Massachusetts General Hospital
MGH Cancer Center
Bldg. 149, 13th Street, Rm. 7219
Charlestown Navy Yard
Boston MA 02129
Lab Members: 3 Instructors/ 4 Postdoctoral Fellows/2 Graduate Students
B cell lineage commitment and tolerance We are interested in cell fate decisions during B cell development and memory B cell generation. We seek to ask how BCR signal strength, Notch2, NFκB p50, and the Hippo pathway contribute to lineage commitment events in B cell development. We are particularly interested in a novel pathway in which Sialic acid acetyl esterase (SIAE) and inhibitory receptors of the Siglec family regulate peripheral B cell tolerance.
Genetic variants and human autoimmunity A major area of interest is the genetic basis of human autoimmunity, especially the role of rare genetic variants in genes that regulate B cell tolerance. Exome sequencing and the detailed functional analyses of human B cells are major approaches being pursued.
Negative regulators in dendritic cells and enhancing immune responses to HIV and cancer
Our studies on SIAE and inhibitory Siglecs in B cells have led us to explore how similar pathways function in regulating signaling in murine and human dendritic cells. We seek to use our increasing knowledge of negative regulatory pathways in immune cells to develop novel protocols for immunization that may be applied to the generation of neutralizing antibodies against HIVgp140 trimers, and also to the design of personalized immunotherapy in cancer.
Cariappa A, Takematsu H, Liu H, Diaz S, Haider K, Boboila C, Kalloo G, Connole M, Shi HN, Varki N, Varki A, Pillai S. B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase. J. Exp Med. 2009, 206, 125-138. PMCID: PMC2626685.
Surolia I, Pirnie SP, Chellappa V, Taylor KN, Cariappa A, Moya J, Liu HY, Bell DW, Driscoll D, Diederichs S,Haider K, Netravali I, Le S, Elia R, Dow E, Lee A, Freudenberg J, DeJager PL, Chretien Y, Varki A,MacDonald ME, Gillis T, Behrens TW, Bloch D, Collier D, Korzenik J, Podolsky DK, Hafler D, Murali M,Sands B, Stone JH, Gregersen PK, and Pillai S. Functionally defective germline variants of sialic acidacetylesterase in autoimmunity. Nature, 466, 244-247.
Pillai S and Cariappa A. The follicular versus marginal zone B lymphocyte cell fate decision. Nature Reviews in Immunology 2009 9, 767-777.
Last Update: 12/13/2012