CBE - Investigating the Role of Cardiac-Resident Macrophages in Obese Heart
This project aims to engineer a physiologically relevant in vitro 3D human obese heart model incorporating hypertrophic adipocytes, human iPSC-derived atrial cardiomyocytes and macrophages to investigate metabolic, electrophysiological, and immunomodulatory mechanisms underlying obesity-induced cardiac dysfunction. Human adipose-derived stem cells will be bioprinted in hydrogels, differentiated into adipocytes, and stimulated with fatty acids to mimic high-fat diet conditions. These constructs will be cocultured with a-iCMs to assess myocardial glucose uptake, insulin receptor activation, cytokine profiles, contractile function, and gap junction integrity. Naïve macrophages will be introduced to evaluate their recruitment, polarization, phagocytic activity, and effects on cardiomyocyte function and remodeling. Students will participate in bioprinting, cell culture, molecular assays, live-cell imaging, and data analysis.
The Zorlutuna Lab at the University of Notre Dame is a dynamic, interdisciplinary environment combining 3D bioprinting, organ-on-chip systems, and stem cell biology to model complex human diseases. This project is critical because current in vitro cardiac models lack epicardial adipose tissue and immune components, limiting our understanding of obesity-related heart disease. By engineering a 3D human obese heart with hypertrophic adipocytes, hiPSC-derived cardiomyocytes, and macrophages, we aim to replicate key metabolic, inflammatory, and electrophysiological changes and uncover macrophage-driven repair mechanisms. Alongside this work, the lab pursues innovative studies on cardiac fibrosis, chemotherapeutic-induced cardiotoxicity, breast cancer mechanisms and tumor–stroma interactions, offering students a highly collaborative, technology-rich setting with strong translational impact.