Rheumatology
Schulert Lab

Schulert Research Lab

The primary focus of the Schulert lab is the pathogenesis of severe inflammatory disorders of childhood, in particular systemic juvenile idiopathic arthritis (systemic JIA). Although systemic JIA is considered a subtype of JIA, it has distinct clinical and epidemiologic characteristics, notably prominent extra-articular features, including prolonged spiking fevers, rash, lymphadenopathy and serositis.  The pathogenesis of systemic JIA is incompletely understood, but recent work suggests that it fits the paradigm of autoinflammatory disorders.  In contrast to classic autoimmune disorders, which are associated by autoreactive, antigen-specific T cells and autoantibodies, autoinflammatory disorders display abnormal activation of innate immune effector cells, most notably monocytes/macrophages and neutrophils.

Children with systemic JIA are at high risk for life threatening complications, including macrophage activation syndrome (MAS) and chronic lung disease. MAS is a potentially life-threatening episode of overwhelming inflammation occurring in 10-30% of systemic JIA patients, and is characterized by fevers, cytopenias, coagulopathy, liver and central nervous system dysfunction, and a systemic cytokine storm. Chronic lung disease (SJIA-LD) is a recently recognized and poorly understood complication that has emerged as a key driver of systemic JIA morbidity and mortality. The long-term goal of the lab is to determine the course and pathophysiology of severe complications of systemic JIA, leading to targeted therapy that improves patient outcomes.

Publications

Kuhn, KA; Stahly, A; Konig, MF; Carandang, K; Herndon, C; Backman, C; Callahan, LF; Schulert, G; Fraenkel, L; Ogdie, A; et al. Impact of the COVID-19 Pandemic on Early Career Investigators in Rheumatology: Recommendations to Address Challenges to Early Research Careers. Arthritis Care and Research. 2022.

Bahakel, H; Murphy, CR; Frenck, RW; Grimley, M; Phillips, C; Schulert, G; Spearman, P; Courter, JD; Paulsen, GC; Danziger-Isakov, LA. 1119. Covid-19 Mab Use in High-Risk Pediatric Patients. Open Forum Infectious Diseases. 2022; 9.

Vega-Fernandez, P; Ting, TV; Mar, DA; Schapiro, AH; Deluna, MD; Saper, VE; Grom, AA; Schulert, GS; Fairchild, RM. Lung Ultrasound in Children With Systemic Juvenile Idiopathic Arthritis-Associated Interstitial Lung Disease. Arthritis Care and Research. 2022.

Bahakel, H; Murphy, C; Frenck, RW; Grimley, MS; Marsh, RA; Paulsen, GC; Haslam, DB; Phillips, CL; Courter, J; Spearman, P; et al. Single Site Experience of the use of Monoclonal Antibodies for the Treatment of COVID-19 in High-risk Pediatric and Young Adult Patients. Pediatric Infectious Disease Journal. 2022; 41:985-988.

Son, MB F; Berbert, L; Young, C; Dallas, J; Newhams, M; Chen, S; Ardoin, SP; Basiaga, ML; Canny, SP; Crandall, H; et al. Postdischarge Glucocorticoid Use and Clinical Outcomes of Multisystem Inflammatory Syndrome in Children. JAMA Network Open. 2022; 5.

Schulert, GS. The Big Bad Wolf: Macrophage Activation Syndrome in Childhood-Onset Systemic Lupus Erythematosus. Journal of Rheumatology. 2022; 49:1082-1084.

Rao, S; Jing, N; Liu, X; Lorman, V; Maltenfort, M; Schuchard, J; Wu, Q; Tong, J; Razzaghi, H; Mejias, A; et al. Clinical Subphenotypes of Multisystem Inflammatory Syndrome in Children: An EHR-based cohort study from the RECOVER program. 2022.

Chen, G; Deutsch, GH; Schulert, GS; Zheng, H; Jang, SR; Trapnell, B; Lee, PY; Macaubas, C; Ho, K; Schneider, C; et al. Identification of Distinct Inflammatory Programs and Biomarkers in Systemic Juvenile Idiopathic Arthritis and Related Lung Disease by Serum Proteome Analysis. Arthritis and Rheumatology. 2022; 74:1271-1283.

Henderson, LA; Canna, SW; Friedman, KG; Gorelik, M; Lapidus, SK; Bassiri, H; Behrens, EM; Kernan, KF; Schulert, GS; Seo, P; et al. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 3. Arthritis and Rheumatology. 2022; 74:e1-e20.

Verweyen, EL; Schulert, GS. Interfering with interferons: targeting the JAK-STAT pathway in complications of systemic juvenile idiopathic arthritis (SJIA). Rheumatology. 2022; 61:926-935.

Schulert, GS; Blum, SA; Cron, RQ. Host genetics of pediatric SARS-CoV-2 COVID-19 and multisystem inflammatory syndrome in children. Current Opinion in Pediatrics. 2021; 33:549-555.

Angeles-Han, ST; Miraldi Utz, V; Thornton, S; Schulert, G; Rodriguez-Smith, J; Kauffman, A; Sproles, A; Mwase, N; Hennard, T; Grom, A; et al. S100 proteins, cytokines, and chemokines as tear biomarkers in children with juvenile idiopathic arthritis-associated uveitis. Ocular Immunology and Inflammation. 2021; 29:1616-1620.

Erkens, R; Esteban, Y; Towe, C; Schulert, G; Vastert, S. Pathogenesis and Treatment of Refractory Disease Courses in Systemic Juvenile Idiopathic Arthritis: Refractory Arthritis, Recurrent Macrophage Activation Syndrome and Chronic Lung Disease. Rheumatic Disease Clinics of North America. 2021; 47:585-606.

Gao, DK; Salomonis, N; Henderlight, M; Woods, C; Thakkar, K; Grom, AA; Thornton, S; Jordan, MB; Wikenheiser-Brokamp, KA; Schulert, GS. IFN-γ is essential for alveolar macrophage-driven pulmonary inflammation in macrophage activation syndrome. JCI insight. 2021; 6.

Walsh, KB; Zimmerman, KD; Zhang, X; Demel, SL; Luo, Y; Langefeld, CD; Wohleb, E; Schulert, G; Woo, D; Adeoye, O. miR-181a Mediates Inflammatory Gene Expression After Intracerebral Hemorrhage: An Integrated Analysis of miRNA-seq and mRNA-seq in a Swine ICH Model. Journal of Molecular Neuroscience. 2021; 71:1802-1814.

Rodriguez-Smith, JJ; Verweyen, EL; Clay, GM; Esteban, YM; de Loizaga, SR; Baker, EJ; Do, T; Dhakal, S; Lang, SM; Grom, AA; et al. Inflammatory biomarkers in COVID-19-associated multisystem inflammatory syndrome in children, Kawasaki disease, and macrophage activation syndrome: a cohort study. The Lancet. Rheumatology. 2021; 3:e574-e584.

Verweyen, EL; Pickering, A; Grom, AA; Schulert, GS. Distinct Gene Expression Signatures Characterize Strong Clinical Responders Versus Nonresponders to Canakinumab in Children With Systemic Juvenile Idiopathic Arthritis. Arthritis and Rheumatology. 2021; 73:1334-1340.

Schulert, GS. The IL-18/IFNγ axis in systemic JIA and MAS-new answers, more questions. Rheumatology. 2021; 60:3045-3047.

Ombrello, MJ; Schulert, GS. COVID-19 and cytokine storm syndrome: are there lessons from macrophage activation syndrome?. Translational Research. 2021; 232:1-12.

Danziger-Isakov, L; Khalil, N; Divanovic, A; Frenck, R; Grimley, M; Iliopoulos, I; Marsh, R; Paulsen, G; Phillips, CL; Schulert, G; et al. Novel Treatment of Infant With COVID-19 With the Sialidase Fusion Protein, DAS181. Pediatric Infectious Disease Journal. 2021; 40:e234-e235.

Cheung, P; Schaffert, S; Chang, SE; Dvorak, M; Donato, M; Macaubas, C; Foecke, MH; Li, TM; Zhang, L; Coan, JP; et al. Repression of CTSG, ELANE and PRTN3-mediated histone H3 proteolytic cleavage promotes monocyte-to-macrophage differentiation. Nature Immunology. 2021; 22:711-722.

Henderson, LA; Canna, SW; Friedman, KG; Gorelik, M; Lapidus, SK; Bassiri, H; Behrens, EM; Ferris, A; Kernan, KF; Schulert, GS; et al. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 2. Arthritis and Rheumatology. 2021; 73:e13-e29.

Murphy, ME; Clay, G; Danziger-Isakov, L; Schulert, G; Paulsen, GC. Acute severe respiratory syndrome coronavirus-2 treatment overview for pediatrics. Current Opinion in Pediatrics. 2021; 33:129-135.

King, CD; Boggero, IA; Schulert, GS; Pickerill, HM; Cole, S. Preliminary evidence for conserved transcriptional response to adversity in adults with temporomandibular disorder. PAIN Reports. 2021; 6.

Aljaberi, N; Tronconi, E; Schulert, G; Grom, AA; Lovell, DJ; Huggins, JL; Henrickson, M; Brunner, HI. The use of S100 proteins testing in juvenile idiopathic arthritis and autoinflammatory diseases in a pediatric clinical setting: a retrospective analysis. Pediatric Rheumatology. 2020; 18.

Cron, RQ; Schulert, GS; Tattersall, RS. Defining the scourge of COVID-19 hyperinflammatory syndrome. The Lancet. Rheumatology. 2020; 2:e727-e729.

Lin, B; Berard, R; Al Rasheed, A; Aladba, B; Kranzusch, PJ; Henderlight, M; Grom, A; Kahle, D; Torreggiani, S; Aue, AG; et al. A novel STING1 variant causes a recessive form of STING-associated vasculopathy with onset in infancy (SAVI). Journal of Allergy and Clinical Immunology. 2020; 146:1204-1208.e6.

Henderson, LA; Canna, SW; Friedman, KG; Gorelik, M; Lapidus, SK; Bassiri, H; Behrens, EM; Ferris, A; Kernan, KF; Schulert, GS; et al. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 1. Arthritis and Rheumatology. 2020; 72:1791-1805.

Schulert, GS. The Storm Beneath the Storm: MAS-HLH in Inflammatory Myopathies. Journal of Rheumatology. 2020; 47:1461-1463.

Schulert, GS. Can tocilizumab calm the cytokine storm of COVID-19?. The Lancet. Rheumatology. 2020; 2:e449-e451.

Canna, SW; Schulert, GS; de Jesus, A; Pickering, A; Brunner, H; Gadina, M; Levine, S; Goldbach-Mansky, R; Boutelle, J; Sinha, R; et al. Proceedings from the 2nd Next Gen Therapies for Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome symposium held on October 3-4, 2019. Pediatric Rheumatology. 2020; 18.

Henderson, LA; Canna, SW; Schulert, GS; Volpi, S; Lee, PY; Kernan, KF; Caricchio, R; Mahmud, S; Hazen, MM; Halyabar, O; et al. On the Alert for Cytokine Storm: Immunopathology in COVID-19. Arthritis and Rheumatology. 2020; 72:1059-1063.

Schulert, GS; Cron, RQ. The genetics of macrophage activation syndrome. Genes and Immunity. 2020; 21:169-181.

de Jesus, AA; Hou, Y; Brooks, S; Malle, L; Biancotto, A; Huang, Y; Calvo, KR; Marrero, B; Moir, S; Oler, AJ; et al. Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases. Journal of Clinical Investigation. 2020; 130:1669-1682.

Verweyen, E; Holzinger, D; Weinhage, T; Hinze, C; Wittkowski, H; Pickkers, P; Albeituni, S; Verbist, K; Nichols, KE; Schulert, G; et al. Synergistic Signaling of TLR and IFNα/β Facilitates Escape of IL-18 Expression from Endotoxin Tolerance. American Journal of Respiratory and Critical Care Medicine. 2020; 201:526-539.

Ferrara, G; Giani, T; Lieberman, SM; Kremer, C; Hong, S; Indolfi, G; Schulert, G; Cron, RQ; Mannion, ML; Lapidus, S; et al. Alagille Syndrome and Chronic Arthritis: An International Case Series. Journal of Pediatrics. 2020; 218:228-230.e1.

Yasin, S; Fall, N; Brown, RA; Henderlight, M; Canna, SW; Girard-Guyonvarc'h, C; Gabay, C; Grom, AA; Schulert, GS. IL-18 as a biomarker linking systemic juvenile idiopathic arthritis and macrophage activation syndrome. Rheumatology. 2020; 59:361-366.

Yasin, S; Solomon, K; Canna, SW; Girard-Guyonvarc'h, C; Gabay, C; Schiffrin, E; Sleight, A; Grom, AA; Schulert, GS. IL-18 as therapeutic target in a patient with resistant systemic juvenile idiopathic arthritis and recurrent macrophage activation syndrome. Rheumatology. 2020; 59:442-445.

Lee, PY; Schulert, GS; Canna, SW; Huang, Y; Sundel, J; Li, Y; Hoyt, KJ; Blaustein, RB; Wactor, A; Do, T; et al. Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Annals of the Rheumatic Diseases. 2020; 79:225-231.

Abid, Q; Best Rocha, A; Larsen, CP; Schulert, G; Marsh, R; Yasin, S; Patty-Resk, C; Valentini, RP; Adams, M; Baracco, R. APOL1-Associated Collapsing Focal Segmental Glomerulosclerosis in a Patient With Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset in Infancy (SAVI). American Journal of Kidney Diseases. 2020; 75:287-290.

Shenoi, S; Nanda, K; Schulert, GS; Bohnsack, JF; Cooper, AM; Edghill, B; Gillispie-Taylor, MC; Goldberg, B; Halyabar, O; Mason, TG; et al. Physician practices for withdrawal of medications in inactive systemic juvenile arthritis, Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey. Pediatric Rheumatology. 2019; 17.

Saper, VE; Chen, G; Deutsch, GH; Guillerman, RP; Birgmeier, J; Jagadeesh, K; Canna, S; Schulert, G; Deterding, R; Xu, J; et al. Emergent high fatality lung disease in systemic juvenile arthritis. Annals of the Rheumatic Diseases. 2019; 78:1722-1731.

Schulert, GS; Yasin, S; Carey, B; Chalk, C; Do, T; Schapiro, AH; Husami, A; Watts, A; Brunner, HI; Huggins, J; et al. Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease: Characterization and Risk Factors. Arthritis and Rheumatology. 2019; 71:1943-1954.

Niu, X; Schulert, GS. Functional Regulation of Macrophage Phenotypes by MicroRNAs in Inflammatory Arthritis. Frontiers in Immunology. 2019; 10.

Schulert, GS; Zhang, K. Genetics of Acquired Cytokine Storm Syndromes. Cytokine Storm Syndrome. 2019.

Brunner, HI; Holland, MJ; Beresford, MW; Ardoin, SP; Appenzeller, S; Silva, CA; Flores, F; Aydin, PO A; Wenderfer, SE; Levy, DM; et al. American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus. Arthritis Care and Research. 2019; 71:579-590.

Thornton, S; Tan, R; Sproles, A; Do, T; Schick, J; Grom, AA; DeLay, M; Schulert, GS. A Multiparameter Flow Cytometry Analysis Panel to Assess CD163 mRNA and Protein in Monocyte and Macrophage Populations in Hyperinflammatory Diseases. Journal of Immunology. 2019; 202:1635-1643.

Schulert, GS. Immunology of Auto-inflammatory Syndromes. Auto-Inflammatory Syndromes. 2019.

DeSena, AD; Do, T; Schulert, GS. Systemic autoinflammation with intractable epilepsy managed with interleukin-1 blockade. Journal of Neuroinflammation. 2018; 15.

Ter Haar, NM; van Delft, AL J; Annink, KV; van Stel, H; Al-Mayouf, SM; Amaryan, G; Anton, J; Barron, KS; Benseler, S; Brogan, PA; et al. In silico validation of the Autoinflammatory Disease Damage Index. Annals of the Rheumatic Diseases. 2018; 77:1599-1605.

Yasin, S; Schulert, GS. Systemic juvenile idiopathic arthritis and macrophage activation syndrome: update on pathogenesis and treatment. Current Opinion in Rheumatology. 2018; 30:514-520.

Harry, O; Schulert, GS; Frenck, RW; Shapiro, AH; Woltmann, JL; Smith, JA; Grom, AA. Cat-Scratch Disease, a Diagnostic Consideration for Chronic Recurrent Multifocal Osteomyelitis. Journal of Clinical Rheumatology. 2018; 24:287-290.

Schulert, GS; Zhang, M; Husami, A; Fall, N; Brunner, H; Zhang, K; Cron, RQ; Grom, AA. Brief Report: Novel UNC13D Intronic Variant Disrupting an NF-κB Enhancer in a Patient With Recurrent Macrophage Activation Syndrome and Systemic Juvenile Idiopathic Arthritis. Arthritis and Rheumatology. 2018; 70:963-970.

Cron, RQ; Schulert, GS; Zhang, M; Husami, A; Fall, N; Brunner, H; Zhang, K; Grom, AA. Novel UNC13D intronic variant disrupting a NF κB enhancer in a patient with recurrent macrophage activation syndrome and systemic juvenile idiopathic arthritis. Journal of Immunology. 2018; 200:45.21-45.21.

Schulert, GS; Canna, SW. Convergent pathways of the hyperferritinemic syndromes. International Immunology. 2018; 30:195-203.

Contact Us

A photo of Grant Schulert, MD, PhD.

Grant Schulert, MD, PhD
Assistant Professor, Division of Rheumatology

phone: 513-363-4676
email: grant.schulert@cchmc.org