IBBME Special Lecture: Mohammed Shamji
July 29 @ 11:00 am - 12:00 pm
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Inflammatory Pathology in Disc-Herniation Radiculopathy and the Local Application of Thermally-Responsive Biopolymers to Modify Behavioural Phenotype
Lumbar discectomy is among the most common operations performed by spinal surgeons. The quality of life restored by this operation is substantial, yet only 90% of patients realize quality of life improvements, with many developing lower extremity neuropathic pain constituting the failed back surgery syndrome population. This group is thought to have advanced neuronal disease precluding meaningful recovery.
Characterization of human intervertebral disc tissue confirms the presence of Th17-mediated autoimmune activation in the underlying degenerative cascade. A rodent model of disc-herniation radiculopathy where heterotopic disc tissue is placed in contact with either spinal nerve root (rat) or sciatic nerve (mouse) demonstrates both mechanical allodynia and gait asymmetry that require the presence of intramural macrophage migration. The long term sequelae of this heterotopic disc tissue is sensitization in the dermatomal distribution to normally sub-threshold peripheral noxious stimuli.
Local delivery of anti-inflammatory therapeutics modifies the behavioural phenotype and the ultimate dermatomal sensitization. Development of genetically-engineered thermally-responsive peptide biopolymers that gel at physiological temperatures offers the potential to sustain therapeutic release at the disc-nerve interface. Bi-domain fusion protein functionality is confirmed by retention of both thermal sensitivity of the depot domain and anticytokine activity of the therapeutic domain. In vivo application of such biocompatible and biodegradable agents reveals favourable biodistribution characteristics as well as disease-modifying bioactivity.
After completion of an MSc degree at Yale University in 1999 and medical school at Queen’s University in 2003, Dr. Shamji entered the neurosurgery residency program at the University of Ottawa. During his residency, he obtained a PhD in biomedical engineering at Duke University in the area of thermally responsive biopolymers for drug delivery to inflammatory pathology. In 2011, Dr. Shamji became a Fellow of the Royal College of Physicians and Surgeons of Canada and began one year of adult combined spine surgery fellowship training at the University of Calgary. In 2012, he was recruited to the Faculty of the Division of Neurosurgery at Toronto Western Hospital as a Surgeon-Scientist and staff neurosurgeon and was appointed as an Assistant Professor of Surgery at The University of Toronto. His research is defining the molecular mechanisms that underlie the transition from acute immune-mediated inflammatory radiculopathy to chronic neuropathic pain whereby limb hypersensitivity is observed without injurious stimulus and developing interventions to prevent or reverse that transition. He has recently earned external peer-reviewed grant funding from both AO Spine North America (2013) and Canadian Pain Society (2014).