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Joint Pilot Project Program
Katie Cardarelli, Dean of the School of Public Health & Information Sciences (SPHIS), and Jeffrey Bumpous, Dean of the School of Medicine (SOM), developed the Joint Pilot Project Program with $250,000 to support novel, collaborative research projects forming the basis for new NIH ROI grant applications. The Joint Pilot Project Program offers valuable resources for SOM and SPHIS investigators to tackle pressing health and public health challenges.
2024-25 Projects & Investigators
Congratulations to the following researchers who received pilot project funding to support initiatives that launched in October 2024 and will run through December 2025.
Integrating artificial intelligence and gene editing to identify and validate epigenetic targets for nutrient-based interventions in fetal alcohol spectrum disorder
INVESTIGATORS
- Shao-yu Chen, PhD, Professor & Distinguished Scholar, Dept. of Pharmacology & Toxicology, School of Medicine
- Shuoyang Wang, PhD, Assistant Professor, Dept. of Bioinformatics and Biostatistics, School of Public Health & Information Sciences
ABSTRACT
Fetal Alcohol Spectrum Disorders (FASD) is the leading known cause of mental retardation without a recognized cure. There is an urgent need to develop effective preventive strategies. Growing evidence suggests that epigenetic regulators can mediate ethanol-induced adverse effects on early development, indicating their potential as therapeutic targets for preventing FASD. However, as these regulators may each influence complex downstream genes, efficiently identifying and validating the epigenetic targets for nutrient intervention and screening and prioritizing potential dietary supplements or nutrients targeting these targets is urgent and challenging. By integrating artificial intelligence (AI) and gene editing technologies, our planned new R01 grant aims to identify and validate epigenetic targets for nutrient intervention in FASD and to screen and prioritize potential dietary supplements or nutrients targeting these targets. We have assembled a robust and comprehensive team with complementary expertise in AI, gene editing, and FASD. However, we need strong preliminary data to support our hypothesis and the feasibility of the research works proposed in our new R01 application. The objectives of this pilot grant are to 1) produce essential preliminary data that support the scientific premise of our planned NIH R01 grant; 2) generate critical preliminary data that demonstrate the feasibility of using AI and gene editing approaches in the R01 grant; and 3) build and showcase a successful collaborative track record among multiple PIs and key investigators. We plan to achieve these objectives by pursuing the following three specific aims in this pilot grant. Aim 1: To identify and select appropriate public databases and search strategies for retrieving data that will be used to screen epigenetic regulators and to identify and prioritize potential epigenetic regulators using AI, and to develop, test, and optimize biologically informed AI models for identifying and prioritizing these epigenetic targets that mediate ethanol-induced adverse effects on early development. Aim 2: To test whether network pharmacology analysis can effectively screen and identify the potential dietary supplements or nutrients that can mitigate FASD by targeting key epigenetic targets. Aim 3: To test whether CRISPRi or CRISPRa can functionally validate the role of epigenetic targets in mediating ethanol induced adverse effects in human brain organoids and zebrafish embryos. This pilot project has been strategically designed to generate preliminary data essential for this planned new R01 application. With support from this grant, we anticipate we will achieve all objectives of this pilot project, significantly enhancing the competitiveness of our planned R01 application.
Exposome approach to environmental carcinogen exposures and breast cancer incidence
INVESTIGATORS
- Lu Cai, Professor, MD, MPH, Professor, Depts. of Pediatrics, Radiation Oncology, Pharmacology & Toxicology; Director, Pediatric Research Institute; School of Medicine
- Natalie DuPré, ScD, MS, Assistant Professor, Dept. of Epidemiology & Population Health, School of Public Health & Information Sciences
ABSTRACT
Radon, dioxins, arsenic, and cadmium are established environmental carcinogens that impact breast carcinogenesis in cell and/or animal studies. Recent epidemiologic studies have reported associations between higher county-level radon, closer proximity to dioxin emission sources, and higher census-tract level ambient metals to increased risk of breast cancer (BC) subtypes, notably estrogen receptor negative BC. However, there are no epidemiologic studies of individual-level exposures to radon in the home and to dioxins in relation to BC incidence. The goals of this study are to: 1) conduct individual-level measurements of radon, dioxins, arsenic, and cadmium in a clinical BC case-control study and 2) construct long-term exposure history to these carcinogens using existing environmental databases of radon and ambient estimates of dioxins, arsenic and cadmium and applying these to the study participants’ prior residential addresses. In this clinical case-control study, we will recruit and consent 150 incident BC cases and 150 controls from the UofL Brown Cancer Center breast care clinic. Radon kits will measure home radon levels and wearable devices (i.e. a silicone wristband) will measure dioxins in a subset of participants (Aim 1). This is novel since, neither radon nor dioxins exposures have been collected in existing epidemiologic studies of BC. Urine, blood and nail clippings will be collected and a subset measured for arsenic and cadmium (and 23 additional metals) (Aim 2). Consented participants will complete a detailed questionnaire with information on BC risk factors, housing characteristics, and current and past residences. Medical records will be reviewed for breast health information on genetic risk markers, other risk markers, and for cases, tumor and treatment information. Residential histories from the participant questionnaire and LexisNexis will be geocoded and linked to existing environmental databases of estimated radon, ambient dioxins, and ambient metals to construct long-term estimated exposure history. We will then compare the current exposure levels and long-term estimated exposure history in BC cases and controls adjusted for confounders to identify whether these may be novel risk factors for BC incidence. This approach will establish a protocol within the Brown Cancer Center to integrate individual-level environmental exposure measurements from biospecimens and at-home kits with BC research that can expand to other environmental exposures and/or Brown Cancer Center patient populations. Results on recent and long-term radon, dioxin, arsenic, and cadmium exposures as risk factors for BC will contribute to pilot data for a future R01 submission on environmental risk factors for BC subtypes.
Development of a novel intervention to improve treatment of liver disease in rural communities
INVESTIGATORS
- Michael E. Egger, MD, MPH, Associate Professor, Department of Surgery, School of Medicine
- Seyed Karimi, PhD, Associate Professor, Dept. of Health Management & Systems Sciences, School of Public Health & Information Sciences
ABSTRACT
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths in the United States and most commonly caused by cirrhosis. A leading cause of cirrhosis is hepatitis C virus infection (HCV). There are several points along the continuum of its development where interventions can either reduce the risk of developing HCC or recognize it early when it is potentially treatable. In previous research, our team has identified disparities in HCV and HCC treatment in Kentucky, particularly in rural areas in Eastern and Western Kentucky. The goal of this project is to develop a novel multi-level intervention to improve knowledge of HCV treatment and increase rates of HCC screening among providers in rural Kentucky communities. We propose to use this pilot project funding to conduct a needs assessment and solicit feedback from providers that will be used to develop the intervention, which aims to educate primary care providers on current recommendations for HCV treatment and screening for HCC in patients with cirrhosis. We will recruit providers based on the communities we have identified in previous work with high incidence of HCV/HCC and low treatment rates, mostly centered in rural counties in Eastern and Western Kentucky. We will conduct semi-structured interviews to better understand gaps and barriers to treatment in terms of guideline-concordant therapy. We will use the findings of the study to design a multi-level intervention to address the knowledge gaps and barriers identified. Through multidisciplinary collaboration, we will develop a multidomain intervention aimed to address liver disease and liver cancer disparities in Kentucky. The findings of the pilot project will be used to develop a competitive NIH R01 application. The targeted funding opportunity is “Interventions to address disparities in liver disease and liver cancer,” PAR-24-207. This is an NIH R01 with participation from the NIMHD, NIDA, and NCI.The stated objective of this initiative is to “develop and test multi-disciplinary and multi-level and/or multi-domain interventions that will effectively address liver disease and liver cancer disparities.” We will target the June 5, 2026 application deadline. This work directly aligns with the goals of the UofL Health Brown Cancer Center and SOM/SPHIS priorities to improve rural outreach and cancer care for rural members in Kentucky. We anticipate that this project will be one of the initial outreach programs to be supported by the new Center for Rural Cancer Education and Research.
Individual and Structural Factors of Prescription Weight Loss Drug Misuse Among People with Eating Disorders
INVESTIGATORS
- Cheri Levinson, PhD, Professor, Dept. of Psychological & Brain Sciences; Dept. of Pediatrics, School of Medicine
- Nicholas Peiper, PhD, MPH, Associate Professor, Epidemiology & Population Health, School of Public Health & Information Sciences
ABSTRACT
Eating disorders (EDs) are highly debilitating mental disorders associated with significant impairment, disability, and healthcare costs. People with eating disorders (PWED) have particularly high morbidity and mortality largely due to complications from medical comorbidities and death by suicide. Core aspects of EDs include fasting, compulsive exercise, vomiting, and laxative/pill use along with maladaptive cognitions focused on overvaluation of food, weight, and body. Recent research indicates that glucagon-like peptide-1 (GLP-1) agonists for weight loss pose significant risk for PWED through appetite suppression, calorie restriction, and rapid weight reduction. Despite the risks, GLP-1 agonists and other weight loss drugs are frequently prescribed without adequate screening protocols that consider key individual risk factors such as ED severity, psychiatric comorbidities, and disordered relationships with food or body image. Structural factors have also been shown to increase the likelihood of weight drug misuse and adverse health outcomes among PWED. For example, prominent digital health companies and brick-and-mortar weight loss clinics have expanded their services to include GLP-1 drugs and started aggressively marketing these rollouts to the public. Similarly, the Food and Drug Administration has also documented a large increase in illicit entities that have begun distributing counterfeit GLP-1 drugs on popular social media platforms as part of large-scale scam operations. The primary objective of this study is to investigate individual and structural factors associated with GLP-1 misuse and real-world outcomes among PWED. The proposed investigation will be a post marketing surveillance study using an observational-implementation hybrid approach to collect data from a purposive sample of PWED (N=1,000) on experiences with weight loss drugs, inappropriate and off-label prescribing, and exposure to drug marketing and counterfeit drug scams. Informed by the Interactive Systems Framework for Dissemination and Implementation, the specific aims include: (1) characterize individual and structural factors of GLP-1 misuse and adverse events among PWED and (2) develop a protocol for a hybrid type 1 effectiveness study to reduce GLP-1 misuse and adverse events among PWED. Findings will directly inform the design of multi-level interventions that address GLP-1 misuse among PWED, thereby helping clinicians and prescribers address an emergent public health problem.
