Funai Lab

Research Overview

Since 2013, my laboratory has been interested in the intracellular fate of lipids into membrane phospholipids and how they affect cellular metabolism. This was driven by my curiosity in understanding how lipids mediate obesity-driven metabolic diseases.

We have studied and published on ER and plasma membrane phospholipids, but we have extensively published and developed reputation on understanding how mitochondrial membrane phospholipids influence bioenergetics to alter propensity for metabolic diseases. In this line of work, we have been examining how mitochondrial membrane lipids alter with changes in energy supply or demand in different tissues, and implicate their roles in bioenergetics and metabolic physiology.

  • ER Phospholipids Research
    Funai et al., JCI, 2013; Paran et al., Obesity, 2015; Funai et al., Diabetes, 2016; Verkerke et al., Nature Metabolism, 2019
  • Plasma Membrane Phospholipids Research
    Ferrera et al., JCI, 2021; Ferrera et al., FASEB J, 2021
  • Mitochondrial Membrane Phospholipids & Bioenergetics
    Heden et al., Trends Endo Metab, 2016; Johnson et al., J Mol Cell Cardiol, 2018; Heden et al., Science Advances, 2019; Johnson et al., Mol Metab, 2020; Funai et al., Curr Opin Cell Biol, 2020; Johnson et al., Science Advances, 2023; Ferrara et al., Life Metab, 2023; Siripoksup et al., JCI, 2024; Decker et al., Cell Metabolism, 2024; Brothwell et al., eLife, 2025

Current Research Directions

As described below, our lab continues to work in this area with new emphasis in addressing more fundamental and mechanistic questions for how mitochondrial lipids influence bioenergetics. We have two additional major lines of research in my laboratory:

  • The role that lipid peroxidation plays in skeletal muscle mass and function
  • The mechanisms and physiological implications that drive an increase in mitochondrial energy efficiency after weight loss

All of these topics synergize with our expertise and interests in mitochondrial bioenergetics, lipid metabolism, endocrinology, exercise physiology, skeletal muscle biology, and mass spectrometry.

We are also expanding our research beyond understanding the mechanisms and have started or are in the process of starting clinical studies/trials to test our findings in humans.

Current Research Areas

Mitochondrial Membrane Lipids and Energy Flux through OXPHOS

We investigate how specific mitochondrial membrane lipids regulate energy production through oxidative phosphorylation. Using advanced techniques like high-resolution respirometry and super-resolution microscopy, we identify which exact energy-transducing steps are controlled by lipids like cardiolipin and phosphatidylethanolamine in various tissues and disease states.

Lipid Peroxidation and Carbonyl Stress

We study how lipid peroxidation contributes to muscle decline in aging, disuse, and cancer. Our work focuses on carnosine compounds that neutralize toxic lipid byproducts, with ongoing clinical trials testing these safe nutraceuticals. We've developed novel mass spectrometry methods to map protein damage caused by lipid peroxidation.

Semaglutide-Induced Weight Loss and Skeletal Muscle Mitochondrial Energy Efficiency

We discovered that both dietary and semaglutide-induced weight loss make skeletal muscle mitochondria more energy efficient, producing more ATP with less oxygen. This may explain reduced energy expenditure after weight loss. We're now investigating the mechanisms behind this efficiency shift and conducting human studies to understand its clinical implications.