Novel Imaging Biomarkers

Advancing Precision Medicine through Imaging, Lipidomics, and AI

Our research group investigates the role of cellular membranes in health and disease, aiming to develop novel biomarkers and therapeutic strategies for precision medicine. We utilize advanced imaging techniques, lipidomics, and artificial intelligence to study membrane fluidity, lipid composition, oxidative stress, and autophagy. Our goal is to translate these findings into clinically relevant applications.

Featured Research Areas:

The Cellular Membrane as the Central Regulator of Life and Disease

Redox imaging and oxidative stress in cells

Autophagy, cellular morphodynamics and intracellular signaling

Membrane Fluidity and Lipid Modulation

in Red Blood Cells:
From Physics to Clinical Biomarkers

Red blood cells (RBCs) are traditionally known for their role in gas transport, but recent advances have positioned them as dynamic reporters of metabolic health. Their plasma membrane, composed of a lipid bilayer with embedded proteins, is sensitive to oxidative stress, fatty acid composition, and pathological conditions—especially in diabetes.

Lipid-Driven Modulation of Membrane Fluidity

Membrane fluidity is determined largely by its lipid composition, particularly the ratio of saturated to unsaturated fatty acids and cholesterol content. Alterations in this composition—due to diet, inflammation, or metabolic disorders—directly affect the biophysical behavior of membranes. In our study we demonstrated how fatty acid remodeling influences membrane properties in a range of cell types. These changes can:

Modify the liquid-crystalline phase of membranesAlter the spatial organization of lipid rafts
Affect key signaling processes and protein-lipid interactions

This lipid-centric perspective forms the biophysical foundation for our translational work on RBC membranes.

Biophysics Meets Clinical Diagnostics

We applied this understanding to investigate erythrocyte membrane fluidity in patients with metabolic diseases.

Together, these works define a new diagnostic paradigm: erythrocyte membrane fluidity, shaped by underlying lipid dynamics, acts as a sensitive and quantifiable marker of metabolic and vascular status.

Redox Signaling and Oxidative Stress:
A Functional Layer of Membrane Biology

Oxidative stress is a key driver of cellular dysfunction and disease progression, especially in metabolic and neurodegenerative conditions. Despite its importance, quantifying redox imbalance in living cells with high spatial and temporal resolution has remained a major challenge.

Our research group has addressed this by developing real-time, quantitative imaging methods that allow intracellular mapping of oxidative stress at subcellular resolution—paving the way for redox biology to be incorporated into diagnostic frameworks.

Cochlea

We studied the outer hair cells of the cochlea exposed to noise-induced stress. Here, we observed how redox imbalance:

Triggers lipid peroxidation
Reduces membrane fluidity
Ultimately leads to functional and structural damage

These findings represent a direct link between oxidative stress, membrane biophysics, and cellular degeneration—especially in sensory systems highly vulnerable to redox perturbations.

Longitudinal distribution of NAD(P)H and fluidity in OHC cells	Time-course response of cochlear outer hair cells to acoustic stress
Zoom-In on Local Damage in Outer Hair Cells (OHCs)	Mechanistic Model and Quantitative Validation

Click on the images below for more information

We applied FRIM to assess the glutathione redox state in live cells. By using ratiometric probes like monochlorobimane (MCB) and roGFP-based sensors, we quantified:

The GSH/GSSG ratio at organelle level

Spatial gradients in oxidative stress responses

Temporal dynamics under stress-inducing stimuli

This method allowed us to generate "redox maps", offering insight into how different cellular compartments experience oxidative imbalance differently—something not possible with bulk biochemical assays.

Autophagy, cellular morphodynamics
and intracellular signaling

Cells are not static entities. Their shape, internal organization, and dynamic processes are constantly adapting in response to external and internal cues. This plasticity is essential for survival, stress response, and metabolic regulation. Our research explores how to quantify these intracellular dynamics, with a particular focus on autophagic flux, morphodynamics, and their links to cellular signaling.

Quantifying Autophagy in Real Time

Autophagy is a fundamental catabolic process where cells recycle damaged components and respond to metabolic stress. Traditional methods to monitor it (e.g., LC3 immunostaining) often lack temporal resolution and

quantitativeness.

We developed a confocal pH-sensitive imaging protocol to quantitatively monitor autophagic flux: We used fluorescent probes that change emission based on pH, enabling us to distinguish between autophagosomes (neutral pH) and autolysosomes (acidic pH). The technique allows live tracking of autophagic intermediates over time, capturing dynamic transitions.

Reveal the pH inside autophagic organelles by pointing over each cell image.

Blue/Purple areas → acidic vesicles

Yellow/Red areas → less acidic or neutral vesicles

Homogeneous signal, few acidic structures — typical of basal autophagy.

Control: Cells under normal conditions

Slightly less intense, resembling control more closely.

Combined nutrient deprivation and rapamycin treatment

Strong activation of autophagy, with many acidic structures.

Starvation: Cells deprived of nutrients to trigger autophagy

Increased number of acidic vesicles (violet), indicating autolysosome formation and enhanced autophagic flux

Rapamycin: Cells treated with rapamycin, a drug that promotes autophagy

Accumulation of neutral vesicles — autophagy is blocked

Chloroquine: An inhibitor that blocks the fusion between autophagosomes and lysosomes

Few vesicles overall — early autophagy is inhibited.

3-Methyladenine: A compound that prevents the formation of new autophagosomes

Stochastic Morphodynamics and Signal Integration

We introduced a stochastic analysis framework that links cellular morphodynamics (changes in shape and edge fluctuation) with biochemical signaling events. Using time-lapse fluorescent imaging and edge-tracking algorithms, we modeled how the probability distribution of shape fluctuations changes under different stimuli.We demonstrated that morphological variability correlates with intracellular signaling noise, suggesting that shape is both a readout and regulator of signaling dynamics.

📊 Key impact: This approach offers a quantitative link between structure and signaling, moving beyond static imaging to capture cell behavior as a dynamic system.

Redox Dynamics and Membrane Signaling

In [📄 Science Signaling, 2008 – scisignal.143pl3.pdf], we detailed a protocol for quantifying redox changes in membranes using live-cell microscopy. These shifts in redox state are early indicators of:

Oxidative damage

Mitochondrial dysfunction

Signal transduction abnormalities

By integrating these measures with morphodynamic and pH imaging, we build a multi-parametric map of cell state transitions.