Lionel B. Ivashkiv, MD

Dr. Ivashkiv is Chief Scientific Officer at Hospital for Special Surgery and Professor of Medicine and Immunology at Weill Cornell Medicine. He holds the Richard L. Menschel Research Chair and is the David H. Koch Chair in Arthritis and Tissue Degeneration at HSS. Dr. Ivashkiv is also an Attending Physician and Director of the David Z. Rosensweig Genomics Research Center at HSS.

As Chief Scientific Officer, Dr. Ivashkiv oversees the Hospital’s clinical, translational, and basic research programs, which encompass over 200 scientists and staff working to identify causes of and new treatments for orthopaedic and rheumatic conditions such as arthritis, bone and soft tissue injuries, autoimmune diseases, and musculoskeletal pain and deformities. Long-term research goals include expanding translational research, building multidisciplinary teams to study patients to answer key clinical questions, enhancing clinical research; and broadening the scope and impact of basic science on musculoskeletal disorders, with a focus on tissue repair, improving surgical outcomes, autoimmunity and inflammation, aging of musculoskeletal tissues, genomics, new treatments, and precision medicine.

Dr. Ivashkiv’s laboratory investigates the pathogenic mechanisms of cytokines in inflammatory and musculoskeletal conditions such as rheumatoid arthritis, osteolysis and orthopaedic implant loosening/failure, and systemic lupus erythematosus. He is interested in how cytokines and inflammatory factors regulate the activation and function of innate immune and stromal cells, with a focus on macrophages, osteoclasts, and synovial fibroblasts. Macrophages play key roles in inflammation and tissue damage/repair, osteoclasts destroy bone, and synovial fibroblasts contribute to arthritis. Cytokines are key regulators of these cells and of immune responses important in inflammatory and musculoskeletal diseases. Cytokines determine the severity of inflammation and the extent of associated tissue damage and/or repair. The Ivashkiv laboratory studies cytokine signaling, mechanisms of cytokine production, and epigenetic regulation of inflammatory gene expression to discover new mechanisms and therapeutic targets for inflammatory and musculoskeletal diseases.

We have worked extensively on signal transduction crosstalk between cytokines that activate the Jak-STAT signaling pathway, such as IFN-g, IFN-a and IL-10, and inflammatory activators of macrophages such as Toll-like receptor ligands and TNF. We have connected these signaling pathways with downstream chromatin-mediated and epigenetic mechanisms that regulate gene expression and inflammatory cell phenotypes. This work uses primary human cells relevant for disease pathogenesis, disease models, and includes genome-wide approaches to study gene expression, epigenomic mechanisms, and identification and characterization of enhancers.

We are currently studying how cytokines such as IFNs and TNF reprogram macrophage responses to the environment by altering transcription factor networks, chromatin states, cell metabolism, and the epigenomic landscape of enhancers. Such reprogramming results in macrophages that are hyper-responsive (‘primed’) or desensitized (‘tolerized’) to inflammatory challenges. Understanding of underlying mechanisms will enable novel therapeutic approaches to selectively modulate expression of key inflammatory genes such as TNF and IL6 to suppress inflammatory diseases. Additional areas of interest include mechanisms that sustain inflammatory responses in synovial fibroblasts, functional coupling between macrophages and fibroblasts, transcription factor networks that control osteoclast differentiation and pathologic bone resorption, and using a transgenic approach that couples bacterial artificial chromosomes (BACs) and CRISPR-Cas9 genome editing to study the regulation of human autoimmunity-associated genes such as A20/TNFAIP3. We have become involved in multidisciplinary teams that study flares and resistance to therapy in rheumatoid arthritis, osteolysis and aseptic loosening of orthopaedic implants, stiffness and pain after total knee replacement, and spine degeneration and pain.

The laboratory integrates basic science investigation of signaling and epigenetic mechanisms with translational research using disease models and analysis of human disease samples with genome wide approaches such as RNA-seq, ChIP-seq, and ATAC-seq. We are incorporating a precision medicine approach to identify disease mechanisms and the best therapies for individual patients. Our long term goals are to identify signaling and epigenetic mechanisms that can be targeted by new therapies for inflammatory and musculoskeletal diseases, including biological approaches to improve surgical outcomes.

Appointments

Chief Scientific Officer, Hospital for Special Surgery
Richard L. Menschel Research Chair

David H. Koch Chair in Arthritis and Tissue Degeneration
Professor, Medicine and Immunology, Weill Cornell Medicine
Director, HSS Genomics Center
Attending Physician, Hospital for Special Surgery
 

 

Specialty

Special Expertise

Rheumatoid arthritis
Inflammatory bone diseases

Awards

Elected Member, Association of American Physicians, 2015
Scientific ‘Guru’, NIAMS, NIH, 2014
Elected Member, Henry Kunkel Society for Human Immunology, 2004
Elected Member, American Society for Clinical Investigation, 2001
Jack Friedman Young Investigator Prize, Weill Cornell Medical College, 1995
Young Scholar Award, Arthritis Foundation, New York Chapter, 1995
Arthritis Investigator Award, 1993
Clinical Investigator Award, 1990
Soma Weiss Award, Harvard Medical School, 1984

Affiliations

American College of Rheumatology
Orthopaedic Research Society
International Cytokine and Interferon Society
American Association of Immunologists

Insurances Accepted


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Education

MD, Harvard Medical School, Boston, Massachusetts

Residency

New York University - Bellevue Hospital, New York

Fellowship

Harvard Medical School - Brigham and Women's Hospital

Certification

Rheumatology
Internal Medicine

State Licensure

New York

Lionel B. Ivashkiv, MD has contributed to the following educational materials:

For Professionals - on HSS.edu

Selected Publications

Qiao, Y., E. G. Giannopoulou, C. H. Chan, S.-H. Park, S. Gong, J. Chen, X. Hu, O. Elemento and L. B. Ivashkiv. 2013. Synergistic activation of inflammatory cytokine genes by Interferon-g-induced chromatin remodeling and Toll-like receptor signaling. Immunity 19:454-469. PMC3857147

Park-Min, K. H., E. Lim, M. J. Lee, S. H. Park, E. Giannopoulou, A. Yarilina, M. van der Meulen, B. Zhao, N. Smithers, J. Witherington, K. Lee, P. P. Tak, R. K. Prinjha, and L. B. Ivashkiv. 2014. Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation. Nature Communications 5: 5418. PMC4249944

Su, X., Y. Yu, Y. Zhong, E. G. Giannopoulou, X. Hu, H. Liu, J. R. Cross, G. Rätsch, C. M. Rice and L. B. Ivashkiv. 2015. IFN-gamma Regulates mTORC1, cellular metabolism and mRNA translation to potentiate inflammatory macrophage activation. Nature Immunology 16:838-849. PMC4509841.

L. B. Ivashkiv  and L. T. Donlin. 2014.Regulation of type I IFN responses. Nature Rev Immunol 14:36-49. PMC4084561

 

For more publications, please see the PubMed listing.

Research Description

Dr. Ivashkiv’s laboratory investigates the pathogenic mechanisms of cytokines in inflammatory and musculoskeletal conditions such as rheumatoid arthritis, osteolysis and orthopaedic implant loosening/failure, and systemic lupus erythematosus. He is interested in how cytokines and inflammatory factors regulate the activation and function of innate immune and stromal cells, with a focus on macrophages, osteoclasts, and synovial fibroblasts. Macrophages play key roles in inflammation and tissue damage/repair, osteoclasts destroy bone, and synovial fibroblasts contribute to arthritis. Cytokines are key regulators of these cells and of immune responses important in inflammatory and musculoskeletal diseases. Cytokines determine the severity of inflammation and the extent of associated tissue damage and/or repair. The Ivashkiv laboratory studies cytokine signaling, mechanisms of cytokine production, and epigenetic regulation of inflammatory gene expression to discover new mechanisms and therapeutic targets for inflammatory and musculoskeletal diseases.

We have worked extensively on signal transduction crosstalk between cytokines that activate the Jak-STAT signaling pathway, such as IFN-g, IFN-a and IL-10, and inflammatory activators of macrophages such as Toll-like receptor ligands and TNF. We have connected these signaling pathways with downstream chromatin-mediated and epigenetic mechanisms that regulate gene expression and inflammatory cell phenotypes. This work uses primary human cells relevant for disease pathogenesis, disease models, and includes genome-wide approaches to study gene expression, epigenomic mechanisms, and identification and characterization of enhancers.

We are currently studying how cytokines such as IFNs and TNF reprogram macrophage responses to the environment by altering transcription factor networks, chromatin states, cell metabolism, and the epigenomic landscape of enhancers. Such reprogramming results in macrophages that are hyper-responsive (‘primed’) or desensitized (‘tolerized’) to inflammatory challenges. Understanding of underlying mechanisms will enable novel therapeutic approaches to selectively modulate expression of key inflammatory genes such as TNF and IL6 to suppress inflammatory diseases. Additional areas of interest include mechanisms that sustain inflammatory responses in synovial fibroblasts, functional coupling between macrophages and fibroblasts, transcription factor networks that control osteoclast differentiation and pathologic bone resorption, and using a transgenic approach that couples bacterial artificial chromosomes (BACs) and CRISPR-Cas9 genome editing to study the regulation of human autoimmunity-associated genes such as A20/TNFAIP3. We have become involved in multidisciplinary teams that study flares and resistance to therapy in rheumatoid arthritis, osteolysis and aseptic loosening of orthopaedic implants, stiffness and pain after total knee replacement, and spine degeneration and pain.

The laboratory integrates basic science investigation of signaling and epigenetic mechanisms with translational research using disease models and analysis of human disease samples with genome wide approaches such as RNA-seq, ChIP-seq, and ATAC-seq. We are incorporating a precision medicine approach to identify disease mechanisms and the best therapies for individual patients. Our long term goals are to identify signaling and epigenetic mechanisms that can be targeted by new therapies for inflammatory and musculoskeletal diseases, including biological approaches to improve surgical outcomes.

Clinical Trials

 
Dr. Lionel Ivashkiv, Rheumatologist, Internist

Contact Information

Office Locations

Hospital for Special Surgery
535 East 70th Street
New York, NY 10021

Tel: 212.606.1653
Fax: 212.606.1170

Mailing Address

Hospital for Special Surgery
535 East 70th Street
New York, New York 10021

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