David Stirling, PhD
- Associate Professor, Department of Neurological Surgery
- Associate Professor, Department of Microbiology & Immunology, Anatomical Sciences & Neurobiology
Laboratory: Advanced Optical Imaging
Phone: 502-852-8054
Email David Stirling
Biography
Research Focus:
The Stirling laboratory uses advanced optical imaging techniques (e.g., two-photon spectral microscopy) to investigate intrinsic and extrinsic mechanisms of white matter degeneration in living tissue following trauma to the nervous system. A major thrust in the laboratory is to understand the role of microglia, the immunocompetent cells of the CNS, and blood-derived immune cells (neutrophils and monocytes) in central myelinated fiber degeneration following spinal cord injury (SCI). Utilizing two-photon intravital microscopy to image genetically encoded fluorescent proteins in these cells, his team tracks, quantifies, and interrogates the role of neuroinflammation in SCI pathophysiology as these dynamic events are unfolding in real time. Second, his team also focuses on intrinsic mechanisms of central myelinated fiber injury following trauma utilizing a combination of in vivo and ex vivo live spinal cord preparations to visualize the dynamic response of spinal axons to injury in real time. Techniques instrumental to our research include advanced optical imaging, flow cytometry, cellular, molecular, biochemical, and behavioural analyses.
It is hoped that the new knowledge gained from these basic science studies will uncover key mediators that play a role in axon and myelin damage, and pave the way for therapeutic interventions to promote tissue sparing and improve neurological outcome following human SCI. (Click this link for more research information)
Recent Publications:
1. Orem BC, Morehouse JR, Ames S, Burke DA, Magnuson DSK, Stirling DP. Direct Ryanodine Receptor-2 Knockout in Primary Afferent Fibers Modestly Affects Neurological Recovery after Contusive Spinal Cord Injury. Neurotrauma Rep. 2022;3(1):433-46. Epub 2022/11/08. doi: 10.1089/neur.2022.0044. PubMed PMID: 36337076; PMCID: PMC9622210.
2. Stirling DP. Potential physiological and pathological roles for axonal ryanodine receptors. Neural regeneration research. 2023;18(4):756-9. Epub 2022/10/08. doi: 10.4103/1673-5374.354512. PubMed PMID: 36204832.
3. Orem BC, Rajaee A, Stirling DP. Inhibiting Calcium Release from Ryanodine Receptors Protects Axons after Spinal Cord Injury. Journal of neurotrauma. 2022;39(3-4):311-9. Epub 2021/12/17. doi: 10.1089/neu.2021.0350. PubMed PMID: 34913747; PMCID: PMC8817717.
4. Orem BC, Rajaee A, Stirling DP. IP3R-mediated intra-axonal Ca(2+) release contributes to secondary axonal degeneration following contusive spinal cord injury. Neurobiology of disease. 2020;146:105123. Epub 2020/10/05. doi: 10.1016/j.nbd.2020.105123. PubMed PMID: 33011333; PMCID: PMC7686917.
5. Rajaee A, Geisen ME, Sellers AK, Stirling DP. Repeat intravital imaging of the murine spinal cord reveals degenerative and reparative responses of spinal axons in real-time following a contusive SCI. Experimental neurology. 2020;327:113258. Epub 2020/02/28. doi: 10.1016/j.expneurol.2020.113258. PubMed PMID: 32105708; PMCID: PMC7549695.
6. Orem BC, Partain SB, Stirling DP. Inhibiting store-operated calcium entry attenuates white matter secondary degeneration following SCI. Neurobiology of disease. 2020;136:104718. Epub 2019/12/18. doi: 10.1016/j.nbd.2019.104718. PubMed PMID: 31846736.
7. Casha S, Rice T, Stirling DP, Silva C, Gnanapavan S, Giovannoni G, Hurlbert RJ, Yong VW. Cerebrospinal Fluid Biomarkers in Human Spinal Cord Injury from a Phase II Minocycline Trial. Journal of neurotrauma. 2018;35(16):1918-28. Epub 2018/08/04. doi: 10.1089/neu.2018.5899. PubMed PMID: 30074872.
8. Pelisch N, Gomes C, Nally JM, Petruska JC, Stirling DP. Differential expression of ryanodine receptor isoforms after spinal cord injury. Neuroscience letters. 2017;660:51-6. Epub 2017/09/14. doi: 10.1016/j.neulet.2017.09.018. PubMed PMID: 28899787.
9. Orem BC, Pelisch N, Williams J, Nally JM, Stirling DP. Intracellular calcium release through IP3R or RyR contributes to secondary axonal degeneration. Neurobiology of disease. 2017;106:235-43. Epub 2017/07/16. doi: 10.1016/j.nbd.2017.07.011. PubMed PMID: 28709993.
10. Stivers NS, Pelisch N, Orem BC, Williams J, Nally JM, Stirling DP. The toll-like receptor 2 agonist Pam3CSK4 is neuroprotective after spinal cord injury. Experimental neurology. 2017;294:1-11. Epub 2017/04/27. doi: 10.1016/j.expneurol.2017.04.012. PubMed PMID: 28445714.
In press:
1. Ames S, Adams K, Geisen ME, Stirling DP. Ca2+ induced myelin pathology precedes axonal spheroid formation and is mediated in part by store-operated Ca2+ entry. Neural Regen Res. NRR-D-22-00622R1. Accepted for publication Oct. 11, 2022.