Haoyu Xu
BME PhD Proposal Presentation

Date: 2025-06-06
Time: 11:00 AM
Location / Meeting Link: EBB Krone 3029

Committee Members:
Marcus Cicerone, PhD(advisor); Shu Jia, PhD; Ahmet Coskun, PhD; Francisco E Robles, PhD; Shinichi Someya, PhD


Title: Multimodal BCARS-FLIM Imaging of Mitochondrial Structure–Metabolism Relationships in Mouse Cochlear Hair Cells

Abstract:
Hearing loss affects over 466 million people worldwide, often resulting from damage to cochlear hair cells that depend on mitochondria for energy production and synaptic function. While mitochondrial structural changes like fragmentation and redistribution correlate with metabolic dysfunction, the precise relationship between mitochondrial morphology and metabolic state in hair cells remains unclear due to limitations of current imaging approaches. We propose developing a novel multimodal imaging platform combining Fluorescence Lifetime Imaging Microscopy (FLIM) and Broadband Coherent Anti-Stokes Raman Scattering (BCARS) to simultaneously measure mitochondrial structure and metabolism in mouse cochlear hair cells. First, we will engineer a co-registered FLIM-BCARS system optimized for fixed cochlear tissue, enabling simultaneous acquisition of NAD(P)H redox lifetimes and biochemical signatures at subcellular resolution. We will then establish comprehensive 3D morphometric analysis of mitochondrial networks and ribbon synapses across cochlear frequency regions and between sexes using existing confocal datasets, providing spatial context for metabolic correlations. Finally, we will apply the multimodal platform to correlate mitochondrial structure with metabolic state under conditions that enhance (physical activity) or impair (cisplatin treatment) mitochondrial function. We expect to demonstrate that mitochondrial fragmentation correlates with reduced NAD(P)H binding efficiency and altered biochemical signatures. This work will establish the first FLIM-BCARS application in cochlear research and identify early metabolic biomarkers of hearing loss that precede structural damage, potentially enabling therapeutic intervention before irreversible cochlear dysfunction occurs.