Chaim O. Jacob, MD, PhD

Dr. Jacob’s research interests include genetics and pathogenesis of systemic lupus erythematosus (SLE). He continues his groundbreaking work in discovering and characterizing new genes important to the development of SLE.

Dr. Jacob earned his medical degree from Tel Aviv University, Sackler School of Medicine. He then went on to complete graduate school at The Weizmann Institute of Science, followed by a Rheumatology Fellowship at Stanford University School of Medicine.

• The Henry Kunkel Society: Elected Member, 2009
• National Arthritis Foundation: Klinenberg Award, 2001-2002
• Southern California Chapter of Arthritis Foundation: Klinenberg Award, 2000
• Irvington House Institute for Medical Research: Fellow, 1988-1990
• The Reticulo Endothelial Society: Presidential Award, 1987
• J.F. Kennedy Memorial Prize, 1985

• Context-dependent induction of autoimmunity by TNF signaling deficiency JCI Insight. 2022 03 08; 7(5). . View in PubMed
• J Transl Autoimmun. 2021; 4:100075. . View in PubMed
• New Endothelial Mechanisms in Glomerular (Patho)biology and Proteinuria Development Captured by Intravital Multiphoton Imaging Front Med (Lausanne). 2021; 8:765356. . View in PubMed
• On the genetics and immunopathogenesis of COVID-19 Clin Immunol. 2020 11; 220:108591. . View in PubMed
• Development of Murine Systemic Lupus Erythematosus in the Absence of BAFF Arthritis Rheumatol. 2020 02; 72(2):292-302. . View in PubMed
• Essential role and therapeutic targeting of the glomerular endothelial glycocalyx in lupus nephritis JCI Insight. 2020 10 02; 5(19). . View in PubMed
• Ultraviolet light induces increased T cell activation in lupus-prone mice via type I IFN-dependent inhibition of T regulatory cells J Autoimmun. 2019 09; 103:102291. . View in PubMed
• Constitutive reduction in the checkpoint inhibitor, CTLA-4, does not accelerate SLE in NZM 2328 mice Lupus Sci Med. 2019; 6(1):e000313. . View in PubMed
• TLR7-Mediated Lupus Nephritis Is Independent of Type I IFN Signaling J Immunol. 2018 07 15; 201(2):393-405. . View in PubMed
• A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus Hum Mol Genet. 2018 07 01; 27(13):2392-2404. . View in PubMed
• Genetic fine mapping of systemic lupus erythematosus MHC associations in Europeans and African Americans Hum Mol Genet. 2018 11 01; 27(21):3813-3824. . View in PubMed
• Haploinsufficiency of NADPH Oxidase Subunit Neutrophil Cytosolic Factor 2 Is Sufficient to Accelerate Full-Blown Lupus in NZM 2328 Mice Arthritis Rheumatol. 2017 08; 69(8):1647-1660. . View in PubMed
• Transancestral mapping and genetic load in systemic lupus erythematosus Nat Commun. 2017 07 17; 8:16021. . View in PubMed
• Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production Ann Rheum Dis. 2016 Nov; 75(11):2007-2013. . View in PubMed
• Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture Arthritis Rheumatol. 2016 Apr; 68(4):932-43. . View in PubMed
• Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity Elife. 2016 Feb 15; 5. . View in PubMed
• Identification of a Systemic Lupus Erythematosus Risk Locus Spanning ATG16L2, FCHSD2, and P2RY2 in Koreans Arthritis Rheumatol. 2016 05; 68(5):1197-1209. . View in PubMed
• Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA Ann Rheum Dis. 2016 Jan; 75(1):242-52. . View in PubMed
• Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus Clin Immunol. 2015 Dec; 161(2):157-62. . View in PubMed
• Differential Development of Systemic Lupus Erythematosus in NZM 2328 Mice Deficient in Discrete Pairs of BAFF Receptors Arthritis Rheumatol. 2015 Sep; 67(9):2523-35. . View in PubMed
• Systemic lupus erythematosus-associated neutrophil cytosolic factor 2 mutation affects the structure of NADPH oxidase complex J Biol Chem. 2015 May 15; 290(20):12595-602. . View in PubMed
• Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression Am J Hum Genet. 2015 May 07; 96(5):731-9. . View in PubMed
• Nomenclature of Toso, Fas apoptosis inhibitory molecule 3, and IgM FcR J Immunol. 2015 May 01; 194(9):4055-7. . View in PubMed
• IgG1 protects against renal disease in a mouse model of cryoglobulinaemia Nature. 2015 Jan 22; 517(7535):501-4. . View in PubMed
• The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share Hum Mol Genet. 2015 Jan 15; 24(2):582-96. . View in PubMed
• Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus Genes Immun. 2015 Jan-Feb; 16(1):15-23. . View in PubMed
• Lupus nephritis susceptibility loci in women with systemic lupus erythematosus J Am Soc Nephrol. 2014 Dec; 25(12):2859-70. . View in PubMed
• GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region Genes Immun. 2014 Sep; 15(6):347-54. . View in PubMed
• Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription Am J Hum Genet. 2014 Apr 03; 94(4):586-98. . View in PubMed
• ABIN1 dysfunction as a genetic basis for lupus nephritis J Am Soc Nephrol. 2013 Nov; 24(11):1743-54. . View in PubMed
• Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry J Rheumatol. 2013 Jun; 40(6):842-9. . View in PubMed
• Development of systemic lupus erythematosus in NZM 2328 mice in the absence of any single BAFF receptor Arthritis Rheum. 2013 Apr; 65(4):1043-54. . View in PubMed
• Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups Ann Rheum Dis. 2013 Mar; 72(3):437-44. . View in PubMed
• Trans-ancestral studies fine map the SLE-susceptibility locus TNFSF4 PLoS Genet. 2013; 9(7):e1003554. . View in PubMed
• PTPN22 association in systemic lupus erythematosus (SLE) with respect to individual ancestry and clinical sub-phenotypes PLoS One. 2013; 8(8):e69404. . View in PubMed
• Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression PLoS Genet. 2013; 9(10):e1003870. . View in PubMed
• Admixture mapping in lupus identifies multiple functional variants within IFIH1 associated with apoptosis, inflammation, and autoantibody production PLoS Genet. 2013; 9(2):e1003222. . View in PubMed
• MicroRNA-3148 modulates allelic expression of toll-like receptor 7 variant associated with systemic lupus erythematosus PLoS Genet. 2013; 9(2):e1003336. . View in PubMed
• Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries Ann Rheum Dis. 2012 Nov; 71(11):1809-14. . View in PubMed
• Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus Arthritis Rheum. 2012 Nov; 64(11):3695-705. . View in PubMed
• Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian-European populations Arthritis Rheum. 2012 Nov; 64(11):3687-94. . View in PubMed
• A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus Genes Immun. 2012 Jul; 13(5):380-7. . View in PubMed
• Evaluation of TRAF6 in a large multiancestral lupus cohort Arthritis Rheum. 2012 Jun; 64(6):1960-9. . View in PubMed
• Genetics of rheumatoid arthritis: an impressionist perspective Rheum Dis Clin North Am. 2012 May; 38(2):243-57. . View in PubMed
• Analysis of autosomal genes reveals gene-sex interactions and higher total genetic risk in men with systemic lupus erythematosus Ann Rheum Dis. 2012 May; 71(5):694-9. . View in PubMed
• Dispensability of APRIL to the development of systemic lupus erythematosus in NZM 2328 mice Arthritis Rheum. 2012 May; 64(5):1610-9. . View in PubMed
• Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as susceptibility loci for systemic lupus erythematosus in a large-scale multiracial replication study Am J Hum Genet. 2012 Apr 06; 90(4):648-60. . View in PubMed
• Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis Genes Immun. 2012 Apr; 13(3):232-8. . View in PubMed
• Evidence for gene-gene epistatic interactions among susceptibility loci for systemic lupus erythematosus Arthritis Rheum. 2012 Feb; 64(2):485-92. . View in PubMed
• Lupus-associated causal mutation in neutrophil cytosolic factor 2 (NCF2) brings unique insights to the structure and function of NADPH oxidase Proc Natl Acad Sci U S A. 2012 Jan 10; 109(2):E59-67. . View in PubMed
• A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap PLoS Genet. 2011 Dec; 7(12):e1002406. . View in PubMed
• Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study Arthritis Rheum. 2011 Nov; 63(11):3493-501. . View in PubMed
• Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus Ann Rheum Dis. 2011 Oct; 70(10):1752-7. . View in PubMed
• Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups Arthritis Rheum. 2011 Sep; 63(9):2755-63. . View in PubMed
• Genetic analyses of interferon pathway-related genes reveal multiple new loci associated with systemic lupus erythematosus Arthritis Rheum. 2011 Jul; 63(7):2049-57. . View in PubMed
• Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort Genes Immun. 2011 Jun; 12(4):270-9. . View in PubMed
• Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility PLoS Genet. 2011 May; 7(5):e1002079. . View in PubMed
• B Cell and BAFF dependence of IFN-a-exaggerated disease in systemic lupus erythematosus-prone NZM 2328 mice J Immunol. 2011 Apr 15; 186(8):4984-93. . View in PubMed
• Reflections on Darwinian Evolution – Is there a Jewish Perspective? Rambam Maimonides Med J. 2011 Apr; 2(2):e0044.. View in PubMed
• Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus Nat Genet. 2011 Mar; 43(3):253-8. . View in PubMed
• Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production PLoS Genet. 2011 Mar; 7(3):e1001323. . View in PubMed
• Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes PLoS Genet. 2011 Feb; 7(2):e1001311. . View in PubMed
• Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study Am J Hum Genet. 2011 Jan 07; 88(1):83-91. . View in PubMed
• On anti-tumor necrosis factor-induced systemic lupus erythematosus J Rheumatol. 2010 Jan; 37(1):3-5. . View in PubMed
• The role of genetic variation near interferon-kappa in systemic lupus erythematosus J Biomed Biotechnol. 2010; 2010. . View in PubMed
• Deficiency of type I IFN receptor in lupus-prone New Zealand mixed 2328 mice decreases dendritic cell numbers and activation and protects from disease J Immunol. 2009 Nov 01; 183(9):6021-9. . View in PubMed
• A polymorphism within IL21R confers risk for systemic lupus erythematosus Arthritis Rheum. 2009 Aug; 60(8):2402-7. . View in PubMed
• Admixture in Hispanic Americans: its impact on ITGAM association and implications for admixture mapping in SLE Genes Immun. 2009 Jul; 10(5):539-45. . View in PubMed
• Identification of new SLE-associated genes with a two-step Bayesian study design Genes Immun. 2009 Jul; 10(5):446-56. . View in PubMed
• Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing Genes Immun. 2009 Jul; 10(5):457-69. . View in PubMed
• Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus Proc Natl Acad Sci U S A. 2009 Apr 14; 106(15):6256-61. . View in PubMed
• High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups Arthritis Rheum. 2009 Apr; 60(4):1085-95. . View in PubMed
• Evaluation of imputation-based association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) Hum Mol Genet. 2009 Mar 15; 18(6):1171-80. . View in PubMed
• Accelerated pathological and clinical nephritis in systemic lupus erythematosus-prone New Zealand Mixed 2328 mice doubly deficient in TNF receptor 1 and TNF receptor 2 via a Th17-associated pathway J Immunol. 2009 Feb 15; 182(4):2532-41. . View in PubMed
• Function2Gene: a gene selection tool to increase the power of genetic association studies by utilizing public databases and expert knowledge BMC Bioinformatics. 2008 Jul 17; 9:311. . View in PubMed
• Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci Nat Genet. 2008 Feb; 40(2):204-10. . View in PubMed
• Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform Arthritis Rheum. 2007 Dec; 56(12):4164-73. . View in PubMed
• Paucity of clinical disease despite serological autoimmunity and kidney pathology in lupus-prone New Zealand mixed 2328 mice deficient in BAFF J Immunol. 2006 Aug 15; 177(4):2671-80. . View in PubMed
• The mouse cell surface protein TOSO regulates Fas/Fas ligand-induced apoptosis through its binding to Fas-associated death domain J Biol Chem. 2005 Mar 11; 280(10):9618-26. . View in PubMed
• A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes Nat Genet. 2004 Aug; 36(8):837-41. . View in PubMed
• Pivotal role of Stat4 and Stat6 in the pathogenesis of the lupus-like disease in the New Zealand mixed 2328 mice J Immunol. 2003 Aug 01; 171(3):1564-71. . View in PubMed
• Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis J Immunol. 2003 May 01; 170(9):4818-25. . View in PubMed
• Characterization of the FcgammaRIIA promoter and 5’UTR sequences in patients with systemic lupus erythematosus Genes Immun. 2002 Oct; 3 Suppl 1:S47-50. . View in PubMed
• Genetic and physical mapping of a type 1 diabetes susceptibility gene (IDDM12) to a 100-kb phagemid artificial chromosome clone containing D2S72-CTLA4-D2S105 on chromosome 2q33 Diabetes. 2000 Mar; 49(3):492-9. . View in PubMed
• Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families Hum Mol Genet. 1999 Apr; 8(4):639-44. . View in PubMed
• Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus Arthritis Rheum. 1998 Apr; 41(4):596-602. . View in PubMed
• Impaired nonrestricted cytolytic activity in systemic lupus erythematosus: involvement of a pathway independent of Fas, tumor necrosis factor, and extracellular ATP that is associated with little detectable perforin Arthritis Rheum. 1997 Jun; 40(6):1130-7. . View in PubMed
• Mutational analysis of TNF-alpha gene reveals a regulatory role for the 3′-untranslated region in the genetic predisposition to lupus-like autoimmune disease J Immunol. 1996 Apr 15; 156(8):3043-50. . View in PubMed
• Cyclic nucleotide phosphodiesterase type IV participates in the regulation of IL-10 and in the subsequent inhibition of TNF-alpha and IL-6 release by endotoxin-stimulated macrophages J Immunol. 1995 Nov 15; 155(10):4909-16. . View in PubMed
• The cytokine network in the pathogenesis of systemic lupus erythematosus and possible therapeutic implications Springer Semin Immunopathol. 1994; 16(2-3):181-200. . View in PubMed
• Mouse tumor necrosis factor receptor type I: genomic structure, polymorphism, and identification of regulatory regions Int Immunol. 1993 Jul; 5(7):775-82. . View in PubMed
• Tumor necrosis factor and interferon gamma: relevance for immune regulation and genetic predisposition to autoimmune disease Semin Immunol. 1992 Jun; 4(3):147-54. . View in PubMed
• Tumor necrosis factor alpha in murine systemic lupus erythematosus disease models: implications for genetic predisposition and immune regulation Cytokine. 1991 Nov; 3(6):551-61. . View in PubMed
• Regulation of MHC class II antigen expressionOpposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. J Immunol. 1991 Feb 01; 146(3):899-905. . View in PubMed
• Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus Proc Natl Acad Sci U S A. 1990 Feb; 87(3):1233-7. . View in PubMed
• Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1 Proc Natl Acad Sci U S A. 1990 Feb; 87(3):968-72. . View in PubMed
• Tumour necrosis factor-alpha in murine autoimmune ‘lupus’ nephritis Nature. 1988 Jan 28; 331(6154):356-8. . View in PubMed
• In vivo treatment of (NZB X NZW)F1 lupus-like nephritis with monoclonal antibody to gamma interferon J Exp Med. 1987 Sep 01; 166(3):798-803. . View in PubMed

• Stohl, William
• Haiman, Christopher