Samuel David
Professor, Anatomy and Cell Biology; Neurology and Neurosurgery
PhD (Manitoba)
(1) CNS and Peripheral Nerve Injury. This work is focused on understanding the cellular changes and molecular mechanisms that trigger, as well as, switch off inflammation after CNS (spinal cord) and peripheral nerve injuries. We have identified several molecules that mediate inflammation after spinal cord injury and contribute to secondary tissue damage (neuronal loss and myelin damage). These include proteases, lipases, kinases, adhesion molecules and chemokines/cytokines. We also test small molecule compounds to target these inflammatory mediators to promote functional recovery after spinal cord injury. We also study the molecular mechanisms underlying the switching off of the inflammatory response after peripheral nerve injury and assess how these mechanisms operate in the CNS.
(2) Multiple Sclerosis. Our work on MS deals with the role of the phospholipase A2 (PLA2) family in the onset and progression of CNS autoimmune disease in mice called experimental allergic encephalomyelitis (EAE). This work has led to the discovery of excellent therapeutic targets for the treatment of the relapsing-remitting form of MS. Our current work is directed at testing new generation PLA2 inhibitors in vivo; the role of suppressors of cytokine signalling (SOCS) in chronic forms of EAE; and the role of molecules involved in iron homeostasis in the pathogenesis of EAE.
(3) Neurodegenerative Disease. This work focuses on the role of the ferroxidases in preventing iron accumulation and iron-mediated free radical injury in the CNS. Lack of these enzymes results in iron deposition and neurodegeneration in the CNS. We have identified and cloned a GPI-anchored form of a ferroxidase (ceruloplasmin), which is expressed by astrocytes in the CNS, and have generated a ceruloplasmin gene knockout mouse. We are currently characterizing other ferroxidases in the CNS; and the role of the iron efflux transporter, ferroportin, in the CNS. We are also studying the involvement of these iron homeostasis proteins in spinal cord injury and in mouse models of ALS and MS.
