Collaborative MS Research Center Award
$825,000; 4/1/08-3/31/13
Principal Investigator
Lloyd Kasper, MD
Co-Investigators
James Gorham, MD, PhD
Jason Moore PhD
Randolph J. Noelle PhD
Heather Wishart PhD
William Hickey MD
Jacqueline Smith PhD
Zbigniew Szczepiorkowski, MD, PhD
Purpose
The role of regulatory T cells in MS and their potential for turning off the immune attack, with the ultimate goal of conducting clinical trials.
Summary
The driving force of the immune attack on the brain and spinal cord in MS is thought to be the T cell. Recent research suggests some T cells have the potential to become regulatory T cells, or T regs, and possibly stop MS disease activity. Finding ways to rev up their protective activity in MS is the focus of this collaboration.
Lloyd Kasper, MD — who has a longstanding career in researching the immune attack in MS — is leading a stellar team to determine how these cells may fail people with MS. His collaborators span the fields of basic and clinical immunology as well as imaging, genetics and computer science, creating a topnotch team.
For the first aim of this award, Dr. Kasper joins with Randolph Noelle, PhD, who has made seminal contributions to our understanding of the function of T reg cells, and James Gorham, MD, PhD, a new investigator to MS research. Dr. Gorham has studied extensively the role of immune messenger protein TGF-beta in the conversion of disease-causing cells to T regs. These three investigators are collaborating to establish a mouse model for studying T cells that convert into T regs.
Also new to MS research is Jacqueline Smith, PhD, who is helping the team to investigate T regs in cell populations from people with MS. Dr. Smith heads a laboratory that works with researchers conducting clinical trials to look at drug mechanisms. She is examining the potential to generate large numbers of T regs from the T cells of people with MS in the laboratory using a cocktail of immune proteins.
A particularly exciting aim of this study is to identify the genes that control T regs in people with MS. Joining forces in this effort are Heather Wishart, PhD, a National MS Society grantee, and Jason Moore, PhD — a new face in MS research — a leader in genetics and computer science at Dartmouth. Together with Dr. Kasper, this group will use gene chip technology — developed at Dartmouth specifically from genetic material from people with MS — that includes 3000 SNPs (common genetic variations) from approximately 1000 candidate genes.
The team has developed a “bioinformatics” approach that takes into consideration the biological function of each neurological candidate gene and its location in biochemical pathways, and has reduced this set of 1000 genes to ten candidates believed to be most integral to inducing a shift to an anti-inflammatory T reg response. They are analyzing the effects on this biochemical pathway of approved and experimental MS treatments.
The potential of T regs for use as a therapeutic strategy has promise in MS treatment research, and this talented team is poised to bring us closer to its fruition.