Shalina Ousman Lab

Multiple sclerosis (MS) is an autoimmune disease leading to central nervous system (CNS) degeneration in approximately 2.5 million people worldwide. Current therapies for MS are useful in some patients but they do not prevent progression of the disease and are ineffective in many patients thus underscoring a vital need for new therapies. My research interest is to (a) identify endogenous protective molecules and/or mechanisms in MS that suppress autoimmunity and CNS damage, (b) define their underlying cellular and molecular processes, and (c) mobilize the beneficial functions of the protective mechanism(s) to prevent the progression of MS.

One of the projects in my lab is to investigate the role of alphaB-crystallin (αBC) in the central nervous system as it relates to MS. αBC, a small heat shock protein, is the most abundant gene upregulated in the brains of MS patients. I, and colleagues, previously showed that αBC plays a protective role in experimental allergic encephalomyelitits (EAE), a model of MS (Ousman et. al., Nature 2007). αBC attenuated the pro-inflammatory activity and CNS infiltration of leukocytes and also suppressed hyperactivity and apoptosis of astrocytes. Most significantly, recombinant human αBC (rhuαBC) was therapeutic in ameliorating clinical EAE. This was an exciting discovery since it implicated αBC as a potential new therapy for MS. Ongoing work in the lab will determine whether the EAE results translate to MS ie. we will determine the effects of rhuαBC on the function of immune cells from normal subjects and MS patients. The lab is also investigating other protective molecules in MS.

Injury to the axons of peripheral nervous system (PNS) neurons from adult mammals generally results in regeneration of nerve fibers back to their target. In humans however, PNS axon regrowth is limited and this has been attributed in part to deterioration of the supportive environment that is primarily mediated by Schwann cells (SCs). SCs benefit damaged peripheral neurons by 1) secreting neurotrophic factors to maintain cell survival until re-contact with their target, 2) producing adhesion molecules that provide a substrate for axon elongation, 3) phagocytosing myelin associated axon growth inhibitors and, 4) remyelinating regenerating axons. In humans however, these positive functions of SCs are truncated when these glial cells are denervated for a significant amount of time as occurs when the injury is severe such as a transection as compared to a crush damage, the greater the distance of the injury site from the target and, the older and unhealthier the individual. Our lab is interested in understanding the molecular signals that control the beneficial functions of SCs following peripheral nerve injury so as to enhance and prolong the growth promoting state of these glial cells until regenerating axons regain contact with their targets.