2001 Biomarkers, New Treatments
With LRI funding, Dr. Wakeland made a critical finding—a new explanation for immune system breakdown in lupus. Findings were published in the prestigious journal Science in 2006.
Dr. Wakeland’s research in mouse genetics had previously implicated a family of molecules (known as the SLAM family) in the development of autoimmunity in lupus.
His LRI grant aimed to characterize the role of the various SLAM family members in a mouse model of lupus.
In the Science article, Dr. Wakeland reported that in lupus-prone mice, having a SLAM family member known as Ly108 contributes to a breakdown in controlling the white blood cells of the immune system that produce antibodies, called B cells.
This breakdown causes the B cells to go haywire and start producing antibodies to elements of the mouse's own body (such as DNA), thereby leading to many of the manifestations of lupus.
“My initial funding from the LRI played a pivotal role in making these findings possible,” said Wakeland. “With that early funding we developed an antibody that was critical in helping the lead Science study author Chandra Mohan, MD, PhD, and the team determine the function of Ly108 in this study. Moving forward, the antibody will continue to be a valuable tool for the research community."
Dr. Wakeland has been to speak on the results of his LRI-funded work at dozens of national and international conferences.
“We can now begin to target this pathway,” said Dr. Wakeland upon release of the Science paper. “We’ve found a place that we can potentially intervene.”
In Dr. Wakeland’s view, lupus represents “not a huge defect, but rather an immune system that is a little out of balance. The best approach, rather than suppressing the entire immune system with harsh drugs, is to try to find a mechanism to re-establish the balance…you may not need a sledgehammer” Tweaking the Ly108 pathway could be one such way to restore the balance.
Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Kumar KR, Li L, Yan M, Bhaskarabhatla M, Mobley AB, Nguyen C, Mooney JM, Schatzle JD, Wakeland EK, Mohan C. Science. 2006 Jun 16;312(5780):1665-9.
Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus. Wandstrat AE, Nguyen C, Limaye N, Chan AY, Subramanian S, Tian XH, Yim YS, Pertsemlidis A, Garner HR Jr, Morel L, Wakeland EK. Immunity. 2004 Dec;21(6):769-80.
Based on his LRI discoveries, Dr. Wakeland won NIH funding in the amount of $1.95 million to continue his work on the SLAM gene family.