10:40 AM - 11:50 AM Session Chair: Hyungsin Kim, Ph.D.
10:40 AM - 11:15 AM
Chul-Hee Lee, Ph.D. Department of Radiology, Weill Cornell Medicine
Anthracyclines like doxorubicin (DOX) are effective chemotherapeutic agents for cancer patients, including pediatrics, but are limited by cardiotoxic side effects that often go undetected until irreversible cardiac dysfunction occurs. In this study, we present a multimodal molecular imaging strategy for the early detection of DOX-induced cardiotoxicity using a murine model. Male C57BL/6J mice received cumulative DOX doses (24 mg/kg) and were monitored over 16 weeks with echocardiography (echo), PET imaging, and molecular analyses. Echo revealed significant functional decline around 10 weeks, while PET imaging with [$^{68}$Ga]Ga-FAPI-04— targeting fibroblast activation protein-alpha (FAP)—identified increased cardiac signal as early as 2 weeks post-treatment, before functional or histological changes were evident. This early FAPI uptake strongly correlated with FAP expression and markers of fibrotic remodeling. Concurrently, dynamic [3-$^{11}$C]pyruvate PET revealed impaired myocardial oxidative metabolism by 4 weeks, characterized by increased tracer flux and diminished labeling of TCA cycle intermediates. These metabolic changes were linked to downregulation of mitochondrial pyruvate carriers (MPC1/2), confirmed by transcriptomic and protein analyses, and corroborated in DOX-treated human cardiomyocytes. Together, these findings demonstrate that fibrotic activation and metabolic dysfunction precede overt cardiac impairment in DOX cardiotoxicity. Imaging these molecular events with FAPI and pyruvate PET provides a non-invasive, translatable approach to detect subclinical cardiac injury and guide early interventions in patients receiving anthracycline chemotherapy.
11:15 AM - 11:50 AM
Taehee Han, Ph.D. Columbia University
Living organisms, from microbes to mammals, rely on complex metabolic networks to sustain life. Systems Metabolic Engineering (SME) -a multidisciplinary strategy integrating metabolic engineering, systems biology, and synthetic biology - has revolutionized our ability to rationally redesign these networks.
In microbial systems, we developed a new broad-host-range synthetic sRNA platform, integrated multi-omics analyses, and employed various metabolic engineering strategies to construct efficient microbial cell factories for bio-based production of polymer monomers. These efforts enabled the construction of new synthetic metabolic pathways, identification of novel transporters, elimination of toxic by-products, and optimization of fermentation processes, achieving the world’s best production performance suitable for industrial commercialization. Importantly, this work demonstrated the feasibility of building a competitive bioindustry capable of addressing the challenges of traditional petrochemical industries and environmental sustainability.
Expanding this strategy beyond microbial platforms, we applied SME to reprogram mammalian metabolism, focusing on resurrecting essential amino acid (EAA) biosynthetic capabilities that were lost during metazoan evolution. By designing and introducing synthetic pathways composed foreign genes, we successfully restored de novo EAA biosynthesis in mammalian cells. Multi-omics validation confirmed functional metabolic rewiring, enabling sustained cell proliferation even under amino acid-deprived conditions. This study demonstrates the feasibility of reprogramming mammalian cells with synthetic pathways, suggesting a new paradigm to engineer immune cells capable of maintaining functionality under nutrient-depleted tumor microenvironment. Ultimately, he expansion of SME from microbial factories to mammalian cell therapies lays a foundation for next-generation cancer immunotherapies, bacterial drug delivery, and future life-support systems for long-duration spaceflight.
