Susan A. Boackle, MD

University of Colorado Health Sciences Center, Denver, CO

2002 Biomarkers, Genetics

No one knows what causes lupus, although studies of families with more than one member with the disease suggest that a complex interaction between various genes and an unknown environmental factor may be to blame.

Dr. Boackle, on the hunt for clues to this gene (or genes), has shown that the gene for a critical immune system protein called Complement Receptor 2 (CR2) is likely responsible for susceptibility to lupus—at least in certain strains of mice.

With LRI funding, she investigated whether CR2 is somehow altered in humans with lupus as well, and might present a potential target for therapies.

To carry out her research, she used not only mouse models of lupus but human family studies, as well as laboratory studies done with cells from people with the disease.

Discovery! Ultimately, Dr. Boackle helped to identify a new altered form (a functional polymorphism) of the CR2 gene in lupus.

Select publications:

Wu, H.*, Boackle, S.A.*, Hanvivadhanakul, P.*, Ulgiati, D.*, Grossman, J.M., Lee,  Y., Shen, N., Abraham, L.J., Mercer, T.R., Park, E., Hebert, L.A., Rovin, B.H., Birmingham, D.J., Chang, D.-M., Chen, C.J., McCurdy, D., Badsha, H.M., Thong, B.Y.H., Chng, H.H., Arnett, F.C., Wallace, D.J., Yu, C.Y., Hahn, B.H., Cantor, R.M., Tsao, B.P.   Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus. Proc Natl Acad Sci 104: 3961-3966. 2007. (* These authors contributed equally to this work.)

S.A. Boackle, D. Ulgiati, V.M. Holers, L. Morel, K.M. Kaufman, and J. Harley.  Is CR2 a human lupus susceptibility gene?  Sequencing analysis of multiplex families.  Mol Immunol 41: 211, 2004 (abstract).

Cruickshank, M.N., Karimi, M., Fenwick, E., Mercer, T., Wu, H., Kaufman, K.M., Harley, J.B., Tsao, B.P., Boackle, S.A., Ulgiati, D. 2010. Functional analysis of single-nucleotide polymorphisms in the proximal promoter of human Complement Receptor 2 (CR2/CD21) (submitted 2010).

Ongoing funding:

With an Alliance for Lupus Research grant for $200,000 awarded in 2005, Dr. Boackle examined how the CR2 polymorphism impacts disease in people with lupus.

In collaboration with other groups at her institute, Dr. Boackle subsequently won a $1.75 million R01 grant and a $250,000 R21 grant from the National Institutes of Health to see how lupus progresses in people with different CR2 haplotypes.

Rev. July 2010