DFG Funding for Marija Gredić: Investigating the Role of Cathepsin D in COPD-associated pulmonary hypertension

Dr. Marija Gredić, a DZL scientist at Justus Liebig University Giessen (DZL site UGMLC), has been awarded a research grant of € 324 032 for three years (2026–2028) from German Research Foundation (DFG) to study novel mechanisms driving pulmonary hypertension in COPD.

Dr. Gredić’s group recently showed that interactions between interstitial macrophages and pulmonary vascular cells promote vascular remodeling in COPD, driven by smoke-specific rather than hypoxia-dependent signaling. An important player in this process appears to be Cathepsin D (Cts-D), a lysosomal enzyme highly expressed in macrophages. The team found strong upregulation of Cts-D in the remodeled pulmonary vasculature of smoke-exposed mice and COPD patients, and demonstrated in vitro the ability of this protein to enhance proliferation of pulmonary vascular cells.

With this new funding, Dr. Gredić aims to uncover the cellular mechanisms by which Cts-D promotes cellular proliferation and to determine its functional relevance for pulmonary vascular remodeling in vivo using cell type-specific knockout models and neutralizing antibodies. Furthermore, findings from the mouse studies will be validated in human tissue samples, and circulating Cts-D will be evaluated as a potential biomarker for COPD-associated pulmonary hypertension.

Ultimately, this research seeks to identify novel therapeutic targets to halt or even reverse pulmonary vascular remodeling and disease progression in COPD patients.

October, 2025