After spinal cord injury (SCI), the injury site is filled with cellular debris, especially myelin debris that creates a very unique lipid-dense environment. Macrophages are the predominant phagocyte that are responsible for debris-clearance, but this process is not only inefficient, it is also maladaptive. The excessive amount of myelin debris present at the injury site leads to formation lipid-laden macrophages (a.k.a. foamy macrophages) that become pro-inflammatory and contribute to tissue regeneration failure. In addition to macrophages, microglia and fibroblasts also become foam cells. Therefore, understanding the mechanisms of myelin debris uptake and catabolism after SCI may lead to novel therapeutic targets to promote repair after SCI. In this application, we will investigate the mechanism of myelin debris uptake as well as the export of its catabolic byproduct in macrophages, microglia, and fibroblasts after SCI. In addition, we will test the therapeutic potential of novel nanoparticles that can target the uptake and efflux mechanisms.

Public Health Relevance

Patients with spinal cord injury (SCI) suffer from permanent disabilities but have limited treatment and therapeutic options. A major impediment to spinal cord regeneration is the failure to clear cellular debris at the injury site. Much of this debris is from myelin, which creates a very unique lipid-dense environment. Excessive uptake of lipid in phagocytic cells transforms them into inflammatory cells that contribute to the pathogenesis of SCI. Thus, we propose to investigate the mechanisms of lipid uptake and efflux in phagocytic cells at the injury site, and target these processes to limit formation of lipid-laden cells and promote tissue repair.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Jakeman, Lyn B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Miami School of Medicine
Schools of Medicine
Coral Gables
United States
Zip Code
Hong, Le Thi Anh; Kim, Young-Min; Park, Hee Hwan et al. (2017) An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling. Nat Commun 8:533
Zhu, Y; Lyapichev, K; Lee, D H et al. (2017) Macrophage Transcriptional Profile Identifies Lipid Catabolic Pathways That Can Be Therapeutically Targeted after Spinal Cord Injury. J Neurosci 37:2362-2376
Hackett, Amber R; Lee, Jae K (2016) Understanding the NG2 Glial Scar after Spinal Cord Injury. Front Neurol 7:199
Hackett, Amber R; Lee, Do-Hun; Dawood, Abdul et al. (2016) STAT3 and SOCS3 regulate NG2 cell proliferation and differentiation after contusive spinal cord injury. Neurobiol Dis 89:10-22
Clausen, Bettina Hjelm; Degn, Matilda; Sivasaravanaparan, Mithula et al. (2016) Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling. Sci Rep 6:29291
Funk, Lucy H; Hackett, Amber R; Bunge, Mary Bartlett et al. (2016) Tumor necrosis factor superfamily member APRIL contributes to fibrotic scar formation after spinal cord injury. J Neuroinflammation 13:87
Zhu, Y; Soderblom, C; Krishnan, V et al. (2015) Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury. Neurobiol Dis 74:114-25
Soderblom, Cynthia; Lee, Do-Hun; Dawood, Abdul et al. (2015) 3D Imaging of Axons in Transparent Spinal Cords from Rodents and Nonhuman Primates eNeuro 2:
Zhu, Yunjiao; Soderblom, Cynthia; Trojanowsky, Michelle et al. (2015) Fibronectin Matrix Assembly after Spinal Cord Injury. J Neurotrauma 32:1158-67
Lee, Do-Hun; Lee, Jae K (2013) Animal models of axon regeneration after spinal cord injury. Neurosci Bull 29:436-44

Showing the most recent 10 out of 11 publications