• Ph.D. 1988, Uppsala University, Sweden
• Postdoctoral 1989-92, La Jolla Cancer Research Foundation, La Jolla, CA (now Sanford-Burnham Prebys Medical Discovery Institute)
HONORS & AWARDS
• Benzelius Award in Natural History/Medicine, Royal Society of Sciences, Uppsala, 1993
I worked on eosinophil biology, especially eosinophil adhesion and migration, the role of integrins in these processes, and have collaborated with researchers in the Allergy, Pulmonary and Critical Care Division (of the Department of Medicine) on eosinophil integrins, including their activation states, in various studies of patients with asthma. These states can be assessed with activation-sensitive monoclonal antibodies (mAbs, see Fig 1 for conformations of α4β1 integrin, a receptor for vascular cell adhesion molecule-1, VCAM-1). We have found that activated blood eosinophil β1 integrin, reported by mAb N29, correlates with and predicts lower lung function (Fig 2). We have also studied reporters of platelet and endothelial activation, including P-selectin (platelet activation and P-selectin binding to eosinophils are believed to be upstream of β1 activation), within the Severe Asthma Research Program (SARP). In a new collaboration, also including the Gastroenterology Division, we are currently studying eosinophil β1 activation as a potential non-invasive biomarker for disease activity in eosinophilic esophagitis (EoE), an increasingly common disorder in which the current standard of monitoring is repeat endoscopies with biopsies.
Fig 1. Model of α4β1 integrin conformation with epitopes for activation-sensitive monoclonal antibodies (mAbs). Conformational changes during activation of α4β1 that uncover epitopes for anti-β1 N29, 8E3, HUTS-21, and 9EG7. 1) Inactive, bent conformation; 2) Intermediate-activity, extended, closed conformation; 3) High-activity, extended, open conformation. Conformation 1 is presumably N29-/8E3-/HUTS-21-/9EG7-, conformation 2 N29+/8E3+/HUTS-21-/9EG7-, and conformation 3 N29+/8E3+/HUTS-21+/9EG7+. Green circle, ligand-binding site in the βI domain. Green arrow, cytoplasmic proteins, including talin and kindlins, that bind the β integrin subunit tail and mediate activation. The N29 and 8E3 epitopes are located in the PSI (plexin-semaphorin-integrin) domain, the HUTS-21 epitope in the hybrid domain, and the 9EG7 epitope in the EGF (epidermal growth factor)-like domains. (Figure adapted from Johansson and Mosher 2013)
Fig 2. Eosinophil β1 integrin activation as a potential biomarker in asthma. Receiver operating characteristic (ROC) curve for the ability of blood eosinophil expression of the N29 epitope to predict decreased lung function (as FEV1, forced expiratory volume in 1 s) in a study of inhaled corticosteroid withdrawal in patients with non-severe asthma, compared to the ability of the established biomarkers FENO (fraction of exhaled nitric oxide) or sputum eosinophil percentage. Areas under curve (AUC): N29, 0.93; FENO, 0.86, sputum eosinophils, 0.80. AUC for a perfect biomarker would be 1; for a random, useless one 0.50. (Figure adapted from Johansson et al. 2006)