Natalie Porat-Shliom, Ph.D.

Liver cancer remains among the most lethal malignancies, in part because tumors are mosaics of distinct cell states that fuel drug resistance and relapse. A useful roadmap for understanding this heterogeneity already exists in the healthy liver. Along the portal-central axis of each lobule, hepatocytes adopt graded transcriptional and metabolic programs, a physiological phenomenon known as liver zonation (Cunningham and Porat-Shliom, Frontiers in Physiology, 2021). Zonation is thought to address a core organizational challenge: the liver must run incompatible biochemical pathways in parallel, and it does so by distributing them across space, like a continuous “assembly line”. Yet the absence of physical boundaries between the zones makes them difficult to study (Porat-Shliom, Current Opinion in Cell Biology, 2024). Bulk assays average signals across zones, obscuring the very diversity that likely shapes physiology and the underlying vulnerability to injury and malignant transformation.

Our goal is to define the mechanisms that maintain physiological heterogeneity in the healthy liver and determine how their disruption in Metabolically Associated Steatotic Liver Disease (MASLD), a major precursor to Hepatocellular Carcinoma (HCC), drives pathological remodeling. To achieve this, the Porat-Shliom laboratory integrates light and electron microscopy tools, an AI-guided analysis pipeline for segmentation, spatial registration, and single-cell tracking, with zone-resolved isolation for protein and metabolite profiling. In collaboration with NIH clinicians, complementary studies are conducted on human liver tissue. This integrative platform allows us to quantify how organelle organization and inter-organelle connectivity encode metabolic flexibility, and to identify when, where, and how these programs fail during MASLD and early hepatocarcinogenesis.

Dr. Porat-Shliom received her B.Sc. in Biology, M.Sc. in Neurobiology, and Ph.D. in Cell Biology from Tel Aviv University. Her doctoral research focused on investigating endocytosis and Ras signaling using live‑cell imaging. She then completed her postdoctoral training with Dr. Roberto Weigert at the National Institute of Dental and Craniofacial Research, where she specialized in intravital microscopy to study mitochondrial dynamics in salivary glands, work that was recognized with an NIH Pathway to Independence (K99/R00) Award.

Since establishing her own group at NCI in 2018, Dr. Porat-Shliom has developed integrated molecular, biochemical, and imaging platforms to dissect liver zonation, nutrient sensing, and mitochondrial remodeling in normal tissue, metabolic dysfunction-associated steatotic liver disease, and liver cancer, with the goal of understanding tumor heterogeneity. She is the chair of the NCI Women's Science Advisor Committee, serves on the editorial board of Cancer Prevention Research, and is actively involved in mentoring and career-development programs for early-career scientists.