Alexei A. Grom, MD

Professor, UC Department of Pediatrics

Phone 513-636-3339

Fax 513-636-3328

Email alexei.grom@cchmc.org

The research of Alexei Grom, MD, has mainly involved two translational projects focused on two autoimmune diseases – systemic juvenile rheumatoid arthritis and juvenile dermatomyositis. In both projects, recent advances of cellular immunology are applied to these diseases to promote better understanding of their pathogenesis and treatment.

Systemic onset juvenile rheumatoid arthritis and an associated condition known as macrophage activation syndrome are severe and often devastating illnesses. The pathological mechanisms are not known but Dr. Alexei Grom has focused his research on NK and cytotoxic cell function in this disease. The rationale for this approach has been based on the strong clinical similarities between MAS and the better understood autosomal recessive disorder familial hemophagocytic lymphohistiocytosis, in which the uncontrolled proliferation of T cells and macrophages has been recently associated with decreased NK cell and cytotoxic cell functions secondary to mutations in the gene encoding perforin. Recent observations suggest as in FHLH, MAS patients also have profoundly depressed NK function. Moreover, a large subgroup of systemic JRA patients has very similar immunologic abnormalities. Combined with the evidence of the immunoregulatory role of NK cells in many immune responses, this suggests that NK dysfunction is relevant to the pathogenesis of MAS. New directions have thus been established for research in this poorly understood disease.

Juvenile dermatomyositis is a chronic inflammatory condition involving primarily muscles and skin. The most characteristic feature of JDM is vascular damage associated with the capillary necrosis that eventually leads to capillary loss and tissue ischemia. The project is based on the hypothesis that capillary loss in this condition may be caused by angiostatic chemokines that are prominent in the inflammatory response in the affected muscles.

MD: Leningrad (St. Petersburg) Pediatric Medical Institute, Russia, 1986. 

Residency: Leningrad (St. Petersburg) Medical Institute, Russia, 1988; Children's Hospital Medical Center, Cincinnati, Ohio, 1998. 

Fellowship: Leningrad (St. Petersburg) Pediatric Medical Institute, Russia, 1991; Children's Hospital Medical Center, Cincinnati, Ohio, 1995. 

Certification: Pediatrics, 1999.

De Benedetti F, Brunner HI, Ruperto N, Kenwright, A, Ravelli A, Schneider, Woo P, Wouters C, Zemel, L, Burgos-Vargos R, Dolezalova P, Grom AA, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A. Tocilizumab in systemic juvenile idiopathic arthritis: a randomized trial. New Engl J Med. 367:2385-95. 2012.

Sikora KA, Fall N, Thornton S and Grom AA. A Markedly Low-Level of Interferon-Induced Gene Expression Distinguishes Active Systemic Juvenile Idiopathic Arthritis Synovium From other JIA subtypes: Implications for Pathogenesis of Macrophage Activation Syndrome. Arthritis Rheum. 64:3799-808. 2012.

Ruperto N, Brunner HI, Quartier P, Constantin T, Wulfraat N, Horneff G, Brik R, McCann L, Nistala K, Wouters C, Cimaz R, Ferrandiz MA, Flato B, Grom AA, Magnusson, Ozen S, Abrams K, Kim D, Martini A, Lovell DJ. Canakinumab in systemic juvenile arthritis with active systemic features. New Engl J Med. 367:2396-406. 2012.

Mellins ED, Macubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nature Reviews Rheumatology. 7:416-26. 2011.

Sumegi J, Barnes MG, Lee S, Villanueva J, Zhang K, Nestheide SV, Risma K, Grom AA, AH Filipovich. Gene Expression Profiling of peripheral blood mononuclear cells from patients with untreated familial hemophagocytic lymphohistiocytosisBlood. 117:151-60. 2011.

Barnes MG, Grom AA, Thompson SD, Griffin TA, Luyrink LK, Colbert, RA, David N, Glass DN. Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis. Arthritis Rheum. 2010.

Hinze CH, Fall N, Thornton S, Griffin TA, Thompson SD, Colbert RA, Glass DN, Michael G, Barnes BG, Grom AA. Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis. Arthritis Res Ther. 2010.

Barnes MG, Grom AA, Thompson SD, Ilowite NT, Olson JC, Sherry DD, Gottlieb BS, Aronow BJ, Pavlidis P, Hinze C, Thornton S, Griffin TA, Colbert CA, DN Glass. Gene Expression Signatures in new onset untreated juvenile idiopathic arthritis. Arthritis Rheum. 60:2102-12. 2009.

Zhang K, Biroscak J, Glass DN, Thompson S, Finkel T, Murray P, Binstadt B, Filipovich A, Grom AA. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13D polymorphisms. Arthritis Rheum. x58:2892-6. 2008.

Fall N, Barnes M, Thornton S, Luyrink L, Olson J, Ilowite NT, Gottlieb E, Griffin T, Sherry DD, Thompson S, Glass DN, Colbert RA, Grom AA. Gene expression profiling in peripheral blood from patients with  untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome. Arthritis Rheum. 56:3793-804. 2007.