Emanuela Castigli

Department	Medicine
Hospital Title	Associate in Medicine
Academic Title	Assistant Professor
Phone	617 919 2478
Fax	617 730 0582
Email	Emanuela Castigli
Location	One Blackfan Circle Karp Family Research Building Boston MA 02115

Research Overview

Emanuela Castigli's research is focused on the molecular basis of Primary Immunodeficiencies. She first used knockout mice to delineate molecular pathways affected in human immunodeficiency disorders. Her group generated CD40 deficient mice, BAFF and APRIL deficient mice, all models of Immunodeficiency disorders. APRIL and BAFF are members of the tumor necrosis factor (TNF) family of ligands expressed in monocytes/macrophages and dendritic cells. Her work on APRIL, BAFF and their receptors, TACI, and BAFF-Receptor (members of the TNF-Receptor family) revealed that the APRIL/BAFF-TACI and BAFF-BAFF-R interactions induce isotype switching in human and mouse B cells. In particular, she found the APRIL/BAFF-TACI axis plays a crucial role in the isotype switching to IgA, the type of immunoglobulin critical for mucosal immunity.

IgA deficiency (IgAD) and Common Variable Immunodeficiency (CVID) are the most common form of primary immunodeficiency in humans. The molecular basis of both deficiencies is complex and was, prior to Dr. Castigli's work, largely unknown. Her studies suggested that mutations in APRIL, BAFF, BAFF-R or TACI genes, or a defect in their expression or in their signaling pathway, may underlie some cases of IgAD and CVID. Indeed, recently her group was able to show that mutations in the TACI gene caused CVID and IgAD in a small but significant number of patients. The current focus of her lab is to screen for mutations in APRIL, BAFF and BAFF-R in CVID and IgAD and delineate the molecular pathways downstream of these molecules that lead to isotype switching to IgA. This approach has opened new ways for the genetic diagnosis of CVID and IgAD and that the identification of novel signaling pathways should lead to novel therapeutic approaches.

About Emanuela Castigli

Emanuela Castigli graduated from University of Florence, Italy.

Key Publications

• Castigli E., Scott S., Dedeoglu F, Bryce P., Jabara H., Bhan A, Mizoguchi E and R. S. Geha. Impaired IgA class switching in APRIL deficient mice. Proc. Natl. Acad. Sci. USA 2004 Mar 16; 101(11): 3903-8.
• Castigli E., Wilson S.A., Scott S., Dedeoglu F., Xu S., Lam K.P., Bram R.J., Jabara H. and R.S. Geha. TACI and BAFF-R mediate isotype switching in B cells. J. Exp. Med. 2005 January 3; 201 (1): 35-39.
• Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS. TACI is mutant in common variable immunodeficiency and IgA deficiency.Nat Genet. 2005 Aug;37(8):829-34.