Research Topics
The Human Eosinophil Section conducts basic and translational research related to the role of the eosinophil and eosinophil activation in disease pathogenesis, with the ultimate goal of developing novel diagnostic tools and treatment approaches for hypereosinophilic syndromes and other conditions associated with marked eosinophilia, including helminth infection.
Using a translational approach, distinct clinical subgroups of patients with HES have been identified and characterized, including a myeloproliferative form of HES that includes FIP1L1/PDGFRA-positive chronic eosinophilic leukemia and an autosomal dominant form of familial eosinophilia that has been mapped to chromosome 5q31-33. Laboratory studies have focused on the role of eosinophils and eosinophil activation in producing the very different clinical presentations and outcomes of these disorders. Clinical trials using targeted therapies, including imatinib mesylate and monoclonal antibodies to IL-5 and IL-5 receptor, have provided additional insight into the etiology and pathogenesis of HES variants.
Eosinophilia is common in human helminth infection and may be associated with pathologic sequelae that mimic the clinical findings in HES, including tissue fibrosis and "allergic" manifestations. Furthermore, these manifestations may be produced or exacerbated by anthelminthic therapy. Prior research in the Helminth Immunology Section has demonstrated that these exacerbations are accompanied by an increase in IL-5, eosinophils, and markers of eosinophil activation. Consequently, a second major focus of our section is to explore further the role of the eosinophil in post-treatment reactions and to use novel approaches to limit the pathology seen in these settings.
Clinicians in the Human Eosinophil Section, along with others in the Laboratory of Parasitic Diseases, form the Clinical Parasitology Section, which has played a major role in the training of physicians for careers in tropical medicine.
Biography
Dr. Klion earned her B.A. from Princeton University and her M.D. from New York University School of Medicine. After completing a residency in internal medicine at Johns Hopkins University, she was a postdoctoral fellow in the Laboratory of Parasitic Diseases from 1989 to 1991. She completed her fellowship in infectious diseases at the University of Iowa Hospitals and Clinics in Iowa City, Iowa, where she was appointed an assistant professor in the division of infectious diseases prior to returning to the Laboratory of Parasitic Diseases in 1997 as a staff clinician. She became a tenure-track clinical investigator in the Laboratory of Parasitic Diseases in 2009 and a senior clinical investigator in 2014.
Selected Publications
- Kuang FL, Legrand F, Makiya M, Ware J, Wetzler L, Brown T, Magee T, Piligian B, Yoon P, Ellis JH, Sun X, Panch SR, Powers A, Alao H, Kumar S, Quezado M, Yan L, Lee N, Kolbeck R, Newbold P, Goldman M, Fay MP, Khoury P, Maric I, Klion AD. Benralizumab for PDGFRA-Negative Hypereosinophilic Syndrome. N Engl J Med. 2019;380(14):1336-1346.
- Panch SR, Bozik ME, Brown T, Makiya M, Prussin C, Archibald DG, Hebrank GT, Sullivan M, Sun X, Wetzler L, Ware J, Fay MP, Dunbar CE, Dworetzky SI, Khoury P, Maric I, Klion AD. Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes. Blood. 2018;132(5):501-509.
- Legrand F, Herrick J, Makiya M, Ramanathan R, Thompson R, Rampertaap S, Stoddard J, Ware J, Fay MP, Holland-Thomas N, Nutman TB, Klion AD. A Randomized, Placebo-controlled, Double-blind Pilot Study of Single-dose Humanized Anti-IL5 Antibody (Reslizumab) for the Reduction of Eosinophilia Following Diethylcarbamazine Treatment of Loa loa Infection. Clin Infect Dis. 2021;73(7):e1624-e1631.
- Hong SG, Sato N, Legrand F, Gadkari M, Makiya M, Stokes K, Howe KN, Yu SJ, Linde NS, Clevenger RR, Hunt T, Hu Z, Choyke PL, Dunbar CE, Klion AD, Franco LM. Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration. Blood. 2020;136(23):2667-2678.
- Bohrer AC, Castro E, Tocheny CE, Assmann M, Schwarz B, Bohrnsen E, Makiya MA, Legrand F, Hilligan KL, Baker PJ, Torres-Juarez F, Hu Z, Ma H, Wang L, Niu L, Wen Z, Lee SH, Kamenyeva O, Tuberculosis Imaging Program., Kauffman KD, Donato M, Sher A, Barber DL, Via LE, Scriba TJ, Khatri P, Song Y, Wong KW, Bosio CM, Klion AD, Mayer-Barber KD. Rapid GPR183-mediated recruitment of eosinophils to the lung after Mycobacterium tuberculosis infection. Cell Rep. 2022;40(4):111144.
Related Scientific Focus Areas
Microbiology and Infectious Diseases
View additional Principal Investigators in Microbiology and Infectious Diseases
This page was last updated on Wednesday, August 24, 2022