ana Paula arruda

Ana Paula Arruda, PhD, Assistant Professor, Department of Metabolic Biology and Nutrition, University of California, Berkeley

Research Description: Our laboratory investigates how the architecture and function of intracellular organelles shape metabolic homeostasis and contribute to the development of chronic metabolic diseases such as diabetes and fatty liver disease. We focus particularly on the endoplasmic reticulum (ER), a dynamic membrane network that coordinates many processes essential for metabolic health, including protein synthesis and folding, lipid biosynthesis, glucose metabolism, calcium homeostasis, and communication between organelles. In metabolically active tissues such as the liver, the ER continuously remodels its organization of sheets, tubules, and organelle contact sites in response to changes in nutrient availability. We have found that chronic metabolic stress associated with obesity profoundly disrupts this organization, causing a loss of ER sheets and expansion of ER tubules. These structural changes are accompanied by impaired protein-folding capacity, dysregulated lipid metabolism, hepatic steatosis, cellular stress, and insulin resistance. Our work seeks to understand whether and how failure of organelle architecture to appropriately adapt to metabolic stress contributes to the transition from metabolic homeostasis to diabetes.

To address these questions, we integrate high-resolution three-dimensional ultrastructural and fluorescence imaging, including focused ion beam scanning electron microscopy (FIB-SEM) and super-resolution lattice structured illumination microscopy (lattice-SIM), with molecular, biochemical, and physiological approaches. Using mouse models of obesity, insulin resistance, diabetes, and fatty liver disease, we connect changes in organelle architecture across spatial scales with metabolic function and disease progression. Ultimately, our research aims to uncover fundamental principles linking intracellular architecture to metabolic control and identify new mechanisms that can be targeted to prevent or reverse metabolic disease.

Selected relevant publications (SDRC members in BOLD):

  1. Mathiowetz AJ, Meymand ES, Parlakgül G, van Hilten N, Torres EF, Artico LL, Deol KK, Lange M, Pang SP, Doubravsky, CE, Roberts MA, Jorgens DM, Zalpuri R, Kang M, Boone C, Parks BW, Zhang Y, Morgens DW, Newman ET, Zhou Y, Talukdar S, Grabe M, Ku G, Levine TP, Arruda AP, Olzmann JA. CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly. Nature. 2026 Apr;652(8109):462-470. PubMed Central PMCID: PMC13061601.

  2. Parlakgül G, Pang S, Artico LL, Min N, Cagampan E, Villa R, Goncalves RLS, Lee GY, Xu CS, Hotamışlıgil GS, Arruda AP. Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity. Nat Commun. 2024 May 10;15(1):3982. PubMed Central PMCID: PMC11087507.

  3. Arruda AP, Parlakgül G. Endoplasmic Reticulum Architecture and Inter-Organelle Communication in Metabolic Health and Disease. Cold Spring Harb Perspect Biol. 2023 Feb 1;15(2) PubMed Central PMCID: PMC9899651.