Pilot Core
Pilot or feasibility projects funded from the Alcohol Center of Research Nebraska will result in subsequent grant submissions to the NIAAA or other funding agencies to advance alcohol research.
Want to submit an application? Letter of Intent is due by January 1, 2024 and proposal is due by February 1, 2024. Click for more information.
We welcome applications for pilot projects that address biomedical research in alcohol misuse. ACORN is a NIAAA-funded alcohol center based at UNMC and the Omaha VA Research Service. The center’s mission is to work with the alcohol research community in the immediate region and beyond, conducting research activities that aim to discover the mechanisms of injury and illness that will lead to the implementation of effective prevention strategies.
Pilot Core 2023 Project Awardees
Pilot project duration is limited to 12 months and funding is limited to $25,000 per project. Pilot projects are primarily intended to assist investigators to obtain pilot data that can be used in pursuing support through other funding mechanisms.
Micah Schott, PhD, Assistant Professor, Department of Biochemistry and Molecular Biology
Approved Budget (7-1-23 to 6-30-24): $25,000
Abstract: Alcohol-associated liver disease (ALD) is a growing public health concern, and new therapeutic strategies are urgently needed to prevent its progression. This proposal establishes a collaboration between the laboratories of Dr. Micah Schott and co-investigator Dr. Rebecca Oberley-Deegan to investigate cellular mechanisms underlying ALD and explore the potential of antioxidant therapy using the ROS-scavenging agent BuOE to mitigate liver damage. The accumulation of lipid droplets (LDs) in hepatocytes plays a central role in ALD progression, and the role of LDs in facilitating hepatocyte damage, specifically through lipid peroxidation, is poorly understood. This project aims to define the impact of lipolysis on lipid peroxidation and cell damage in hepatocytes exposed to EtOH. Furthermore, the efficacy of BuOE, a promising SOD-mimic antioxidant, in reducing ROS-driven hepatocyte damage in ALD will be investigated using in vitro cell models and in vivo mouse models that recapitulate key features of human ALD. This study will provide preliminary data for future grant proposals to develop novel therapeutic interventions for ALD.
Shibiao Wan, PhD, Assistant Professor, Department of Genetics, Cell Biology and Anatomy
Approved Budget (7-1-23 to 6-30-24): $25,000
Abstract: Alcohol use disorder (AUD) is a type of addiction with adverse health, occupational, and social consequences. Existing neuroimaging studies indicate that AUD is a chronic relapsing brain disease, and it is related to aberrant functional connectivity (FC) in a unifying triple network. However, these studies have following limitations: (1) the results might be statistically unreliable due to the insufficiency of multiple-comparison correction when dealing with millions of dimensions of brain networks; (2) the biomarkers studied were all within triple networks, whereas few attentions were paid to other brain networks; and (3) complex patterns in a multi-variate matter could not be detected. To address these concerns, we propose to develop a machine learning (ML) framework to automatically identify FC biomarkers from both within- and between-brain networks (including both the triple network and other brain networks) for AUD diagnosis. Our proposed ML model is extensible to study other addictions and neurological disorders.
Siva S Koganti, PhD, Instructor, Department of Internal Medicine, Gastroenterology & Hepatology Division
Approved Budget (7-1-23 to 6-30-24): $25,000
Abstract: About 48% of HIV-infected individuals are alcohol abusers. Alcohol exposure tremendously potentiates HIV-induced liver fibrosis. The mechanisms behind these events are unclear. Emerging pieces of evidence point to the role of microRNAs (miRs) in EVs as the regulators of hepatic stellate cell (HSC) activation. We recently demonstrated that differentially expressed miRs in extracellular vesicles (EVs) released from alcohol-treated HIV-infected hepatocytes target mRNAs in HSC to regulate the activation of pro-fibrotic genes and liver fibrosis progression. In this context, we propose to functionally validate differentially expressed miRs and to target specific miRs with anti-miR treatment to attenuate fibrogenesis in alcohol-related and HIV-induced liver disease, which improves the quality of treatment and longevity in people living with HIV1 (PLWH) also having Alcohol Use Disorder (AUD) This illustrates the mechanism by which double-exposure to the virus (HIV) and ethanol regulates liver fibrosis progression. Thus, this study fully corresponds to the ACORN P50 grant mission.
Daniel R. Anderson, MD, Associate professor, Department of Internal Medicine- Cardiology
Approved Budget (10-1-23 to 6-30-24): $20,000
Abstract: Cardiovascular disease (CVD) is the leading cause of death worldwide. Recently, it has been demonstrated that ethanol consumption is an independent risk factor for the development of many forms of CVD. Unfortunately, the mechanisms by which ethanol causes CVD are not well understood. Our work will determine the electrophysiologic, biochemical, and molecular mechanisms by which EtOH and its metabolic by-products, acetaldehyde and malondialdehyde, affect cardiomyocytes. We hypothesize that ethanol and its oxidative metabolites disrupt the normal function and electrophysiology of cardiomyocytes, predisposing individuals to cardiovascular disease. To test this hypothesis, we propose two aims: Aim 1. Determine the effects of ethanol and its metabolites on the activity of cardiomyocytes. Aim 2. Determine the mechanisms by which by-products of ethanol metabolism alter cardiomyocyte function. Using human inducible pluripotent stem cells differentiated into beating cardiomyocytes, we will determine the effects of treatment with ethanol, acetaldehyde, and malondialdehyde on cardiomyocytes.
Amar B. Singh, PhD, Professor, Department of Biochemistry and Molecular Biology
Approved Budget (10-1-23 to 6-30-24): $20,000
Abstract: Alcoholic Pancreatitis (AP) is a potentially fatal inflammation of the pancreas; however, molecular understanding of its pathobiology is poor, which has a strong bearing on the clinical management. Dysregulated barrier function promotes inflammation. Tight junctions (TJs) help regulate the barrier function. The claudin family of proteins constitutes TJs where expression of claudin-2 increases during intestinal inflammation. Remarkably, claudin-2 is mutated in patients with AP and associates with an increased risk of AP. However, role of claudin-2 in AP is not known. In preliminary studies using mouse model of AP, we found significant upregulation in claudin-2 expression. This increase matched with simultaneous increases in expression of phospho-NFkB and phospho-Stat3. Based on these findings and the known association of claudin-2 with inflammation, we propose a causal role for claudin-2 in promoting AP, which will be tested in current proposal. We anticipate the outcome from proposed studies to be novel and clinically relevant.
We are not accepting proposal applications at this time. Our next RFA will open January 2024.
Examples of pilot or feasibility projects include:
- Initial support for developing novel, innovative, cutting-edge research, translation, prevention, or intervention approaches.
- Adapting and evaluating proven research tools or techniques for new applications or delivery systems.
- Obtaining preliminary data, mining existing state or national datasets, or pursuing critical data gaps.
- Supporting investigators from other fields of study to apply their expertise to alcohol use/misuse challenges.
- Developing new mechanisms for external or multicenter collaborative partnerships to address emerging alcohol use/misuse concerns.
- Exploring new directions that represent significant departures from established approaches, yet have the potential to yield great impacts.
