Timothy A. Ryan

This study identifies NDK as a key gene at the intersection of guanosine nucleotide metabolism and bioenergetics, showing its protective role in Parkinson's disease and its association with genetic risk.

The paper develops a ratiometric ER calcium sensor to enable quantitative comparisons of ER Ca2+ levels across cell types and subcellular regions, showing lower resting Ca2+ in neurons compared to fibroblasts.

The paper develops and validates a genetically encoded fluorescent sensor, iG6PSnFR, for measuring glucose-6-phosphate dynamics across multiple biological contexts.

This study shows that dopamine auto receptors regulate glycogen storage in midbrain dopaminergic neurons, linking neuromodulation to metabolic resilience and vulnerability in Parkinson's disease.

The paper shows that DDHD2 is essential for neurons to use fatty acids from lipid droplets as an energy source during activity when glucose is unavailable.

This paper identifies SLC13A5 as a genetic driver of epileptic encephalopathy that regulates presynaptic glycolysis by clearing axonal citrate during electrical activity.

The paper identifies periodic ER-PM junctions in dendrites that enable long-range Ca2+ signal integration through local spine activation and ryanodine receptor-dependent Ca2+ release.

The paper identifies PGK1 as a rate-limiting enzyme in axonal metabolism and shows its protective role against Parkinson's disease-related synaptic deficits.

This study shows that β-hydroxybutyrate supports neurotransmission in both excitatory and inhibitory neurons through cell-autonomous mitochondrial metabolism, with differential ATP levels and kinetics compared to lactate/pyruvate.

The paper identifies differences in mitochondrial function between inhibitory and excitatory neurons, showing inhibitory terminals have higher ATP levels and distinct Ca2+ handling mechanisms.

The paper reveals a non-linear relationship between action potential-driven Ca2+ influx and external Ca2+ concentration, showing neuromodulators can silence nerve terminals at physiological [Ca2+]e levels.

The paper shows that synaptic vesicle pools contribute significantly to resting metabolic demand in nerve terminals through V-ATPase activity driven by H+ efflux.

The paper shows that axonal mitochondria use MICU3 to adjust Ca2+ uptake sensitivity, enabling metabolic flexibility in neurotransmission under varying fuel conditions.