, J., & Swenberg, J. A. (2009). The formation and biological significance of N7-guanine adducts. Mutation Research – Genetic Toxicology and Environmental Mutagenesis, 678(2), 76–94. https://doi.org/10.1016/j.mrgentox.2009.05.006
Hartman, J. H., Miller, G. P. G. P., Caro, A. A. A. A., Byrum, S. D. S. D., Orr, L. M. L. M., Mackintosh, S. G. S. G., … Boysen, G. (2017). 1,3-Butadiene-induced mitochondrial dysfunction is correlated with mitochondrial CYP2E1 activity in Collaborative Cross mice. Toxicology, 378, 114–124. https://doi.org/10.1016/j.tox.2017.01.005
Sappington, D. R., Helms, S. A., Siegel, E. R., Penney, R. B., Jeffus, S. K., Bartter, T. T., … Boysen, G. (2017). Diagnosis of lung tumor types based on metabolomic profiles in lymph node aspirates. Cancer Treatment and Research Communication, in Press(March 2017), 1–6. https://doi.org/10.1158/1538-7445.am2015-547
Sappington, D. R., Siegel, E. R., Hiatt, G., Desai, A., Penney, R. B., Jamshidi-Parsian, A., … Boysen, G. (2016). Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines. Biochimica et Biophysica Acta – General Subjects, 1860(4), 836–843. https://doi.org/10.1016/j.bbagen.2016.01.021
Parimal (Perry) Chowdhury, BS; MS; PhD; AGAF
University of Arkansas for Medical Sciences College of Medicine, Department of Cellular Physiology and Molecular Biophysics
- Parimal Chowdhury. Aminoguanidine (AG) induces pro-oxidant effect on AR42J cells, a Rat Pancreatic Tumor Cell line. Ann Clin & Lab Sci 47(5):217-225, 2017
- Parimal Chowdhury,PhD, Nisreen Akel,BS, Azemat Jamshidi-Parsian,MS, Dana Gaddy, PhD, Robert J. Griffin,PhD, Jai Yadlapalli,PhD and Maxim Dobretsov,PhD. Degenerative tissue responses to space-like radiation doses in a rodent model of simulated microgravity. Ann Clin & Lab Sci, 46 (2): 87-94, 2016
- ) Parimal Chowdhury and Kodethoor B. Udupa. Effect of Nicotine on Exocytotic Pancreatic Secretory Response: Role of calcium signaling. Tobacco Induced Diseases 11:1-9, 2013 (Listed in Faculty of 1000 on February 20, 2013)
Currently Funded Grants
NASA-ASGC NNX10AL28H. Oxidative stress in a Rat model of Pre-diabetes. Principal Investigator
Studies of Pre-diabetes Under Simulated Space Environment (Chowdhury, PI) 2. Studies of Endothelial Dysfunction under Simulated Space Environment (Pathak, PI)
Molecular and Genetic effects of Nicotine on Pancreatic Acinar Cell Injury-from oxidative stress to cell signaling and function
Pancreatic cancer is a deadly disease. Detection of the disease at an early stage and possible intervention will save lives. There is no possible way the mechanism of this disease development can be studied in humans. Genetic information available from the Human Genome Project shows a very close similarity of the rodent genetic make-up with the humans. Thus our plan is to study the development of this disease in rodents by exposing them directly to nicotine, a major component of cigarette smoking. We have selected nicotine because it is addictive and reinforces smoking behavior in smokers. In addition it has been shown that nicotine is a potential risk factor for pancreatic cancer. Numerous studies reported in isolated acinar cells or in mutant cell lines derived from rodents show alterations of pancreatic acinar cell function and activation of cell proliferative signaling parameters in response to nicotine. These investigations point to the fact that this agent could potentially be used to develop a toxicological or carcinogenetic animal model to induce and study this disease. Our objectives in the proposed investigation are to delineate the mechanisms by which nicotine may promote the induction of pancreatic disease. The proposed studies will focus on novel technologies for pancreatic cancer genetics. Our future goal is to seek for a possible intervention by which nicotine-induced disease process can be counteracted.
Nicotine and Cigarette Smoking effect on Type 2 Diabetes and Diabetic Neuropathy
The obese Zucker diabetic fatty male rat (ZDF/GmiTM- fa) is a widely used animal model of non-insulin dependent diabetes mellitus (NIDDM or type II diabetes), in contrast to the obese ZDF females that rarely develop NIDDM. Published reports suggest that obese ZDF females may become diabetic on high-fat diets and has the potential to become an important animal model of NIDDM especially in women where few models currently exist.
We plan to conduct studies in Zucker lean, Zucker Fatty (pre-diabetes) and Zucker diabetic fatty (overt diabetes) rats of both male and female species using nicotine and cigarette smoke exposure to explore progression of their effects on Type 2 Diabetes and Diabetic Neuropathy. The rationale for our proposal is based on the literature and the results of our own studies, and fact that smoking affects pancreatic function and peripheral insulin resistance which may be relevant to the onset and progression of diabetes as a metabolic disease. It is also likely to be relevant to diabetic peripheral neuropathy, one of earliest indicators of diabetic impairment in animals and in humans. Furthermore, diabetes is usually followed by severe renal, neural, and cardiovascular complications that has approached epidemic scale in the US. Therefore, an understanding of the mechanisms of this disease, and its complications, a search for the markers that may allow early detection, and the factors that affect the progression of diabetes is of critical importance.
Our proposal is focused on evaluation of the role of nicotine and tobacco smoking in progression of diabetes and associated peripheral neuropathy. Therefore it is well within the focus of the National Institutes of Health to support “studies that are directly related to disease mechanisms and health endpoints of tobacco smoking.” More specifically, our study will add to the understanding of effects and consequences of nicotine/cigarette smoke exposure on the oxidant/inflammatory status and peripheral sensory-motor functions of normal, pre-diabetic, and diabetic animals. We hypothesize that associated with nicotine/smoke exposure, impairment of insulin signaling is relevant to the progression of diabetes and diabetic neuropathy both as a metabolic and nerve disease.Our objectives to conduct these studies are twofold:1) To determine and differentiate the role of nicotine and cigarette smoke exposure as risk factors in Type 2 diabetes and 2) To determine the physiological functions of insulin receptors and insulin signaling in peripheral nervous system. Completion of this project is expected to provide insight into the differences in progression of Type 2 diabetes and diabetic neuropathy between male and female rats and their individual responses to nicotine and cigarette smoke exposures. The project is expected to have significant impact on Public Health.
Pebbles Fagan, PhD, MPH
Department of Health Behavior and Health Education
Dr. Fagan’s research aims to increase our knowledge on effective strategies to reduce tobacco- and cancer-related health disparities in racial/ethnic, socially disadvantaged, gender, sexual orientation, and marginalized groups. She uses team science approaches to examine social-environmental, behavioral, and biobehavioral factors associated with health disparities and tobacco use and exposure among different groups. She has expertise in developing survey and other assessment tools, conducting qualitative research, and developing mixed-methods studies that focus on youth and adult populations. Dr. Fagan also has expertise in conducting online studies and using social media to understand tobacco use behaviors and how media influences these behaviors.
- Soule EK, Maloney SF, Guy MC, Eissenberg T, Fagan, P. User-identified electronic cigarette behavioral strategies and device characteristics for cigarette smoking reduction. Addictive Behaviors, 2017;79:93-101. doi:10.1016/j.addbeh.2017.12.010.
- Fagan P, Pokhrel P, Herzog TA, Guy MC, Moolchan ET, Cassel KD, Franke A, Li X, Pagano I, Trinidad D, Sakuma K, Sterling K, Jorgensen D, Lynch T, Kawamoto CT, Guy, MC, Lagua I, Hanes S, Alexander L, Clanton MS, Graham-Tutt C, Eissenberg T. Addictive Carcinogens Workgroup. Sugar and aldehyde content in flavored electronic cigarette liquids. Nicotine Tob Res, 2017. doi:10.1093/ntr/ntx234.
- Felicitas-Perkins J, Sakuma K, Blanco L, Fagan P, Perez-Stables EJ, Bostean G, Xie B, Trinidad, D. Smoking consumption among Hispanic/Latino nationality groups and Whites, comparisons between California and the United States. Nicotine Tob Res, doi: 10.1093/ntr/ntx191.
Currently Funded Grants
Title of grant: Reducing Tobacco Smoke Exposures among African American Socially Disadvantaged Female Breast Cancer Survivors Living in Arkansas Rural Counties
PI and Co-Is: Pebbles Fagan, PhD, MPH (PI), Michael Preston, PhD, MPH (Co-I), Ronda Henry-Tillman, MD, FACS (Co-I), Tiffany Haynes, PhD (Co-I)
Funding agency: Arkansas Breast Cancer Research Program
Years for funding: 9/2017-8/2018
Summary abstract: There are critical gaps in our understanding of tertiary cancer prevention, including contralateral breast cancer among socially disadvantaged African American female breast cancer survivors. The study’s long-term goals are to reduce the burden of tobacco exposures, improve quality of life and functioning, and ultimately increase the length of survivorship among African American breast cancer survivors living in rural AR. The proposed pilot study will use semi-structured interviews and photovoice to increase our understanding of knowledge, attitudes, and behaviors related to smoking and secondhand smoke exposure among African American women breast cancer survivors and use focus groups to develop intervention messages designed to increase the voluntary implementation of smokefree homes.
Title of grant: Arkansas Center for Health Disparities (ARCHD)
Reducing tobacco smoke exposures among low income children and women caregivers in the Arkansas Delta Region
PI and Co-Is: Pebbles Fagan, PhD, MPH (PI of subproject), Katherine Donald, BA (Co-I), Naomi Cottoms, BA (Co-I), Anna Huff Davis, BS (Co-I), Keneshia Bryant -Moore, PhD (Co-I), Joseph Su, PhD (Co-I), Ping Ching Hsu, PhD (Co-I), James Raczynski, PhD, FACA (MPI of U54), Carol Cornell, PhD (MPI of U54)
Grant #: U54 MD002329-11
Funding agency: NIMHD/NIH
Years for funding: 9/2017-8/2022
Summary abstract: The long-term goal of this study is to reduce the burden of multiple tobacco exposures, improve access to preventive care, and reduce the risk for chronic diseases among socially disadvantaged African American women and children. Cigarette smoking prevalence among African American Arkansan women is nearly double the overall smoking prevalence for African American women in the United States. Socially disadvantaged African American women and children have poorer access to preventive health care, disproportionately higher rates of secondhand smoke exposure, and lower exposure to smokefree policies in the home compared to advantaged groups. There are enormous health care provider and infrastructure deficits in rural distressed counties in the AR Delta region, yet providers play an important role in motivating women to implement smokefree policies in the home to protect their children. Community health workers, who are from the community, could have a powerful influence on women’s’ adoption processes by increasing the awareness of the innovation—in this case, smokefree policies—and persuading them to consider, adopt, and sustain the innovation. This mixed-methods study will apply an implementation framework using the Diffusion of Innovation Theory, Health Belief Model, and Theory of Reasoned Action to guide the development and implementation of an intervention that aims to increase the adoption and implementation of comprehensive smokefree policies (ban on cigarettes, cigars, electronic cigarettes, hookah and safekeeping products from children) in the homes of socially disadvantaged African American women caregivers aged 18-50 years who live in the AR Delta region. Our transdisciplinary team, the Coalition for a Tobacco Free Arkansas, Tri-County Rural Health Network, and the University of Arkansas for Medical Sciences, will implement a small-scale randomized trial that tests the feasibility and compares the efficacy of the intervention group (community health worker + risk communication materials + brief motivational counseling + tobacco exposure feedback on the child) to the control group (risk communication materials) on the primary outcome, implementation of comprehensive smokefree policies in the home and the secondary outcomes, quitting and smoking reduction at 3, 6, and 12 months. Our aims are to 1) conduct semi-structured interviews among African American women caregivers (n = 30) and community health workers (n = 15) to understand multi-level and -domain factors that influence tobacco use and policy practices; 2) use the interview data to develop, adapt, pilot test the intervention prototypes using 6 focus groups of women caregivers (n = 48) and feedback from our Stakeholder Partnership Board; and 3) assess the influence of the intervention on the study’s outcomes (n = 206).
Title of grant: Quantitative and Qualitative Methods for MRTP Evaluation:
Using Concept Mapping to Inform the Measurement of Flavor Outcome Expectancies among Young Adults
PI and Co-Is: Pebbles Fagan, PhD, MPH (PI of subproject), Mignonne Guy, PhD (Co-I), Eric Soule, PhD (Co-I), Thomas Eissenberg, PhD (PI of P50)
Funding agency: NIDA/NIH
Years for funding: 9/2017-8/2018
Summary abstract. The Family Smoking Prevention and Tobacco Control Act (FSPTCA) banned characterizing flavors in cigarettes to protect young people from the harms of smoking. However, when the Food and Drug Administration (FDA) deemed electronic cigarettes (ECIGs) under its authority in 2016, ECIG flavors were not banned. The FDA has stated that the final deeming rule is an important step in combating the rise in ECIG use, but also expressed concern about the role that flavors play in tobacco product experimentation, dual/poly use, and switching from combustible tobacco (cigarettes and little cigars/cigarillos) to ECIG among youth and young adults. Ongoing research efforts such as The Population Assessment of Tobacco and Health (PATH) will provide robust data on transitions in tobacco use among young people, but may not capture adequately the role of flavors in these transitions. Indeed, critical gaps remain in the availability of psychometrically sound measurement tools that can measure how flavors influence tobacco initiation and exclusive ECIG use. Such tools are needed to inform FDA decisions regarding pre-market applications, modified risk claims, and marketing limitations concerning flavored tobacco products.
The goal of this study is to develop a psychometrically sound measurement tool that can help to assess the role of flavors in ECIG trajectories among young adult tobacco users. One strength of the proposed work is that it builds on the concept mapping studies completed as part of Center for the Study of Tobacco Products (CSTP), Project 4 at Virginia Commonwealth University (VCU). To accomplish the goal of developing a flavor outcome expectancies scale that can help to predict ECIG use outcomes among combustible tobacco users in future studies, our research team will complete three phases of psychometric testing. In the first phase, item reduction and content validity, we will use existing concept mapping data to generate items, reduce and revise these items, and then solicit feedback from a panel of experts regarding the content validity and structure of the items. In the second phase, qualitative assessment, we will conduct cognitive interviews (n=10) and focus groups (n=24) among young adults aged 18-35 to examine their understanding and comprehension of the proposed scale items. In the third phase, quantitative assessment and testing, we will recruit young adults aged 18-35 who are current combustible product users who have never used ECIGs (non-ECIG users) and dual users (ECIGs + combustible tobacco users) (n=280) to complete an online survey that will help us understand the internal consistency of the items and internal scale structure.
Title of grant: Understanding Risk Perceptions, Patterns of Use, and Health Impacts Related to Large/Premium Cigars Use among Young Adult African American Males
PI and Co-Is: Valandra Oliver, PhD, Pebbles Fagan, PhD, MPH (Co-I), Duston Morris PhD (Co-I)
Funding agency: Minority Research Center on Tobacco and Addictions
Years for funding: 9/2017-7/2018
Summary abstract. Cigarette smoking is high among African American males in Arkansas. However, it is not clear that smokers understand that cigars are composed of the same toxic and carcinogenic constituents found in cigarette smoke. Cigar smoking can cause oral, esophageal, larynx, and lung cancer, and cigar smokers have an increased risk for coronary heart disease and chronic obstructive lung disease. It is possible that many Arkansans may not be aware of or believe that there is a risk for using large cigars because few public health messages have focused on communicating the risk of cigar smoking. For example, African American males, who have a higher prevalence of cigar use compared to other male racial/ethnic groups, may think that it is “safer” to use large/premium cigars compared to cigarettes and small cigars/cigarillos. The long-term goal of this study is to develop health messages that communicate the risk of large cigars to African American males. The aims of this pilot study are to 1) conduct 4 focus groups with African American male college students to understand and compare knowledge, attitudes, behaviors and risk perceptions associated with cigarettes, cigars, and dual use of cigarette and cigars (n=24); 2) collect biological samples (e.g. saliva) to examine levels of carcinogens and nicotine metabolites among these smokers; and 3) conduct a survey across 4 four year rural colleges to understand the prevalence of cigar use including large cigar use, patterns of use, nicotine dependence, and risk perceptions. The data will be used to develop a large-scale study that tests intervention messages that communicate the risks of combustible tobacco products.
Ping-Ching Hsu, Ph.D., M.S.
Department of Environmental and Occupational Health
I am interested in investigating the metabolic impacts of tobacco use in the population by using metabolomics to better understand and predict toxins and metabolite markers in human as a result of tobacco use, as well as by using global methylation profiling to identify aberrant methylation changes responsive to environmental stimuli. My goal is to reduce health disparities in tobacco-related diseases by addressing the adverse health effects resulting directly from tobacco exposure and to further inform FDA rules and guidance that aim to reduce the impact of tobacco use on the nation’s health.
- Hsu PC, Lan RS, Brasky TM, et al. Menthol Smokers: Metabolomic Profiling and Smoking Behavior. Cancer Epidemiol Biomarkers Prev. 2017;26(1):51-60.
- Hsu PC, Lan RS, Brasky TM, et al. Metabolomic profiles of current cigarette smokers. Mol Carcinog. 2017;56(2):594-606.
- Hsu PC, Zhou B, Zhao Y, et al. Feasibility of identifying the tobacco-related global metabolome in blood by UPLC-QTOF-MS. J Proteome Res. 2013;12(2):679-691.
Currently Funded Grants
Metabolomic Profiling from the Arkansas Cardiovascular Health Examination Survey (ARCHES).
Funding agency: UAMS 2017 Center for the Study of Tobacco Pilot Award
Years for funding: 7/01/2017-6/30/2018
Cigarette smoking is the top cause of preventable deaths in the United States including deaths from lung cancer and cardiovascular diseases. The state of Arkansas has the third highest smoking prevalence rate (24.7%), and the second highest smoking attributable cancer deaths rate (39%) in the U.S. Although quitting smoking reduce lung cancer risk, other prevention strategies including lung cancer early detection are limited because there are no validated biomarkers of lung cancer risk for smokers. Therefore, we propose a novel and robust technology, namely metabolomics, to evaluate the health impact from tobacco product usage. Metabolites of both carcinogens and endogenous cellular pathways can be simultaneously determined using this technology to screen for unknown or unexpected changes in tobacco products.
The specific goals of this pilot feasibility study are to investigate the metabolic profiles, intermediate biomarkers, and their correlation among tobacco users (cigarette and smokeless) using human blood samples from the 2006-2008 Arkansas Cardiovascular Health Examination Survey (ARCHES), conducted by the Arkansas Department of Health (ADH). Our specific aims are:
- Using robust technology to determine metabolomic profiles for never, current smokers, and smokeless tobacco (ST) users.
- Compare intermediate biomarkers of adverse health outcomes (such as inflammatory markers and lipid profiles) for never, current smokers, and ST users.
- Identify metabolomics profiles that are correlated with the intermediate biomarkers of adverse health outcomes.