Research

The organization and architecture of cells must be precisely regulated to enable tissues to develop, function, and regenerate. While most people are familiar with cell division, in which one cell splits to generate two daughter cells, biology also employs a strikingly opposite strategy: cell–cell fusion.

During cell–cell fusion, two individual cells combine their membranes and cytoplasm to form a single multinucleated cell. This process plays essential roles in diverse physiological and pathological contexts, including fertilization (egg–sperm fusion), placenta formation (trophoblast fusion), skeletal muscle development and regeneration (myoblast fusion), immune response (macrophage fusion), bone remodeling (osteoclast fusion), viral transmission (such as SARS-CoV-2 spreads) and cancer progression (cancer cell–macrophage fusion). 

Using skeletal muscle as our primary model system, we seek to understand the mechanisms that allow cells to overcome the energetic and structural barriers to merge their plasma membranes, and transition into functional syncytia. 

To do so, we use a multidisciplinary approach including:

  • Advanced microscopies: high-resolution live-cell imaging, super-resolution microscopy and electron microscopy
  • Cell biology
  • Biochemistry
  • Mouse genetics

 

Current Research

Our current research centers on the following directions:

  • Metabolic control of cell–cell fusion: fueling membrane merger

Cell–cell fusion is a metabolically demanding process. To merge two distinct plasma membranes into one, the fusion machinery requires substantial energy and biosynthetic inputs to support the extensive remodeling of actin networks, the activation of fusogens, and the membrane lipid mixing. We are particularly interested in understanding the energy provisioning mechanisms that fuel the fusion machinery. This work will not only provide a roadmap for how metabolic circuits are wired to support the energetically demanding process of cell–cell fusion, but also establish a new paradigm in which temporally and spatially organized metabolism drives morphogenetic behaviors across diverse biological systems during tissue development, homeostasis, and disease. 

  • Fusion brakes: restricting and fine-tuning cell–cell fusion

While cell–cell fusion is essential for normal development and regeneration, ectopic fusion can have pathological consequences. Despite these implications, the field has largely focused on pro-fusion mechanisms. We seek to identify the endogenous inhibitors that restrict or fine-tune cell fusion. This project will help us understand how cells limit membrane merger in physiological and pathological contexts and open the door to therapeutic targets for diseases driven by excessive or misdirected membrane fusion.

  • Post-fusion integration: building functional syncytia

After membrane merger, cells must reorganize their internal architecture to form a functional syncytium. How two previously independent cells integrate their cytoplasmic contents and subcellular systems to establish a coordinated and functional cellular unit remains poorly understood. We are interested in understanding how organelles and cytoskeletal systems from two fusion partners integrate following fusion pore expansion. These events are essential for establishing coordinated metabolism, intracellular transport, and signaling within the newly formed syncytium. By dissecting the mechanisms that govern post-fusion integration, we aim to uncover fundamental principles by which cells reorganize their internal architecture to build functional tissues.