PEOPLE AND PROJECTS
|
|
Jerry works on several projects involving modulation of EAE by regulatory T cell populations.
|
|
Jerry Altz
Research Assistant
|
|
|
Recent studies using CD4+ transgenic T cells with a TcR reactive to PLP139-151 the immunodominant encephalitogenic epitope in SJL mice, demonstrate that naive T cell activation to myelin epitopes distinct from the priming epitope (epitope spreading), initiates in the CNS in R-EAE and TMEV-IDD, two murine models of multiple sclerosis (McMachon, et al. 2005). Samantha Bailey's work focuses on understanding the unique ability of CNS dendritic cells (DC) populations for driving naive T cell activation in the CNS. CNS DCs are not a homogenous population, and distinct populations exist that are phenotypically similar to DCs in secondary lymphoid organs. However, during the course of R-EAE, the CNS may provide a specialised environment determining the biology of DC subsets distinct to those at systemic sites.
|
|
Samantha Baily, Ph.D.
Research Associate
|
|
|
|
|
Byron Brunette
Research Assistant
|
|
|
|
|
Pam Carpentier
Graduate Student
|
|
|
|
|
Matt DeGutes
Research Assistant
|
|
|
|
|
Anne Ercolini, Ph.D.
Research Associate
|
|
|
Terra's project is focused on examining the mechanisms involved in promoting remyelination by oligodendrocyte progenitors in the CNS of adult mice where myelin has been damaged by T cell-mediated autoimmune processes. Terra's studies will utilize the R-EAE and Theiler's virus models of MS to apply both antigen specific immunoregulatory strategies, discovered in the lab, in combination with strategies aimed at promoting the expansion and differentiation of oligodendrocyte progenitors. The hypothesis is that this combinatorial approach will stop ongoing myelin damage in an antigen specific manner and promote repair of myelin.
|
|
Terra Fredrick, Ph.D.
Research Associate
|
|
|
Adam is currently investigating the therapeutic potential of non-mitogenic anti-CD3 immunotherapies as a method for restoring self-tolerance, as well as determing the role of CD4+CD25+ regulatory T cells during both the disease and recovery phases of autoimmune disease.
|
|
Adam Kohm, Ph.D.
Research Associate
|
|
|
|
|
Jeff McMahon, M.S.
Research Assistant
|
|
|
Intravenous administration of antigen coupled to splenocytes by ethlene carbodiimide results in the induction of peripheral T cell tolerance. This strategy is effective in preventing the induction of EAE as well as treating existing disease. Emma's project focuses on understanding the mechanism by which this treatment alters T cell function to result in tolerance.
|
|
Emma Feeney, Ph.D.
Research Associate
|
|
|
Joe studies the cellular and molecular mechanisms underlying the differential effect of structurally modified forms of anti-CD80 monoclonal antibody (mAb) in the CD4+ Th1 cell mediated disease model of PLP139-151-induced EAE. His findings suggest that stimulation of CD80 on a CD4+ T cell activated in Th1-promoting conditions induces an increase in the amount of IFN-gamma produced per cell and increases Th1 cell survival. These findings suggesting a mechanism by which anti-CD80 mAb treatment of PLP139-151-primed mice exacerbates disease, while treatment with anti-CD80 Fab fragments decrease disease severity. These studies offer a unique opportunity to determine the cellular and molecular mechanisms underlying the potent therapeutic effects of short-term mAb treatments, which may induce long-term antigen-specific tolerance.
|
|
Joseph Podojil, Ph.D.
Research Associate
|
|
|
Bettina is examining the expression and potential regulatory effects of costimulatory molecules
(CTLA-4, PD-L1 and PD-L2) on the various CNS antigen-presenting cell populations purified from the spinal cords and brains of mice undergoing R-EAE.
|
|
Bettina Schreiner, M.D.
Research Associate
|
|
|
We have shown that coupled-cell tolerance is significantly more effective then the i.v. administration of soluble peptide at both prevention and treatment of EAE and that soluble peptide administration after disease induction can in some circumstances lead to an IgE-mediated anaphylactic shock, which raises questions as to its practicality in a clinical setting. Recently, we have demonstrated that it is possible to ameliorate ongoing disease in which T cells specific for multiple myelin antigens are participating with cells coupled to a cocktail of encephalitogenic peptides. We are currently examining the possible mechanisms of coupled-cell tolerance induction.
|
|
Cassandra Smith
Graduate Student
|
|
|
I'm the lab manager and am proud to say that I've been here for 12 years...Wow!! Steve usually refers to me as the "real boss" in that I'm responsible for overseeing the daily operation and maintenance of the lab, as well as for managing the ever growing amount of grant money and personnel that Steve brings in for our research. I've dabbled in a number of research areas over the years, but now my focus has been on the continued development of reagents and protocols for our latest research tool, real-time PCR, and work with the Myelin Repair Foundation on two projects related to the characterization of myelin gene expression during CNS autoimmunity. This work will hopefully lead to identification of a candidate gene for use as a quantitative marker of the amount of demyelination and/or remyelination that we observe during our therapeutic efforts to modulate disease progression in our animal models of MS.
|
|
Wendy Smith Begolka, M.S.
Lab Manager
|
|
|
Meghann’s project concerns the CD8+ T cell response to Theiler’s murine encephalomyelitis virus (TMEV) in strains of mice that are either susceptible or resistant to TMEV-induced demyelinating disease (TMEV-IDD). Using methods such as antigen-specific tolerance, CD8+ T cell responses can be prevented or abrogated. Conversely, CD8+ T cell responses can be enhanced through the depletion of regulatory T cells. These experiments reveal the roles of virus-specific CD8+ T cells in this disease model.
|
|
Meghann Teague Getts
Graduate Student
|
|
|
Our lab has demonstrated that ECDI coupled cell tolerance (Ag-SP) is highly effective at inhibiting disease when given prior to disease onset or during progression. Coupled cell tolerance can be induced using both myelin specific peptides or whole proteins. We know that Ag-SP is antigen specific however we do not fully understand the mechanism of induction. Danielle is currently investing the mechanisms of ECDI coupled cell tolerance induction by examining interactions between donor coupled cells and host antigen presenting cell population with host T cells.
|
|
Danielle Turley
Graduate Student
|
|
|
|
|
Hong Zhang
Graduate Student
|
PAST MEMBERS
|
|
Mechanisms of Inhibition of autoimmune demyelinating disease by blockade of CD154-CD40 ligand pair interactions. Understanding the role of gd T cells in demyelinating disease. Drug screening and development for immune modulation of disease states in cancer and autoimmunity.
|
|
Laurence Howard, Ph.D.
Research Assistant Faculty
|
|
