Citations 2
Targeted deletion of macrophage ferritin heavy chain protects from macrophage ferroptosis in acute respiratory distress syndrome
Zhang, William Z. , Faherty, Lynne , Simmons, Will , Carrasco, Sebastian E. , Hoffman, K., Houghton, Sean , Hsu, Chia-Lang, Haber, Leora, Mancias, Joseph D. , Choi, A.H., Plataki, Maria , Mason, Christopher E. , Cloonan, Suzanne , Zhang, William , Carrasco, Sebastian , Houghton, Sean , Hsu, Chia-Lang , Chung, Kuei-Pin , Ballman, Karla , Redmond, David , Mancias, Joseph D , Schenck, Edward , Mason, Christopher E , Meydan, Cem , Kim, K., Bhatia, Divya , Kallinos, Eleni , Hoffman, Katherine L., Haber, Leora , Meydan, Cem , Mirchandani, Ananda S. , Walmsley, Sarah R. , Goyal, Parag , Ballman, Karla V. , Choi, Augustine M.K.
No container title available | January 8, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Ferritin, consisting of ferritin heavy chain (FTH1) and light chain (FTL) subunits, is an essential intracellular iron storage protein fundamental for cellular function. However, the source and the biological role of extracellular ferritin (ex-ferritin) are less understood. Recent studies have linked elevated serum ex-ferritin with adverse outcomes in individuals with acute respiratory distress syndrome (ARDS). In this study, we demonstrate that both FTH1 and FTL are significantly enriched in the serum, blood monocytes, and alveolar macrophages (AMs) of individuals with ARDS, a phenomenon we successfully replicate in a murine hyperoxia-induced acute lung injury (HALI) model. We show that FTH1 is consistently upregulated in macrophages during lung injury development, and mice with a targeted deletion of FTH1 in myeloid (LysMcre) or resident lung macrophage (Cd11ccre) populations exhibit attenuated HALI. This reduced injury is linked to macrophage resistance to ferroptotic cell death, ferritinophagy, altered airway inflammatory responses, and lower lung extracellular iron and higher levels of FTL-ex-ferritin. Transplantation of FTL-ex-ferritin-enriched bronchoalveolar lavage fluid to wild-type mice protected against HALI. The ratio of FTL-ex-ferritin to FTH1 in the serum of individuals with ARDS who died was higher than that of those that survived, suggesting that the balance between FTH1 and FTL may play a role in injury modulation. Our findings highlight macrophage ferritin as a key regulator of macrophage survival and the response of the lung to injury, presenting a potentially targetable pathway for ARDS treatment.
A Multiomics, Molecular Atlas of Breast Cancer Survivors
Bauer, Brent A. , Schmidt, Caleb M., Ruddy, Kathryn J. , Meydan, Cem , Schmidt, Julian C., Smith, S. , Couch, Fergus J., Earls, John C. , Dudley, Joel T. , Mason, Christopher E. , Zhang, Bodi, Phipps, Stephen M., Schmidt, Michael A. , Dudley, Joel T , Mason, Christopher E , Schmidt, Michael A , Meydan, Cem , Olson, Janet E. , Price, Nathan D.
Metabolites | July 22, 2024 | Volume: 14 | Issue: 7 | Pages: 396
Breast cancer imposes a significant burden globally. While the survival rate is steadily improving, much remains to be elucidated. This observational, single time point, multiomic study utilizing genomics, proteomics, targeted and untargeted metabolomics, and metagenomics in a breast cancer survivor (BCS) and age-matched healthy control cohort (N = 100) provides deep molecular phenotyping of breast cancer survivors. In this study, the BCS cohort had significantly higher polygenic risk scores for breast cancer than the control group. Carnitine and hexanoyl carnitine were significantly different. Several bile acid and fatty acid metabolites were significantly dissimilar, most notably the Omega-3 Index (O3I) (significantly lower in BCS). Proteomic and metagenomic analyses identified group and pathway differences, which warrant further investigation. The database built from this study contributes a wealth of data on breast cancer survivorship where there has been a paucity, affording the ability to identify patterns and novel insights that can drive new hypotheses and inform future research. Expansion of this database in the treatment-naïve, newly diagnosed, controlling for treatment confounders, and through the disease progression, can be leveraged to profile and contextualize breast cancer and breast cancer survivorship, potentially leading to the development of new strategies to combat this disease and improve the quality of life for its victims.