A case study of inclusion of rural populations in research: Implications for science and health equity.

Dr. Noonan is a nurse scientist, certified addictions nurse and an Associate Professor in the Duke School of Nursing. She received her BSN at Boston College, her MS in Nursing at Georgetown University, her MPH and PhD at the University of Virginia and completed a Post-Doctoral Fellowship at the University of Michigan. Dr. Noonan’s research is focused on using community-engaged approaches to develop innovative health behavior change interventions, including digital interventions, with the goal of reducing risk for chronic diseases including cancer and cardiovascular disease. Dr. Noonan’s work has a strong focus on rural and medically underserved populations. Much of her work also focuses on tobacco cessation. She has been continuously funded by NCI for the past 5 years to examine text-based intervention approaches for tobacco cessation in rural and medically underserved populations. Dr. Noonan teaches and mentors students across all programs at DUSON and is the Co-Director of the Duke National Clinician Scholars Program.

Program Director, CTSA Special Populations Core
Program Director, Newborn Screening Evidence Review Group

Dr. Keisha Bentley-Edwards is the Associate Director of Research for the Samuel DuBois Cook Center on Social Equity and an Associate Professor at Duke University’s School of Medicine, Division of General Internal Medicine. She is the Co-Director of Duke’s CTSI Center for Equity in Research.  Dr. Bentley-Edwards’ research focuses on how racism, gender, and culture influence health and education outcomes throughout the lifespan, especially for African Americans. Her research emphasizes cultural strengths and eliminating structural barriers to support healthy development in communities, families, and students. Dr. Bentley-Edwards nurtures complex conversations around race and racism in ways that not only identify disparities but prompt meaningful strategies for remedying these disparities around infant and maternal health, cardiovascular disease, and kidney disease, as well as educational disparities. 

As a physician-scientist practicing clinical and biochemical genetics, I am highly motivated to seek improved therapy for my patients with inherited disorders of metabolism. The focus of our research has been the development of gene therapy with adeno-associated virus (AAV) vectors, most recently by genome editing with CRISPR/Cas9. We have developed gene therapy for inherited disorders of metabolism, especially glycogen storage disease (GSD) and phenylketonuria (PKU). 
1) GSD Ia: Glucose-6-phosphatase (G6Pase) deficient animals provide models for developing new therapy for GSD Ia, although early mortality complicates research with both the murine and canine models of GSD Ia. We have prolonged the survival and reversed the biochemical abnormalities in G6Pase-knockout mice and dogs with GSD type Ia, following the administration of AAV8-pseudotyped AAV vectors encoding human G6Pase. More recently, we have performed genome editing to integrate a therapeutic transgene in a safe harbor locus for mice with GSD Ia, permanently correcting G6Pase deficiency in the GSD Ia liver. Finally, we have identified reduced autophagy as an underlying hepatocellular defect that might be treated with pro-autophagic drugs in GSD Ia.
2) GSD II/Pompe disease: Pompe disease is caused by the deficiency of acid-alpha-glucosidase (GAA) in muscle, resulting in the massive accumulation of lysosomal glycogen in striated muscle with accompanying weakness. While enzyme replacement has shown promise in infantile-onset Pompe disease patients, no curative therapy is available. We demonstrated that AAV vector-mediated gene therapy will likely overcome limitations of enzyme replacement therapy, including formation of anti-GAA antibodies and the need for frequent infusions. We demonstrated that liver-restricted expression with an AAV vector prevented antibody responses in GAA-knockout mice by inducing immune tolerance to human GAA. Antibody responses have complicated enzyme replacement therapy for Pompe disease and emphasized a potential advantage of gene therapy for this disorder. The strategy of administering low-dose gene therapy prior to initiation of enzyme replacement therapy, termed immunomodulatory gene therapy, prevented antibody formation and increased efficacy in Pompe disease mice. We are currently conducting a Phase I clinical trial of immunomodulatory gene therapy in adult patients with Pompe disease. Furthermore, we have developed drug therapy to increase the receptor-mediated uptake of GAA in muscle cells, which provides adjunctive therapy to more definitively treat Pompe disease.
3) PKU: In collaboration with researchers at OHSU, we performed an early gene therapy experiment that demonstrated long-term biochemical correction of PKU in mice with an AAV8 vector. PKU is a very significant disorder detected by newborn screening and currently inadequately treated by dietary therapy. Phenylalanine levels in mice were corrected in the blood, and elevated phenylalanine causes mental retardation and birth defects in children born to affected women, and gene therapy for PKU would address an unmet need for therapy in this disorder.

Currently we are developing methods for genome editing that will stably correct the enzyme  deficiency in GSD Ia and in Pompe disease.  Our long-term goal is to develop efficacious genome editing for glycogen storage diseases, which will allow us to treat these conditions early in life with long-term benefits. 

Dr. Anushka Palipana is a Biostatistician in the Health Statistics and Data Science division at the Duke University School of Nursing. She earned her Ph.D. in Statistics from the University of Cincinnati and her B.Sc. in Statistics from the University of Peradeniya, Sri Lanka. Her research interests encompass longitudinal modeling, survival analysis, and the joint modeling of longitudinal and survival data, with a focus on their applications in health science.

Prior to joining Duke University School of Nursing, Dr. Palipana was a postdoctoral research fellow at Cincinnati Children's Hospital Medical Center (CCHMC). At CCHMC, her research involved designing and analyzing medical monitoring investigations and integrating geo- and bio-markers to enhance the prediction and early detection of disease progression in conditions such as lymphangioleiomyomatosis and cystic fibrosis.

Dr. Palipana has authored numerous peer-reviewed journal articles published in methodological and clinical journals, including CHEST, Biometrics, Pediatric Pulmonology, PLoS One, and the Journal of Cystic Fibrosis, among others.

Joseph McClernon, Ph.D., is a professor in the Department of Psychiatry and Behavioral Sciences and founder/director of the Center for Addiction Science and Technology (CfAST). He is the Associate Director of the Duke Clinical and Translational Science Institute (CTSI).  During his tenure with CTSI, his leadership has been critical to building a culture of evaluation and continuous improvement, in strengthening the institute’s partnership with North Carolina Central University and other regional partners, and in planning strategy and development for the institute. 

Dr. McClernon earned a Ph.D. in clinical psychology in 2001 from Southern Illinois University-Carbondale and completed a postdoctoral fellowship at Duke in 2002. He served as Director of the Addiction Division in Psychiatry and Behavioral Sciences from 2012-2020. His research is focused on increasing our understanding of tobacco use, developing new and more effective interventions to nicotine dependence, and informing the FDA’s regulation of tobacco products. He has served as a site-PI and Co-I for more than ten years in the Center for the Evaluation of Nicotine in Cigarettes (CENIC)— a national consortium that has provided the bulk of evidence to the FDA for informing national policies that will reduce nicotine in cigarettes to non-addictive levels, thus saving millions of lives. Dr. McClernon is now leading efforts to transition CENIC’s focus to public health interventions that ensure the new policy will be implemented in ways that enable equitable outcomes for marginalized groups. Other regulatory science research has evaluated the effects of nicotine in cigarettes on a model of cigarette experimentation, the impact of flavors in cigarettes and e-cigarettes, and the influence of product characteristics and policy on multiple tobacco product use. He has led other groundbreaking research on the influence of drug-associated environments on drug use, relapse, and treatment; tobacco use disparities among individuals with comorbid psychiatric (e.g., ADHD, serious mental illness) and health (e.g., HIV; chronic pain) problems.

Dr. McClernon has actively mentored early career individuals from high school students through early career faculty. His former postdoctoral fellows are faculty or staff scientists at academic medical centers, government agencies, and research institutes. He has been continuously NIH-, FDA-, and foundation- funded since 2002. He has authored/co-authored more than 170 peer-reviewed publications, has two patents, has served as chair of NIH grant review panels, and is the recipient of numerous awards including the Society for Research on Nicotine and Tobacco Jarvik-Russell New Investigator Award. In 2024 he was recognized for excellence in mentoring when he was awarded the Career Mentoring Award in Clinical Research by the Duke University School of Medicine.