Anne Nicholson-Weller

Anne Nicholson-Weller

Professor of Medicine

Our laboratory is interested in the normal regulation of the human complement system, and how inflammation is modified through complement activation. Two main projects are in progress at this time. The first project, done in collaboration with Dr. Lloyd Klickstein, involves defining the role of C1q and CD35, a receptor for C1q (1), in modulating inflammation. The C1q/C1q receptor axis is important in preventing autoimmunity, since a deficiency of C1q in humans has been found to almost invariably lead to a lupus-like syndrome with severe morbidity and mortality. The propensity of C1q deficiency to lead to autoimmunity has been confirmed by Walport, et al. using the C1q knock out mouse. C1q binds to apoptotic cells and a deficiency of C1q might lead to a defect in clearing apoptotic debris. The C1q receptor is also involved in immune complex trafficking, and reportedly has a role in reperfusion injury. Efforts are now underway to map the C1q binding site on CD35; and the binding site of CD35 on C1q. Mannose binding lectin (MBL), which is homologous to C1q, also binds CD35. Thus, CD35, by virtue of binding both C1q and MBL, has a central role in mediating recognition by the Innate Immune System. The mechanism of signaling by CD35 is being investigated.

The second project involves the biologic activity of ecto-calreticulin. Calreticulin is best known as an ER chaperone protein, but some of it is expressed at the cell surface despite the fact that it lacks a transmembrane domain. We are investigating the adaptor proteins that bind it to the cell surface, and its ability to bind C1q. The major adaptor protein for the ecto-calreticulin of human neutrophils is CD59, a GPI-anchored protein.

Contact Information

Beth Israel Deaconess Medical Center
Infectious Disease Div., Dana Bldg., Rm. 617
330 Brookline Avenue
Boston, MA 2215
p: 617-667-3307



Experimental Approach