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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.

Bioinformatics Core

Yurii Chinenov, PhD
David Oliver, PhD
Ruoxi Yuan, PhD

Collaborators

Ugur Ayturk, PhD
Franck Barrat, PhD
Laura Donlin, PhD
Lionel B. Ivashkiv, MD
Rheumatologist
Upper East Side
Miguel Otero, PhD
Kyung Hyun Park-Min, PhD
Alessandra Pernis, MD
Inez Rogatsky, PhD
Jane E. Salmon, MD
Rheumatologist
Upper East Side
Baohong Zhao, PhD

Autoimmunity

Rheumatoid Arthritis (RA)

 

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

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

 

Arthritis and Tissue Degeneration Program

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

Tow Foundation Logo

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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