# Center for Cellular Metabolism Research in Oklahoma > **NIH NIH P20** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2024 · $997,408 ## Abstract PROJECT SUMMARY/ABSTRACT The proposed studies will be done under the auspices of the parent COBRE award (P20GM139763). The goal of the parent award is to support research project leaders (RPL) to scientific independence in areas of cellular metabolism by creating and unifying resources under the Center of Cellular Metabolism Research in Oklahoma (CMRO). A multitude of complications can arise from type 1 (T1D) and type 2 (T2D) diabetes, which leads to a major burden on the healthcare system as medical care costs soar from these conditions. One of these complications occurring among patients with diabetes is non-alcoholic fatty liver disease (NAFLD) that can cause serious liver damage. NAFLD is a spectrum that ranges from isolated, relatively benign steatosis (NAFL) to the more harmful non-alcoholic steatohepatitis (NASH) associated with liver fibrosis. This liver damage pathogenesis involves a variety of cell types: in general NAFLD, but especially NASH, is hallmarked by chronic inflammation and heightened immune cell activity, which can activate hepatic stellate cells and endothelial cells, thereby resulting in a self-perpetuating pro-inflammatory and pro-fibrogenic network that can eventually progress into liver cirrhosis. However, the exact cellular contributions, and how these cells orchestrate the propagation of liver damage are not known, as previous studies mainly focused on the role of individual cell types rather than their interactions. To fully elucidate disease pathogenesis, it will be important to gain molecular insights into the reciprocal interactions between the main cell types that drive NAFLD progression, especially since the pathophysiological complexity of NAFLD has represented a challenge in the development of potential therapeutic targets, and there are currently no specific pharmacological treatments for NAFLD and/or NASH. Therefore, our proposal will address these knowledge gaps with regard to the basic mechanisms that promote diabetes-induced chronic liver disease in an in vivo setting. Herein, we will focus on examining the cell type-specific changes underlying T1D- and T2D-induced NAFLD/NASH in a cell-dependent manner. The combined expertise of Drs. Cleuren (endothelial cells), Gorman (immune cells), and Stout (hepatic stellate cells) is unique to this application, as this forms a highly synergistic approach to study diabetes-induced NAFLD pathogenesis. Elucidating not only the cell-specific molecular changes but particularly the cellular interactions, which would be lost if individual labs would only focus on their respective cell type of interest, is likely to uncover novel mechanisms that may lead to more effective therapies for NAFLD/NASH. Successful completion of this proposal will elucidate cell-specific differences underlying diabetes-associated complications. ## Key facts - **NIH application ID:** 11047345 - **Project number:** 3P20GM139763-04S1 - **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION - **Principal Investigator:** Lijun Xia - **Activity code:** P20 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $997,408 - **Award type:** 3 - **Project period:** 2021-02-05 → 2026-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11047345 ## Citation > US National Institutes of Health, RePORTER application 11047345, Center for Cellular Metabolism Research in Oklahoma (3P20GM139763-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11047345. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*