Summary

Michael Ombrello, M.D., joined the Pediatric Translational Research Branch as a Tenure-Track Investigator in 2017.  Dr. Ombrello graduated from the Illinois Mathematics and Science Academy in 1993.  He matriculated to Saint Louis University as a Pre-Medical scholar, where he earned both a B.S. in Biology and an M.D.  He obtained residency training in combined Internal Medicine and Pediatrics at the Cardinal Glennon Children’s Medical Center and Saint Louis University Hospital, where he also received subspecialty training in combined adult and pediatric rheumatology.  During his rheumatology fellowship, Dr. Ombrello’s desire to explore the underpinnings of inflammatory diseases blossomed, leading him to pursue postdoctoral training in the genetics and genomics of inflammation with Daniel Kastner at the NIH.  As the inaugural NIAMS Henry Metzger Scholar in Translational Medicine, he performed genomic studies of Behçet’s disease and established an international collaboration to study the genetics of systemic juvenile idiopathic arthritis (sJIA).  He also identified novel deletions of PLCG2 in 3 families with a novel autoinflammatory disease, PLCG2-associated antibody deficiency and immune dysregulation (PLAID).  In 2013 he was appointed by NIAMS as an Assistant Clinical Investigator and established the Translational Genetics and Genomics Unit.

Dr. Ombrello is board certified in both rheumatology and pediatric rheumatology.  He leads the genetic investigations of sJIA for the International Childhood Arthritis Genetics (INCHARGE) Consortium.  He is actively involved in a range of organizations, including the American College of Rheumatology and the Childhood Arthritis Rheumatology Research Alliance.  He has received numerous local and national awards and honors, including NIAMS and NIAID Merit Awards, the American College of Rheumatology’s Distinguished Fellow Award, the NIH Fellows’ Award for Research Excellence and the NIH Director’s Award.

Research Statement

The Translational Genetics and Genomics Unit is a research group focused on understanding the mechanisms that underlie inflammatory and autoimmune disease.  We have a particular interest in genetically-complex diseases, such as Still’s disease/systemic juvenile arthritis and Behçet’s disease, whose pathophysiologies manifest dysfunction of both innate and adaptive immune mechanisms.  Working with large international collaborations, we are engaged in integrated genomic investigations of well-phenotyped patient collections.  We are also seeking to better understand the mechanisms of seemingly unprovoked inflammation through the study of individuals and families with monogenic inflammatory diseases, such as PLCG2 associated antibody deficiency and immune dysregulation (PLAID), together with phenotypically-similar but genetically-complex disorders, such as common variable immune deficiency.  Through the biologic knowledge that our studies produce, we hope to identify novel therapeutic targets to ultimately improve the lives of individuals affected by chronic inflammatory and rheumatic diseases.

Scientific Publications

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

Assistant Clinical Investigator (2013 - 2017)
Translational Genetics and Genomics Unit, 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 Rheumatology
Cardinal Glennon Children’s Medical Center and Saint Louis University School of Medicine

Residency (2002 - 2006)
Combined Internal Medicine and Pediatrics
Cardinal Glennon Children’s Medical Center and Saint Louis University School of Medicine

Last Updated: July 2022