Photo of Shiv S. Pillai,  PhD, MBBS

Shiv S. Pillai, PhD, MBBS

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-5619
Fax: (617) 724-9648

Shiv S. Pillai, PhD, MBBS

Massachusetts General Hospital


  • Professor, Medicine, Harvard Medical School
  • Professor, Health Sciences and Technology, Harvard Medical School


Research Abstract

A major research interest is the study of mechanisms to enhance immunity against tumors using small molecules directed against an enzyme that controls the strength of the immune response.

Another area of interest is the study of how chronic lymphocytic leukemia develops at the earliest stages.

We are also interested in the immune mechanisms that cause fibrosis, in diseases such as IgG4-related disease and scleroderma


Powered by Harvard Catalyst
  • Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, Stone JH. IgG4-related disease: Clinical and laboratory features in 125 patients. 2015. PubMed
  • Black JC, Atabakhsh E, Kim J, Biette KM, Van Rechem C, Ladd B, Burrowes PD, Donado C, Mattoo H, Kleinstiver BP, Song B, Andriani G, Joung JK, Iliopoulos O, Montagna C, Pillai S, Getz G, Whetstine JR. Hypoxia drives transient site-specific copy gain and drug-resistant gene expression. Genes Dev 2015; 29:1018-31. PubMed
  • Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet 2014. PubMed
  • Kai X, Chellappa V, Donado C, Reyon D, Sekigami Y, Ataca D, Louissaint A, Mattoo H, Joung JK, Pillai S. I虜B Kinase 硫 (IKBKB) Mutations in Lymphomas That Constitutively Activate Canonical Nuclear Factor 虜B (NF虜B) Signaling. J Biol Chem 2014; 289:26960-72. PubMed
  • Della-Torre E, Feeney E, Deshpande V, Mattoo H, Mahajan V, Kulikova M, Wallace ZS, Carruthers M, Chung RT, Pillai S, Stone JH. B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease. Ann Rheum Dis 2014. PubMed
  • Wallace ZS, Mattoo H, Carruthers M, Mahajan VS, Della Torre E, Lee H, Kulikova M, Deshpande V, Pillai S, Stone JH. Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum Dis 2014. PubMed
  • Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS, Deshpande V, Stone JH, Pillai S. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol 2014. PubMed
  • Della-Torre E, Mattoo H, Mahajan VS, Deshpande V, Krause D, Song P, Pillai S, Stone JH. IgG4-related midline destructive lesion. Ann Rheum Dis 2014. PubMed
  • Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH. IgG4-related disease. Annu Rev Pathol 2014; 9:315-47. PubMed
  • Ahmad M, Mahajan VS, Mattoo H, Stone JH, Pillai S. Individuals with IgG4-related disease do not have an increased frequency of the K409 variant of IgG4 that compromises Fab-arm exchange. J Rheumatol 2014; 41:185-7. PubMed
  • Pillai S. Rethinking mechanisms of autoimmune pathogenesis. J Autoimmun 2013; 45:97-103. PubMed
  • Pillai S. Love the one you're with: the HIV, B cell and TFH cell triangle. Nat Med 2013; 19:401-2. PubMed
  • Chellappa V, Taylor KN, Pedrick K, Donado C, Netravali IA, Haider K, Cariappa A, Dalomba NF, Pillai S. M89V Sialic acid Acetyl Esterase (SIAE) and all other non-synonymous common variants of this gene are catalytically normal. PLoS ONE 2013; 8:e53453. PubMed
  • Surolia I, Pirnie SP, Chellappa V, Taylor KN, Cariappa A, Moya J, Liu H, Bell DW, Driscoll DR, Diederichs S, Haider K, Netravali I, Le S, Elia R, Dow E, Lee A, Freudenberg J, De Jager 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, Pillai S. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 2010; 466:243-7. PubMed
  • Pillai S, Cariappa A. The follicular versus marginal zone B lymphocyte cell fate decision. Nat Rev Immunol 2009; 9:767-77. PubMed
  • Pillai S, Cariappa A, Pirnie SP. Esterases and autoimmunity: the sialic acid acetylesterase pathway and the regulation of peripheral B cell tolerance. Trends Immunol 2009; 30:488-93. PubMed
  • Brainard DM,Seung E,Frahm N,Cariappa A,Bailey CC,Hart WK,Shin HS,Brooks SF,Knight HL,Eichbaum Q,Yang YG,Sykes M,Walker BD,Freeman GJ,Pillai S,Westmoreland SV,Brander C,Luster AD,Tager AM. Induction of robust cellular and humoral virus-specific adaptive immune responses in HIV-infected humanized BLT mice. J Virol 2009; 83:7305-21. PubMed
  • 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; 206:125-38. PubMed
  • Pillai S, Cariappa A. The bone marrow perisinusoidal niche for recirculating B cells and the positive selection of bone marrow-derived B lymphocytes. Immunol Cell Biol 2009; 87:16-9. PubMed
  • Kosakovsky Pond SL, Poon AF, Zarate S, Smith DM, Little SJ, Pillai SK, Ellis RJ, Wong JK, Leigh Brown AJ, Richman DD, Frost SD. Estimating selection pressures on HIV-1 using phylogenetic likelihood models. Stat Med 2008; 27:4779-89. PubMed
  • White JH, Chiano M, Wigglesworth M, Geske R, Riley J, White N, Hall S, Zhu G, Maurio F, Savage T, Anderson W, Cordy J, Ducceschi M, Vestbo J, Pillai SG. Identification of a novel asthma susceptibility gene on chromosome 1qter and its functional evaluation. Hum Mol Genet 2008; 17:1890-903. PubMed
  • Leadbetter EA,Brigl M,Illarionov P,Cohen N,Luteran MC,Pillai S,Besra GS,Brenner MB. NK T cells provide lipid antigen-specific cognate help for B cells. Proc Natl Acad Sci U S A 2008; 105:8339-44. PubMed
  • Shimomura Y, Ogawa A, Kawada M, Sugimoto K, Mizoguchi E, Shi HN, Pillai S, Bhan AK, Mizoguchi A. A unique B2 B cell subset in the intestine. J Exp Med 2008; 205:1343-55. PubMed
  • Allman D, Pillai S. Peripheral B cell subsets. Curr Opin Immunol 2008; 20:149-57. PubMed
  • Pilcher CD, Wong JK, Pillai SK. Inferring HIV transmission dynamics from phylogenetic sequence relationships. PLoS Med 2008; 5:e69. PubMed
  • Benatuil L, Kaye J, Cretin N, Godwin JG, Cariappa A, Pillai S, Iacomini J. Ig knock-in mice producing anti-carbohydrate antibodies: breakthrough of B cells producing low affinity anti-self antibodies. J Immunol 2008; 180:3839-48. PubMed
  • Cariappa A, Boboila C, Moran ST, Liu H, Shi HN, Pillai S. The recirculating B cell pool contains two functionally distinct, long-lived, posttransitional, follicular B cell populations. J Immunol 2007; 179:2270-81. PubMed
  • Moran ST, Cariappa A, Liu H, Muir B, Sgroi D, Boboila C, Pillai S. Synergism between NF-kappa B1/p50 and Notch2 during the development of marginal zone B lymphocytes. J Immunol 2007; 179:195-200. PubMed
  • Moran ST, Cariappa A, Liu H, Boboila C, Shi HN, Holland PM, Peschon JJ, Pillai S. Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populations. Mol Immunol 2006; 43:1694-9. PubMed
  • Cavanagh LL, Bonasio R, Mazo IB, Halin C, Cheng G, van der Velden AW, Cariappa A, Chase C, Russell P, Starnbach MN, Koni PA, Pillai S, Weninger W, von Andrian UH. Activation of bone marrow-resident memory T cells by circulating, antigen-bearing dendritic cells. Nat Immunol 2005; 6:1029-37. PubMed
  • Cariappa A, Mazo IB, Chase C, Shi HN, Liu H, Li Q, Rose H, Leung H, Cherayil BJ, Russell P, von Andrian U, Pillai S. Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbes. Immunity 2005; 23:397-407. PubMed
  • Pillai S. Two lymphoid roads diverge--but does antigen bade B cells to take the road less traveled? Immunity 2005; 23:242-4. PubMed
  • Cariappa A, Shoham T, Liu H, Levy S, Boucheix C, Pillai S. The CD9 tetraspanin is not required for the development of peripheral B cells or for humoral immunity. J Immunol 2005; 175:2925-30. PubMed
  • Pillai S. Birth pangs: the stressful origins of lymphocytes. J Clin Invest 2005; 115:224-7. PubMed
  • Pillai S, Cariappa A, Moran ST. Marginal zone B cells. Annu Rev Immunol 2005; 23:161-96. PubMed
  • Pillai S, Cariappa A, Moran ST. Positive selection and lineage commitment during peripheral B-lymphocyte development. Immunol Rev 2004; 197:206-18. PubMed
  • Cariappa A, Chen L, Haider K, Tang M, Nebelitskiy E, Moran ST, Pillai S. A catalytically inactive form of protein kinase C-associated kinase/receptor interacting protein 4, a protein kinase C beta-associated kinase that mediates NF-kappa B activation, interferes with early B cell development. J Immunol 2003; 171:1875-80. PubMed
  • Moran ST, Haider K, Ow Y, Milton P, Chen L, Pillai S. Protein kinase C-associated kinase can activate NFkappaB in both a kinase-dependent and a kinase-independent manner. J Biol Chem 2003; 278:21526-33. PubMed
  • Chen L, Haider K, Ponda M, Cariappa A, Rowitch D, Pillai S. Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase. J Biol Chem 2001; 276:21737-44. PubMed
  • Cariappa A, Tang M, Parng C, Nebelitskiy E, Carroll M, Georgopoulos K, Pillai S. The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21. Immunity 2001; 14:603-15. PubMed
  • Cariappa A, Liou HC, Horwitz BH, Pillai S. Nuclear factor kappa B is required for the development of marginal zone B lymphocytes. J Exp Med 2000; 192:1175-82. PubMed
  • Chaudhuri S, Cariappa A, Tang M, Bell D, Haber DA, Isselbacher KJ, Finkelstein D, Forcione D, Pillai S. Genetic susceptibility to breast cancer: HLA DQB*03032 and HLA DRB1*11 may represent protective alleles. Proc Natl Acad Sci U S A 2000; 97:11451-4. PubMed
  • Ho SC, Chaudhuri S, Bachhawat A, McDonald K, Pillai S. Accelerated proteasomal degradation of membrane Ig heavy chains. J Immunol 2000; 164:4713-9. PubMed
  • Pillai S. The chosen few? Positive selection and the generation of naive B lymphocytes. Immunity 1999; 10:493-502. PubMed
  • Cariappa A, Kim TJ, Pillai S. Accelerated emigration of B lymphocytes in the Xid mouse. J Immunol 1999; 162:4417-23. PubMed
  • Wang JH, Avitahl N, Cariappa A, Friedrich C, Ikeda T, Renold A, Andrikopoulos K, Liang L, Pillai S, Morgan BA, Georgopoulos K. Aiolos regulates B cell activation and maturation to effector state. Immunity 1998; 9:543-53. PubMed