Ahad M. Siddiqui, Ph.D., conducts research into regenerative neuroimmunology, where combinatorial therapies that promote regeneration through modulation of the inflammatory response are used to improve functional recovery. Spinal cord injury (SCI) occurs due to traumatic insult to the spinal column that often results in paralysis. Recovery following injury is limited, and regeneration often fails due to a hostile microenvironment created by secondary injury events, such as cell death, demyelination, inhibitory molecules and inflammation. Current therapies do not adequately address these secondary events, and combinatorial therapies that target multiple injury features are needed. Dr. Siddiqui's laboratory is particularly focused on discovering synergies between different therapies using novel biomaterials, cells, small molecules, electrical stimulation and rehabilitation with the aim to target multiple features of SCI pathophysiology.
- Cell and gene therapies deliver immunomodulatory compounds following SCI. Therapeutic compounds can be delivered to the spinal cord through gene therapy directly to produce the compounds needed or through implantation of genetically modified cells that secrete the compounds. This allows for continuous drug delivery of compounds with short half-lives in areas that are not typically bioavailable.
- Novel biomaterial designs deliver cells and drugs to promote regeneration. Shapes, sizes, compositions and other features of biomaterial scaffolds can be modified to optimize regeneration.
- Combination regenerative and neuromodulatory approaches promote plasticity, regeneration and immunomodulation. Therapies that enhance regeneration and modulate locomotor circuitry may work together through different mechanisms to aid motor recovery following SCI.
- Machine learning and artificial intelligence approaches analyze histologic and immunohistologic images to advance data collection in neuroscience. Analysis of histologic samples can be time-consuming and prone to bias and user error. Machine learning and computer vision applications can be translated into neuroscience to improve data reliability and allow for more in-depth analysis.
Significance to patient care
The lack of effective treatments for SCI and unmet patient needs present great opportunities in regenerative medicine. The development of treatments to promote some level of recovery must involve the right combination of neuroprotection, neuroregeneration and neuroplasticity. Dr. Siddiqui's laboratory works to discover the best combinations and time-course of therapies that could most improve recovery. In addition, the discovery of interactions between different mechanisms of treatments will help advance a better understanding of the individual therapies to further enhance them. The development of novel technologies, such as gene therapy, genetically modified cell therapies and innovative devices, and the use of artificial intelligence will help advance practice and improve outcomes for patients with SCI.
- Member and work group leader, Early Career Advisory Committee, North American Spine Society, 2022-present.