Jeffrey Milbrandt

Mitochondrial NAD+ import gates neuronal resilience to active SARM1

This study shows that enhancing mitochondrial NAD+ import through SLC25A51 protects neurons from SARM1-driven degeneration by preventing coupled metabolic failure.

Dysregulated lactate metabolism synergizes with ALS genetic risk factors to accelerate motor decline

The paper investigates how partial disruption of lactate metabolism, specifically through LDHB loss, synergizes with ALS genetic risk factors to accelerate motor decline.

TDP-43 suppression of ATP8A2 cryptic splicing implicates phosphatidylserine-driven neuroinflammation in ALS/FTD

This study identifies ATP8A2 as a TDP-43 target whose loss leads to PS exposure and neuroinflammation, suggesting immune cell inhibition as a therapeutic strategy for ALS-FTD and CAMRQ4.

Whole-Genome Sequencing Reveals Individual and Cohort Level Insights into Chromosome 9p Syndromes

This study uses whole-genome sequencing to analyze 9p deletion and duplication syndromes, identifying key genes and structural variants, and introduces a machine learning model for syndrome prediction.

Pathogenic Morphological Signatures of Perturbations in Mitochondrial-Related Genes Revealed by Pooled Imaging Assay

The paper identifies mitochondrial-related genes critical for morphology using a pooled imaging assay and reveals pathogenic variants associated with mitochondrial aggregation.

SARM1 is an essential component of neuronal Parthanatos

This study shows SARM1 is essential for neuronal Parthanatos, a cell death pathway triggered by DNA damage and linked to neurodegenerative diseases.

Suppressing phagocyte activation by overexpressing the phosphatidylserine lipase ABHD12 preserves sarmopathic nerves

The paper shows that overexpressing ABHD12 in neurons reduces macrophage activation and preserves axon integrity in a sarmopathy model by modulating phosphatidylserine levels.

Heterozygous and Homozygous RFC1 AAGGG Repeat Expansions are Common in Idiopathic Peripheral Neuropathy

The paper identifies RFC1 AAGGG repeat expansions in idiopathic peripheral neuropathy patients using a new computational pipeline and finds both heterozygous and homozygous expansions contribute to the condition.

Biophysical Simulation Enables Multi-Scale Segmentation and Atlas Mapping for Top-Down Spatial Omics of the Nervous System

SiDoLa-NS uses synthetic images and multi-scale CNNs to achieve high-precision segmentation of nuclei and tissue structures in nervous system samples.

The response of Dual-Leucine Zipper Kinase (DLK) to nocodazole: evidence for a homeostatic cytoskeletal repair mechanism

This study shows that DLK signaling is activated by low-dose nocodazole and mitigates microtubule damage, revealing a cytoskeletal homeostatic response pathway in neurons.

Reduced STMN2 and pathogenic TDP-43, two hallmarks of ALS, synergize to accelerate motor decline in mice

This study shows that reduced STMN2 and pathogenic TDP-43 synergize to accelerate motor decline in mice without detectable neuropathology but with mitochondrial abnormalities.

Macrophage depletion blocks congenital SARM1-dependent neuropathy

This study shows that macrophage depletion reverses neuropathic symptoms in a mouse model of SARM1-dependent neuropathy caused by NMNAT2 variants.

Defining hierarchical protein interaction networks from spectral analysis of bacterial proteomes

This paper introduces SCALES, a method that extracts hierarchical protein interaction networks from bacterial proteome variation patterns, revealing new genetic factors in Pseudomonas aeruginosa motility.

Measuring transcription factor binding and gene expression using barcoded self-reporting transposon calling cards and transcriptomes

This paper introduces barcoded self-reporting transposon calling cards to efficiently measure transcription factor binding and gene expression in bulk populations, demonstrating their use in vitro and in vivo.

Disruption of lactate metabolism in the peripheral nervous system leads to motor-selective deficits

This study shows that disrupting lactate metabolism in Schwann cells or motor neurons causes motor axon degeneration, while sensory axons remain unaffected, highlighting a specific dependency of motor axons on lactate shuttling.

Loss of Stathmin-2, a hallmark of TDP-43-associated ALS, causes motor neuropathy

This study shows that loss of STMN2, linked to TDP-43 pathology in ALS, causes motor neuropathy with NMJ denervation in mice.

SARM1 promotes axonal, synaptic, and mitochondrial pathologies in Charcot-Marie-Tooth disease type 2A

This study shows that SARM1 inhibition reduces axonal, synaptic, and mitochondrial defects in a CMT2A rat model.

Constitutively active SARM1 variants found in ALS patients induce neuropathy

The paper identifies constitutively active SARM1 variants in ALS patients that induce neuropathy and neuroinflammation in mice.

Activation of Sarm1 produces cADPR to increase intra-axonal calcium and promote axon degeneration in CIPN

This study shows that paclitaxel induces cADPR production via Sarm1, increasing intra-axonal calcium and causing axon degeneration, with cADPR antagonists preventing neuropathy without affecting chemotherapy efficacy.

Live Imaging Reveals the Cellular Events Downstream of SARM1 Activation

This study uses live imaging to show that SARM1 activation leads to a sequence of cellular events starting with ATP loss and ending in axonal self-destruction.

Neurotoxins subvert the allosteric activation mechanism of SARM1 to induce neuronal loss

This study identifies neurotoxins that activate SARM1 by binding to its allosteric site, leading to NAD+ depletion and neuronal death.

Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection

The paper identifies nicotinic acid mononucleotide (NaMN) as an allosteric inhibitor of SARM1 that promotes axonal protection by blocking NMN binding and stabilizing the inactive SARM1 conformation.

Mitochondrial Phenotypes Distinguish Pathogenic MFN2 Mutations by Pooled Functional Genomics Screen

The paper introduces Raft-Seq, a functional genomics platform that distinguishes pathogenic MFN2 mutations using high-content imaging, machine learning, and microraft isolation.

SARM1 depletion rescues NMNAT1 dependent photoreceptor cell death and retinal degeneration.

This study shows that SARM1 depletion prevents NMNAT1-dependent photoreceptor death and retinal degeneration in mice, identifying SARM1 as a therapeutic target for retinopathies.

High-throughput single-cell functional elucidation of neurodevelopmental disease-associated genes reveals convergent mechanisms altering neuronal differentiation

This paper uses single-cell profiling to functionally analyze ASD genes, identifying two convergent modules affecting neuronal differentiation and predicting shared clinical phenotypes.

Single cell RNAseq uncovers a robust transcriptional response to morphine by oligodendrocytes

This study identifies morphine-induced gene expression changes in oligodendrocytes using single-cell RNA sequencing in mice, highlighting pathways related to myelination.