Unraveling the Molecular Machinery of Sperm Development

Each day, millions of sperm are produced in the testis through spermiogenesis—a dramatic transformation in which round, haploid spermatids reshape into elongated, motile sperm. This process involves nuclear compaction, cytoplasmic shedding, and flagellum formation—yet the molecular mechanisms driving these changes remain one of the most intriguing mysteries in reproductive cell biology.

Our lab recently identified a novel membrane protein that is essential for this process. Mice lacking this protein are healthy but completely infertile, producing no sperm due to arrested spermatid elongation. Importantly, the human counterpart of this protein is also highly enriched in spermatids and sperm, and has been linked to cases of non-obstructive azoospermia—a condition affecting nearly 1 in 5 infertile men.

Intriguingly, this protein shares structural and functional features with a well-known mechanosensitive ion channel found in inner ear sensory cells. That protein is known to mediate calcium influx, regulate actin-based protrusions, and flip membrane lipids—functions critical to shaping and sensing cellular architecture. Early data from our lab suggest that this testis-enriched membrane protein may perform similar roles in spermatids, coupling lipid redistribution, F-actin remodeling, and calcium signaling during sperm morphogenesis.

Why is this excitingt?

• Tackle a fundamental question in reproductive biology: how do cells remodel themselves so drastically to become sperm?

• Use cutting-edge techniques: CRISPR-based genetic models, super-resolution and electron microscopy, live-cell calcium imaging, and lipid/protein interactomics.

• Be part of discovery-stage science, working on a protein with unpublished, high-impact potential.

• Contribute to translational goals: this protein is part of the “druggable proteome”, with implications for developing the first non-hormonal male contraceptive.

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  Current Projects

  1. Lipid Dynamics During Spermatid Elongation

  We discovered that developing spermatids transiently expose phosphatidylserine (PS) on their outer membranes—a surprising finding, since PS externalization is typically associated with apoptosis. Using advanced imaging and targeted inhibition strategies, we’re investigating how lipid scrambling contributes to membrane remodeling during elongation—and whether this novel protein is the key regulator.

  2. Cytoskeletal Remodeling and Shape Control

  Specialized F-actin structures guide elongation of spermatids, but how these networks are controlled remains poorly understood. By combining spermatogenesis synchronization with super-resolution microscopy and electron tomography, we are dissecting how cytoskeletal organization is altered when this protein is lost—and how it may control actin dynamics in vivo and in heterologous systems.

  3. Membrane Signaling Complexes and Calcium Regulation

  We hypothesize that this protein is part of a larger membrane complex that coordinates intracellular calcium responses. Preliminary data show it physically interacts with known calcium-binding proteins required for both hearing and spermatogenesis. Using interactomics and calcium imaging, we are uncovering how this signaling axis drives key steps in sperm development.