An official website of the United States government
          Here’s how you know
        Here’s how you know**Official websites use .gov**A
              **.gov** website belongs to an official government
              organization in the United States.
        **Secure .gov websites use HTTPS**A
              **lock** (
              Locked padlock icon) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.
 Top Utility Nav
        
        
        Asian-Language Resources
        
        Portal en español


Site search Mega Menu
  

        

        Home
                  Health Topics
                                      
    
  Health Topics

    Arthritis and Rheumatic Diseases
          
    Muscle and Bone Diseases
          
    Skin Diseases
          
    All Diseases and Conditions
          
    Publication Catalog
                  Grants & Funding
                                      
    
  Grants & Funding

    Current Funding Opportunities
          
    Supported Scientific Programs
          
    NIAMS-Supported Programs
          
    Applying for a Grant
          
    NIH Policies and Guidance
          
    Peer Review and Grants Administration Resources
          
    Types of Funding Mechanisms (Activity Codes)
                  Labs @ NIAMS
                                      
    
  Labs @ NIAMS

    NIAMS Labs and Core Facilities
          
    Research Faculty
          
    Research Areas
          
    NIAMS Scientific Advances
          
    Training and Career Development
                  Clinical Trials
                                      
    
  Clinical Trials
      
            For Principal Investigators

    Clinical Trial Policies, Guidelines, and Templates
          
    Conducting Clinical Trials
          
    Register with ClinicalTrials.gov

For Patients

What is a Clinical Trial?
	Clinical Trials at NIAMS
	Clinical Trials in the Spotlight
                  News & Events
                                      
    
  Newsroom

    All NIAMS News
          
    NIAMS Newsletters
          
    Meetings & Events
                  About NIAMS
                                      
    
  About NIAMS

    Director's Page
          
    NIAMS Organization
          
    Strategic Plan Fiscal Years 2020-2024
          
    Staff Directory
          
    NIAMS Budget
          
    Partnerships
          
    Contact NIAMS
                  Community Outreach
                                      
    
  Community Outreach

    Bone Health
          
    Joint Health
          
    Muscle, Tendon, and Ligament Health
          
    Skin Health
          
    Health Information For Kids And Young Adults
          
    Health Information For Older Adults/Seniors
          
    Printable Materials for Community Events
          
    Resources in Other Languages
          
    Annual Health Observances
          
    Social Media Resources Breadcrumb
    Home
          About NIAMS
          Michael J. Ombrello, M.D.





Michael J. Ombrello, M.D.


Investigator
    Chief, Translational Genetics and Genomics Section Image
              Michael J. Ombrello, M.D. 
            Contact Information

                                                  301-435-4037
                
                                                9000 Rockville Pike
                  
            10 Center Drive
      
                  
            Building 10, Room 13C103A
      
                                   Bethesda MD 20892
                
                                                ombrellomj@mail.nih.gov 
                                          Media Resources
                                  
            High Resolution Image 
                Summary
          Michael Ombrello, M.D., is an adult and pediatric rheumatologist. He completed his undergraduate degree (1997) and medical degree (2002) at Saint Louis University. Upon completing a Combined Adult and Pediatric Rheumatology Fellowship, he was awarded the 2010 Distinguished Fellow Award from the American College of Rheumatology. Dr. Ombrello was an inaugural NIAMS Henry Metzger Scholar in Translational Research. He completed an additional two-year postdoctoral fellowship in the Inflammatory Disease Section of the National Human Genome Research Institute.

Dr. Ombrello is currently a Tenure-Track Investigator at the NIAMS. His research program focuses on discovering genetic causes of rare inflammatory diseases in humans, translating those discoveries into an improved understanding of inflammatory pathophysiology, and identifying new therapeutic targets for treating inflammatory diseases.

Over the past decade, Dr. Ombrello has been a pioneer in Still’s disease genomics, leading the investigations of the International Childhood Genetics (INCHARGE) Consortium. His studies unexpectedly implicated adaptive immune mechanisms and unambiguously demonstrated that the unique genetic architecture of Still’s disease distinguishes it from the other forms of childhood arthritis. His group has also identified the first genetic biomarkers that may guide the future treatment of Still’s disease. These include one that identifies non-responders to a commonly used treatment and another that strongly predicts which subjects will develop a potentially fatal hypersensitivity reaction to a group of widely used therapies.

In addition to studying Still’s disease, Dr. Ombrello described the first disease-causing mutations of *PLCG2*in humans. His group continues to engage in clinical and translational investigations of immune-mediated disease caused by *PLCG2*variation.

Dr. Ombrello has received numerous NIH honors and awards, most notably the NIH Fellows Award for Research Excellence, Merit Awards from NIAMS and NIAID, and the NIH Director’s Award.

Dr. Ombrello is firmly committed to mentoring and training the next generation of investigators within and beyond the NIH community. He served a 4-year term on the American College of Rheumatology’s Early Career Investigator subcommittee, during which he worked to develop and deliver career development content to early career rheumatologist-scientists. However, his commitment to mentorship is best reflected by the success of his NIAMS lab members, whose research accomplishments have also been recognized with many local and national awards. These include the Distinguished Fellow Award from the American College of Rheumatology, multiple recipients of the NIH Fellows Award for Research Excellence, and numerous “Best Presentation” awards from national and international scientific meetings.
        
                  Research Statement
          
            Autoinflammatory diseases are caused by inappropriate or excessive activation of innate immune pathways. When unchecked, this excessive inflammation can result in tissue damage, organ failure, and death. The Translational Genetics and Genomics Section (TGGS) aims to identify mechanisms of autoinflammatory pathophysiology and translate these insights into new or improved therapeutic approaches to treat inflammatory diseases.Systemic autoinflammatory diseases are rare, familial inflammatory conditions caused by mutations in individual genes. Other autoinflammatory conditions do not demonstrate familial inheritance, instead showing a more complicated, polygenic inheritance. Still's disease, which includes systemic juvenile idiopathic arthritis (sJIA) in children and adult-onset Still's disease (AOSD) in adults, is one such condition.Still’s disease is a severe, systemic inflammatory condition that is  is characterized by periods of prolonged, unexplained fever and chronic arthritis, together with inflammation of the skin and organs. The complications of Still’s disease can be life-threatening. They include macrophage activation syndrome (MAS), a cytokine storm syndrome, and an emergent form of interstitial lung disease strongly associated with the *DR15* ancestral HLA haplotype, which develops in the context of an atypical hypersensitivity reaction to a group of cytokine inhibitors.The TGGS was established in 2013 to identify genetic factors that contribute to the development of Still’s disease and other genetically complex autoinflammatory diseases. In its earliest days, members of the TGGS performed the first genomic studies of Still’s disease, which yielded various new and unexpected insights. In 2018, the TGGS established a natural history protocol at the NIH Clinical Center, which provided an infrastructure for integrated genomic and immunologic investigations of children and adults with Still’s disease and other genetically complex forms of autoinflammation.**Current projects include:**Family-based genomics of Still’s disease.Molecular classification of children and adults with refractory forms of Still’s disease.Genomics of Still’s disease-associated lung disease.Pharmacogenomics of Still’s disease.Detailed clinical and functional characterization of *PLCG2*-associated immune dysregulation. 

            Scientific Publications
              PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.

    Baysac K, Sun G, Nakano H, Schmitz EG, Cruz AC, Fisher C, Bailey AC, PLCG2-Immune Dysregulation Working Group, Mace E, Milner JD, Ombrello MJ
        

                    J Allergy Clin Immunol.
        
                    2024 Jan;
        
                    153(1).
        
                    doi: 10.1016/j.jaci.2023.08.036
                            PMID: 37769878
  A Cysteine Variant at an Allosteric Site Alters MIF Dynamics and Biological Function in Homo- and Heterotrimeric Assemblies.

    Skeens E, Pantouris G, Shah D, Manjula R, Ombrello MJ, Maluf NK, Bhandari V, Lisi GP, Lolis EJ
        

                    Front Mol Biosci.
        
                    2022;
        
                    9().
        
                    doi: 10.3389/fmolb.2022.783669
                            PMID: 35252348
  Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles.

    Saper VE, Ombrello MJ, Tremoulet AH, Montero-Martin G, Prahalad S, Canna S, Shimizu C, Deutsch G, Tan SY, Remmers EF, Monos D, Hahn T, Phadke OK, Cassidy E, Ferguson I, Mallajosyula V, Xu J, Rosa Duque JS, Chua GT, Ghosh D, Szymanski AM, Rubin D, Burns JC, Tian L, Fernandez-Vina MA, Mellins ED, Hollenbach JA, Drug Hypersensitivity Consortium, INCHARGE Consortium
        

                    Ann Rheum Dis.
        
                    2022 Mar;
        
                    81(3).
        
                    doi: 10.1136/annrheumdis-2021-220578
                            PMID: 34789453
  IL1RN Variation Influences Both Disease Susceptibility and Response to Recombinant Human Interleukin-1 Receptor Antagonist Therapy in Systemic Juvenile Idiopathic Arthritis.

    Arthur VL, Shuldiner E, Remmers EF, Hinks A, Grom AA, Foell D, Martini A, Gattorno M, Özen S, Prahalad S, Zeft AS, Bohnsack JF, Ilowite NT, Mellins ED, Russo R, Len C, Oliveira S, Yeung RSM, Rosenberg AM, Wedderburn LR, Anton J, Haas JP, Rösen-Wolff A, Minden K, Szymanski AM, INCHARGE Consortium, Thomson W, Kastner DL, Woo P, Ombrello MJ
        

                    Arthritis Rheumatol.
        
                    2018 Aug;
        
                    70(8).
        
                    doi: 10.1002/art.40498
                            PMID: 29609200
  Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications.

    Ombrello MJ, Arthur VL, Remmers EF, Hinks A, Tachmazidou I, Grom AA, Foell D, Martini A, Gattorno M, Özen S, Prahalad S, Zeft AS, Bohnsack JF, Ilowite NT, Mellins ED, Russo R, Len C, Hilario MO, Oliveira S, Yeung RS, Rosenberg AM, Wedderburn LR, Anton J, Haas JP, Rosen-Wolff A, Minden K, Tenbrock K, Demirkaya E, Cobb J, Baskin E, Signa S, Shuldiner E, Duerr RH, Achkar JP, Kamboh MI, Kaufman KM, Kottyan LC, Pinto D, Scherer SW, Alarcón-Riquelme ME, Docampo E, Estivill X, Gül A, British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group, Inception Cohort of Newly Diagnosed Patients with Juvenile Idiopathic Arthritis (ICON-JIA) Study Group, Childhood Arthritis Prospective Study (CAPS) Group, Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators, Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group, Biologically Based Outcome Predictors in JIA (BBOP) Group, Langefeld CD, Thompson S, Zeggini E, Kastner DL, Woo P, Thomson W
        

                    Ann Rheum Dis.
        
                    2017 May;
        
                    76(5).
        
                    doi: 10.1136/annrheumdis-2016-210324
                            PMID: 27927641
  HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis.

    Ombrello MJ, Remmers EF, Tachmazidou I, Grom A, Foell D, Haas JP, Martini A, Gattorno M, Özen S, Prahalad S, Zeft AS, Bohnsack JF, Mellins ED, Ilowite NT, Russo R, Len C, Hilario MO, Oliveira S, Yeung RS, Rosenberg A, Wedderburn LR, Anton J, Schwarz T, Hinks A, Bilginer Y, Park J, Cobb J, Satorius CL, Han B, Baskin E, Signa S, Duerr RH, Achkar JP, Kamboh MI, Kaufman KM, Kottyan LC, Pinto D, Scherer SW, Alarcón-Riquelme ME, Docampo E, Estivill X, Gül A, British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group, Childhood Arthritis Prospective Study (CAPS) Group, Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators, Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group, Biologically Based Outcome Predictors in JIA (BBOP) Group, de Bakker PI, Raychaudhuri S, Langefeld CD, Thompson S, Zeggini E, Thomson W, Kastner DL, Woo P, International Childhood Arthritis Genetics (INCHARGE) Consortium
        

                    Proc Natl Acad Sci U S A.
        
                    2015 Dec 29;
        
                    112(52).
        
                    doi: 10.1073/pnas.1520779112
                            PMID: 26598658
  Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity.

    Ombrello MJ, Kirino Y, de Bakker PI, Gül A, Kastner DL, Remmers EF
        

                    Proc Natl Acad Sci U S A.
        
                    2014 Jun 17;
        
                    111(24).
        
                    doi: 10.1073/pnas.1406575111
                            PMID: 24821759
  Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions.

    Ombrello MJ, Remmers EF, Sun G, Freeman AF, Datta S, Torabi-Parizi P, Subramanian N, Bunney TD, Baxendale RW, Martins MS, Romberg N, Komarow H, Aksentijevich I, Kim HS, Ho J, Cruse G, Jung MY, Gilfillan AM, Metcalfe DD, Nelson C, O'Brien M, Wisch L, Stone K, Douek DC, Gandhi C, Wanderer AA, Lee H, Nelson SF, Shianna KV, Cirulli ET, Goldstein DB, Long EO, Moir S, Meffre E, Holland SM, Kastner DL, Katan M, Hoffman HM, Milner JD
        

                    N Engl J Med.
        
                    2012 Jan 26;
        
                    366(4).
        
                    doi: 10.1056/NEJMoa1102140
                            PMID: 22236196 
          Education
              
            **Saint Louis University, St. Louis, MO**Bachelor of Science, Biology (1997)**Saint Louis University, St. Louis, MO**Medical Degree (2002)             
                        Experience
              
            **Investigator (2017 - Present)**Translational Genetics and Genomics Section, NIAMS, NIH**Assistant Clinical Investigator (2013 - 2017)**Translational Genetics and Genomics Section, NIAMS, NIH**Postdoctoral Fellowship (2011 - 2013)**Inflammatory Disease Section, NHGRI, NIH**Postdoctoral Fellowship (2009 - 2011)**Laboratory of Clinical Investigation, NIAMS, NIH**Clinical Fellowship (2006 - 2009)**Combined Pediatric and Adult RheumatologyCardinal Glennon Children’s Medical Center and Saint Louis University School of Medicine**Residency (2002 - 2006)**Combined Internal Medicine and PediatricsCardinal Glennon Children’s Medical Center and Saint Louis University School of Medicine


Last Updated: October 2023


Back to Top
 About NIAMS
                    Clinical Trials
                    Grants & Funding
                    Health Topics
                    Labs @ NIAMS
              News Room
                    NIAMS Multimedia Library
                    Disclaimer
                    FOIA
                    Contact us
              Privacy Statement
                    Accessibility
                    HHS Vulnerability Disclosure
                    Social Media Moderation Policy
                    NIAMS Archives
        Subscribe to Our E-Newsletters
            Click the button to see different options to sign up for newsletters.
            Click Here to Subscribe
          Follow us on
  
  About NIH
                  Accessibility Support
            FOIA requests
                  No FEAR Act data
            Office of the Inspector General
                  Performance reports
            Privacy Policy