multiple sclerosis

Macrophages and dendritic cells (DCs) are phagocytic antigen presenting cells (APCs) of the mammalian immune system. The phagosome and endosome are intracellular organelles that are formed following phagocytosis and endocytosis of exogenous material by these cells. The lumen of these organelles is critical to the acquired immune response as it is the site of processing of exogenous antigen. In order for complex protein antigens to be presented to T cells, they must first be proteolytically processed within these microenvironments into small linear oligopeptides. These can then be loaded directly onto MHC-II molecules or exported to the cytoplasm for additional processing for MHC-I presentation (“cross presentation”). The chemistries within the phagosome and endosome affect both the generation efficiency and the repertoire of presentable oligopeptides. My lab over the past three years has been studying the microenvironment of phagosomes and endosomes.  The overall mission of our research program is to understand how antigen processing is controlled and modulated by microenvironmental parameters in the phago/endosomes of antigen presenting cells.  We further aim to exploit this knowledge to manipulate antigenic peptide repertoires, in order to enhance prevention and management strategies for specific disease states.  More recently, we have become invested in applying our basic findings to investigate manipulation of T cell populations in models of Multiple Sclerosis (MS). Our ultimate goal will be to identify agents that are able to manipulate antigen processing in MS, so as to decrease the generation of key peptides responsible for the initiation and maintenance of autoreactivity. This applied portion of the research program is being conducted in collaboration with Dr. Frank Jirik and is funded by the Multiple Sclerosis Society of Canada (MSSOC), with in-kind support from the EndMS foundation of Alberta.  We hope to become more integrated and active within the HBI MS program.

Another area of interest is working towards a standardized and validated definition of treatment failure and the risks and benefits of the various management options for those with aggressive and rapidly disabling MS including conventional chemotherapeutic agents and novel immunomodulators. I am also interested in the impact of pregnancy and reproductive hormones on MS activity.

Finally, I have an overall interest in clinical epidemiology and the design, methodology, and analysis of observational and clinical trials in MS and neurology in general.

I employ psychophysics and neuropsychological psychometrics to investigate sensitive reliable and valid outcome measures in MS. My approach includes a lateralized perspective to examine left-and-right cerebral asymmetries and the efficiency of interhemispheric integration of information. The overall goal of my research is to identify useful markers of central nervous system integrity and sub-clinical changes.

Dr. Costello's research focuses on the use of the anterior visual pathway as a system model of multiple sclerosis. Together with her colleagues, she is studying the mechanisms that underpin neurological disability in MS patients, with a view to developing new therapeutic strategies for the disease.

Dr. Costello regularly presents nationally and internationally in the areas of Neuro-Opthamology and Multiple Sclerosis. Together with her collaborators, she has secured over 2.5 million dollars in research funding from the Canadian National Institute for the Blind, the Multiple Sclerosis Society, Neuroscience Canada, and the Networks of Centres of Excellence, Stem Cell Network.

• I have developed a translational research program with Dr. V. Wee Yong to take therapies from the bench to bedside in multiple sclerosis. The first therapy in development is minocycline in which we are now undertaking a phase III RCT trial to prove efficacy. Other therapies are under development including Beta Crystalline (in collaboration with Dr. Shalina Ousman). In collaboration with Dr. Fiona Costello, we are developing an optic nerve model to test therapies for potential neuroprotective and repair benefits in phase II trials.
• I have established a dynamic population-based outcome study of patients (over 1200) ever-treated with MS disease modifying therapy in Southern Alberta. Utilization, cost and both clinical and patient-based outcome data are being collected.
• I have established a population-based cohort of over 1700 people with MS, linked to a serum bank, that includes people on MS therapy (above) but also people never treated.
• I have been studying ways to improve the ways we use corticosteroids to treat MS.
• With Dr. SB Patten, I have contributed to our understanding of depressive disorders in people with MS, including their association with MS disease modifying therapy and their impact on discontinuation of these therapies.