Genomics Research Center
The David Z. Rosensweig Genomics Research Center is applying genomic approaches to understand the causes and mechanisms of musculoskeletal and inflammatory conditions, including rheumatoid arthritis, osteoarthritis, tendon degeneration and associated muscle weakness, and bone loss in osteoporosis and orthopaedic implant loosening. The goal is to use this knowledge to develop personalized and effective new therapies that will restore mobility, enhance quality of life, and improve surgical outcomes for patients with rheumatologic and orthopedic disorders.
Established in 2013 with support from The Tow Foundation, the Genomics Center brings together a multidisciplinary team of scientists, clinicians, and computational biologists. The Genomics Center uses transcriptomics, epigenomics, and single-cell genomics to study disease genes and pathways, and is developing novel precision medicine therapeutic strategies for musculoskeletal conditions.
The goal of the computational group within the Genomics Center is to provide a full-stack consulting and analytical services for participating scientists and clinicians. We provide advice on experimental design, choice of appropriate technologies and analytical methods, perform data quality control and analysis, and create user-friendly reports and publication-ready data visualizations.
Autoimmunity
Rheumatoid Arthritis (RA)
- Sokhi UK, Yuan R, Mishra B, Chinenov Y, Singaraju A, Chan KK, Bass A, Bell RD, Donlin L, Ivashkiv LB. Opposing regulation of TNF responses by IFN-γ and a PGE2-cAMP axis that is apparent in rheumatoid and immune checkpoint inhibitor-induced arthritis human IL-1β+ macrophages. 2025 Jul 15;14.
- Mishra B, Bachu M, Yuan R, Wingert C, Chaudhary V, Brauner C, Bell R, Ivashkiv LB. IL-10 targets IRF transcription factors to suppress IFN and inflammatory response genes by epigenetic mechanisms. Nat Immunol. 2025 May;26(5):748-759.
- Loh C, Park SH, Lee A, Yuan R, Ivashkiv LB, Kalliolias GD. TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: transcriptomic and epigenomic analysis. Ann Rheum Dis. 2019 Sep;78(9):1205-1214.
- Mizoguchi F, Slowikowski K, Wei K, Marshall JL, Rao DA, Chang SK, Nguyen HN, Noss EH, Turner JD, Earp BE, Blazar PE, Wright J, Simmons BP, Donlin LT, Kalliolias GD, Goodman SM, Bykerk VP, Ivashkiv LB, Lederer JA, Hacohen N, Nigrovic PA, Filer A, Buckley CD, Raychaudhuri S, Brenner MB. Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.Nat Commun.2018 Feb 23;9(1):789.
- Stephenson W, Donlin LT, Butler A, Rozo C, Bracken B, Rashidfarrokhi A, Goodman SM, Ivashkiv LB, Bykerk VP, Orange DE, Darnell RB, Swerdlow HP, Satija R. Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic instrumentation.Nat Commun.2018 Feb 23;9(1):791.
- Orange DE, Agius P, DiCarlo EF, Robine N, Geiger H, Szymonifka J, McNamara M, Cummings R, Andersen KM, Mirza S, Figgie M, Ivashkiv L, Pernis AB, Jiang C, Frank M, Darnell R, Lingampali N, William R, Gravallese E, Bykerk VP, Goodman SM, Donlin LT; Accelerating Medicine Partnership: RA/SLE Network. Machine learning integration of rheumatoid arthritis synovial histology and RNAseq data identifies three disease subtypeArthritis Rheumatol.2018 Feb 22.
- Rao DA, Gurish MF, Marshall JL, Slowikowski K, Fonseka CY, et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis.2017 Feb ;542(7639):110-114.
- Loupasakis K, Kuo D, Sokhi UK, Sohn C, Syracuse B, et al. Tumor Necrosis Factor dynamically regulates the mRNA stabilome in rheumatoid arthritis fibroblast-like synoviocytes.PLoS One.2017;12(7):e0179762.
Systemic Lupus Erythematosus (SLE)
- Howlader MJ, Ambler WG, Chalasani MLS, Rathod A, Seltzer ES, Sim JH, Shin J, Schwartz N, Shipman WD 3rd, Dasoveanu DC, Carballo CB, Sevim E, Siddique S, Chinenov Y, Rodeo SA, Erkan D, Kataru RP, Mehrara BJ, Lu TT. Lymphatic dysfunction in lupus contributes to cutaneous photosensitivity and lymph node B cell responses. J Clin Invest. 2025 Jun 16;135(12).
- Li TM, Zyulina V, Seltzer ES, Dacic M, Chinenov Y, Daamen AR, Veiga KR, Schwartz N, Oliver DJ, Cabahug-Zuckerman P, Lora J, Liu Y, Shipman WD, Ambler WG, Taber SF, Onel KB, Zippin JH, Rashighi M, Krueger JG, Anandasabapathy N, Rogatsky I, Jabbari A, Blobel CP, Lipsky PE, Lu TT. The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus. 2024 Jun 11;13.
- Ricker E, Manni M, Flores-Castro D, Jenkins D, Gupta S, Rivera-Correa J, Meng W, Rosenfeld AM, Pannellini T, Bachu M, Chinenov Y, Sculco PK, Jessberger R, Prak ETL, Pernis AB. Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice. Nat Commun. 2021 Aug 10;12(1):4813.
- Manni M, Gupta S, Ricker E, Chinenov Y, Park SH, Shi M, Pannellini T, Jessberger R, Ivashkiv LB, Pernis AB. Regulation of age-associated B cells by IRF5 in systemic autoimmunity.Nat Immunol.2018 Feb 26.
- Yi W, Gupta S, Ricker E, Manni M, Jessberger R, et al. The mTORC1-4E-BP-eIF4E axis controls de novo Bcl6 protein synthesis in T cells and systemic autoimmunity.Nat Commun.2017 Aug 15;8(1):254.
- Rozo C, Chinenov Y, Maharaj RK, Gupta S, Leuenberger L, et al. Targeting the RhoA ROCK pathway to reverse T-cell dysfunction in SLE.Ann Rheum Dis.2017 Apr;76(4):740-747.
Translation/Precision Medicine
- Chen X, Shibu G, Sokolsky BA, Soussana TN, Fisher L, Deochand DK, Dacic M, Mantel I, Ramirez DC, Bell RD, Zhang T, Donlin LT, Goodman SM, Gray NS, Chinenov Y, Fisher RP, Rogatsky I. Disrupting the RNA polymerase II transcription cycle through CDK7 inhibition ameliorates inflammatory arthritis. Sci Transl Med. 2024 Nov 20;16(774):
- Çakan E, Ah Kioon MD, Garcia-Carmona Y, Glauzy S, Oliver D, Yamakawa N, Vega Loza A, Du Y, Schickel JN, Boeckers JM, Yang C, Baldo A, Ivashkiv LB, Young RM, Staudt LM, Moody KL, Nündel K, Marshak-Rothstein A, van der Made CI, Hoischen A, Hayward A, Rossato M, Radstake TRDJ, Cunningham-Rundles C, Ryu C, Herzog EL, Barrat FJ, Meffre E. TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance. J Exp Med. 2023 Dec 4;220(12):e20230944.
- Kirksey MA, Lessard SG, Khan M, Birch GA, Oliver D, Singh P, Rotundo V, Sideris A; TKAF Consortium; Gonzalez Della Valle A, Parks ML, Sculco PK, Otero M. Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study. Sci Rep. 2022 Jul 25;12(1):12651.
- Zahir H, Dehghani B, Yuan X, Chinenov Y, Kim C, Burge A, Bandhari R, Nemirov D, Fava P, Moley P, Potter H, Nguyen J, Halpern B, Donlin L, Ivashkiv L, Rodeo S, Otero M. In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis. Sci Rep. 2021 Jun 1;11(1):11493.
- Xia Y, Sokhi UK, Bell RD, Pannellini T, Turajane K, Niu Y, Frye L, Chao M, Ayturk U, Otero M, Bostrom M, Oliver D, Yang X, Ivashkiv LB. Immune and repair responses in joint tissues and lymph nodes after knee arthroplasty surgery in mice. J Bone Miner Res. 2021 Sep;36(9):1765-1780.
- Kuo D, Ding J, Cohn IS, Zhang F, Wei K, Rao DA, Rozo C, Sokhi UK, Shanaj S, Oliver DJ, Echeverria AP, DiCarlo EF, Brenner MB, Bykerk VP, Goodman SM, Raychaudhuri S, Rätsch G, Ivashkiv LB, Donlin LT. HBEGF+macrophages in rheumatoid arthritis induce fibroblast invasiveness. Sci Transl Med. 2019 May 8;11(491):eaau8587.
- Giannopoulou EG, Elemento O, Ivashkiv LB. Use of RNA sequencing to evaluate rheumatic disease patients.Arthritis Res Ther.2015 Jul 1;17:167.
- Rogatsky I, Adelman K. Preparing the first responders: building the inflammatory transcriptome from the ground up.Mol Cell.2014 Apr 24;54(2):245-54.
- Ah Kioon MD, Tripodo C, Fernandez D, Kirou KA, Spiera RF, Crow MK, Gordon JK, Barrat FJ. Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8.Science Translational Medicine.2018;10(423).
- Laura T. Donlin*, Deepak A. Rao*, Kevin Wei, Kamil Slowikowski, Mandy J. McGeachy, Jason D. Turner, Nida Meednu, Fumitaka Mizoguchi, Maria Gutierrez-Arcelus, David J. Lieb, Joshua Keegan, Kaylin Muskat, Joshua Hillman, Cristina Rozo, Edd Ricker, Thomas M. Eisenhaure, Shuqiang Li, Edward P. Browne, Adam Chicoine, Danielle Sutherby, Akiko Noma, Accelerating Medicines Partnership: RA/SLE Network, Chad Nusbaum, Stephen Kelly, Alessandra B. Pernis, Lionel B. Ivashkiv, Susan M. Goodman, William H. Robinson, Paul J. Utz, James A. Lederer, Ellen M. Gravallese, Brendan F. Boyce, Nir Hacohen, Costantino Pitzalis, Peter K. Gregersen, Gary S. Firestein, Soumya Raychaudhuri, Larry W. Moreland, V. Michael Holers, Vivian P. Bykerk, Andrew Filer, David L. Boyle, Michael B. Brenner, Jennifer H. Anolik. High dimensional analyses of cells dissociated from cryopreserved synovial tissue.CSHL BioRxiv.
Biological Mechanisms
- Rivera-Correa J, Gupta S, Ricker E, Flores-Castro D, Jenkins D, Vulcano S, Phalke SP, Pannellini T, Miele MM, Li Z, Zamponi N, Kim YB, Chinenov Y, Giannopoulou E, Cerchietti L, Pernis AB. ROCK1 promotes B cell differentiation and proteostasis under stress through the heme-regulated proteins, BACH2 and HRI. JCI Insight. 2025 Feb 4;10(5).
- Deochand DK, Dacic M, Bale MJ, Daman AW, Chaudhary V, Josefowicz SZ, Oliver D, Chinenov Y, Rogatsky I. Mechanisms of epigenomic and functional convergence between glucocorticoid- and IL4-driven macrophage programming. Nat Commun. 2024 Oct 18;15(1):9000
- Yuan R, Ma Y, Yang C, Li L. Editorial: Plasticity of monocytes/macrophages: phenotypic changes during disease progression. Front Immunol. 2023 Nov 13;14:1328382. doi: 10.3389/fimmu.2023.1328382. PMID: 38022604; PMCID: PMC10679671.
- Yang C, Yuan R, Brauner C, Du Y, Ah Kioon MD, Barrat FJ, Ivashkiv LB. Dichotomous roles of RIPK3 in regulating the IFN response and NLRP3 inflammasome in human monocytes. J Leukoc Biol. 2023 Nov 24;114(6):615-629.
- Yang C, Bachu M, Du Y, Brauner C, Yuan R, Ah Kioon MD, Chesi G, Barrat FJ, Ivashkiv LB. CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes. Nat Commun. 2022 Jun 14;13(1):3426. doi: 10.1038/s41467-022-31132-7. PMID: 35701499; PMCID: PMC9195402.
- Du Y, Ah Kioon MD, Laurent P, Chaudhary V, Pierides M, Yang C, Oliver D, Ivashkiv LB, Barrat FJ. Chemokines form nanoparticles with DNA and can superinduce TLR-driven immune inflammation. J Exp Med. 2022 Jul 4;219(7):e20212142.
- Gasparian A, Aksenova M, Oliver D, Levina E, Doran R, Lucius M, Piroli G, Oleinik N, Ogretmen B, Mythreye K, Frizzell N, Broude E, Wyatt MD, Shtutman M. Depletion of COPI in cancer cells: the role of reactive oxygen species in the induction of lipid accumulation, noncanonical lipophagy and apoptosis. Mol Biol Cell. 2022 Dec 1;33(14):ar135.
- Mimouna S, Rollins DA, Shibu G, Tharmalingam B, Deochand DK, Chen X, Oliver D, Chinenov Y, Rogatsky I. Transcription cofactor GRIP1 differentially affects myeloid cell-driven neuroinflammation and response to IFN-β therapy. J Exp Med. 2021 Jan 4;218(1).
- Ricker E, Chinenov Y, Pannellini T, Flores-Castro D, Ye C, Gupta S, Manni M, Liao JK, Pernis AB. Serine-threonine kinase ROCK2 regulates germinal center B cell positioning and cholesterol biosynthesis. J Clin Invest. 2020 Jul 1;130(7):3654-3670
- Yu L, Zhang B, Deochand D, Sacta MA, Coppo M, Shang Y, Guo Z, Zeng X, Rollins DA, Tharmalingam B, Li R, Chinenov Y, Rogatsky I, Hu X. Negative elongation factor complex enables macrophage inflammatory responses by controlling anti-inflammatory gene expression. Nat Commun. 2020 May 8;11(1):2286
- Kusnadi A, Park SH, Yuan R, Pannellini T, Giannopoulou E, Oliver D, Lu T, Park-Min KH, Ivashkiv LB. The Cytokine TNF Promotes Transcription Factor SREBP Activity and Binding to Inflammatory Genes to Activate Macrophages and Limit Tissue Repair. Immunity. 2019 Aug 20;51(2):241-257.e9. doi: 10.1016/j.immuni.2019.06.005. Epub 2019 Jul 11. PMID: 31303399; PMCID: PMC6709581.
- Gupte R, Muse GW, Chinenov Y, Adelman K, and Rogatsky I. Glucocorticoid receptor represses proinflammatory genes at distinct steps of the transcription cycle.2013 Sep 3;110(36):14616-21.
- Sacta MA, Tharmalingam B, Coppo M, Rollins DA, Deochand DK, Benjamin B, Yu L, Zhang B, Hu X, Li R, Chinenov Y, Rogatsky I. Gene-specific mechanisms direct glucocorticoid-receptor-driven repression of inflammatory response genes in macrophages.2018 Feb 9;7. pii: e34864.
- Rollins DA, Kharlyngdoh JB, Coppo M, Tharmalingam B, Mimouna S, et al. Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator functions of transcriptional cofactor GRIP1 in macrophages.Nat Commun.2017 Nov 23;8(1):1739.
- Park SH, Kang K, Giannopoulou E, Qiao Y, Kang K, et al. Type I interferons and the cytokine TNF cooperatively reprogram the macrophage epigenome to promote inflammatory activation.Nat Immunol.2017 Oct;18(10):1104-1116.
- Kang K, Park SH, Chen J, Qiao Y, Giannopoulou E, et al. Interferon-γ Represses M2 Gene Expression in Human Macrophages by Disassembling Enhancers Bound by the Transcription Factor MAF.2017 Aug 15;47(2):235-250.e4.
- Qiao Y, Kang K, Giannopoulou E, Fang C, Ivashkiv LB. IFN-γ Induces Histone 3 Lysine 27 Trimethylation in a Small Subset of Promoters to Stably Silence Gene Expression in Human Macrophages.Cell Rep.2016 Sep 20;16(12):3121-3129.
- Coppo M, Chinenov Y, Sacta MA, Rogatsky I. The transcriptional coregulator GRIP1 controls macrophage polarization and metabolic homeostasis.Nat Commun.2016 Jul 28;7:12254.
- Su X, Yu Y, Zhong Y, Giannopoulou EG, Hu X, et al. Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation.Nat Immunol.2015 Aug;16(8):838-849.
- Donlin LT, Jayatilleke A, Giannopoulou EG, Kalliolias GD, Ivashkiv LB. Modulation of TNF-induced macrophage polarization by synovial fibroblasts.J Immunol.2014 Sep 1;193(5):2373-83.
- Qiao Y, Giannopoulou EG, Chan CH, Park SH, Gong S, et al. Synergistic activation of inflammatory cytokine genes by interferon-γ-induced chromatin remodeling and toll-like receptor signaling.2013 Sep 19;39(3):454-69.
- Sokhi UK, Liber MP, Frye L, Park S, Kang K, Pannellini T, Zhao B, Norinsky R, Ivashkiv LB, Gong S. Dissection and function of autoimmunity-associated TNFAIP3 (A20) gene enhancers in humanized mouse models.Nature Communications.2018;9(1):658.
- Barrat FJ, Elkon KB, Fitzgerald KA. Importance of Nucleic Acid Recognition in Inflammation and Autoimmunity.Annual Review of Medicine.2016;67:323-36.
Bone & Tendons
- Inoue K, Qin Y, Xia Y, Han J, Yuan R, Sun J, Xu R, Jiang JX, Greenblatt MB, Zhao B. Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis, and bone mass. 2023 Feb 13;12:e82118. doi: 10.7554/eLife.82118. PMID: 36779851; PMCID: PMC10005769.
- Disser NP, Piacentini AN, De Micheli AJ, Schonk MM, Yao VJH, Deng XH, Oliver DJ, Rodeo SA. Achilles Tendons Display Region-Specific Transcriptomic Signatures Associated With Distinct Mechanical Properties. Am J Sports Med. 2022 Dec;50(14):3866-3874.
- Turajane K, Ji G, Chinenov Y, Chao M, Ayturk U, Suhardi VJ, Greenblatt MB, Ivashkiv LB, Bostrom MP, Yang X. RNA-seq Analysis of Peri-Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice. JBMR Plus. 2021 Nov;5(11):e10535.
- Fujii T, Murata K, Mun SH, Bae S, Lee YJ, Pannellini T, Kang K, Oliver D, Park-Min KH, Ivashkiv LB. MEF2C regulates osteoclastogenesis and pathologic bone resorption via c-FOS. Bone Res. 2021 Jan 11;9(1):4.
- De Micheli AJ, Swanson JB, Disser NP, Martinez LM, Walker NR, Oliver DJ, Cosgrove BD, Mendias CL. Single-cell transcriptomic analysis identifies extensive heterogeneity in the cellular composition of mouse Achilles tendons. Am J Physiol Cell Physiol. 2020 Nov 1;319(5):C885-C894.
- Disser NP, Ghahramani GC, Swanson JB, Wada S, Chao ML, Rodeo SA, Oliver DJ, Mendias CL. Widespread diversity in the transcriptomes of functionally divergent limb tendons. J Physiol. 2020 Apr;598(8):1537-1550.
- Sarver DC, Sugg KB, Talarek JR, Swanson JB, Oliver DJ, Hinken AC, Kramer HF, Mendias CL. Prostaglandin D2signaling is not involved in the recovery of rat hind limb tendons from injury. Physiol Rep. 2019 Nov;7(22):e14289.
- Murata K, Fang C, Terao C, Giannopoulou EG, Lee YJ, et al. Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis.2017 Jul 18;47(1):66-79.e5.
- Bae S, Lee MJ, Mun SH, Giannopoulou EG, Yong-Gonzalez V, et al. MYC-dependent oxidative metabolism regulates osteoclastogenesis via nuclear receptor ERRα.J Clin Invest. 2017 Jun 30;127(7):2555-2568.
- Binder N, Miller C, Yoshida M, Inoue K, Nakano S, et al. Def6 Restrains Osteoclastogenesis and Inflammatory Bone Resorption.J Immunol. 2017 May 1;198(9):3436-3447.
- Park-Min KH. Epigenetic regulation of bone cells.Connect Tissue Res.2017 Jan;58(1):76-89.
- Miller CH, Smith SM, Elguindy M, Zhang T, Xiang JZ, et al. RBP-J-Regulated miR-182 Promotes TNF-α-Induced Osteoclastogenesis.J Immunol. 2016 Jun 15;196(12):4977-86.
- Zheng HF, el. al. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. 2015;526(7571):112-7.
Bioinformatics
- Oliver D (2025). CRAN pkgGraphR: Graph the Relationship Between Functions in an R Package. R package version 0.3.1, https://gitlab.com/doliv071/pkggraphr.
- Sacta MA, Chinenov Y, Rogatsky I. Glucocorticoid Signaling: An Update from a Genomic Perspective.Annu Rev Physiol.2016;78:155-80.
- Chinenov Y, Coppo M, Gupte R, Sacta MA, Rogatsky I. Glucocorticoid receptor coordinates transcription factor-dominated regulatory network in macrophages.BMC Genomics.2014 Aug 6;15:656.
Arthritis and Tissue Degeneration Program
- A single cell atlas of the mouse Achilles tendon (September 2019): An interactive map and visualization of gene expressions by cell type.
- Comparative tendon transcriptional atlas (November 2019): An interactive atlas of differential gene expression in limb tendons.
Funding Sources
The David Z. Rosensweig Genomics Research Center was founded with generous support provided by The Tow Foundation. This support has been leveraged to obtain additional funding from the National Institutes of Health, Department of Defense and various foundations and philanthropic organizations.
Primary Supporter
Additional Research Funding
- National Institutes of Health
- Department of Defense
- Lupus Research Alliance
- Arthritis National Research Foundation
- Rheumatology Research Foundation
- Feinstein Medical Foundation
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