Bio
Frederick “Eric” Arnold obtained his PhD from Thomas Jefferson University under the mentorship of Dr. Diane Merry, where he studied the cellular mechanisms underlying polyglutamine-expanded androgen receptor toxicity in spinal and bulbar muscular atrophy (SBMA). He then joined the lab of Dr. Albert La Spada as a postdoc at Duke University then, following a lab relocation, at UC Irvine. During his postdoctoral work, Eric studied TDP-43 biology in amyotrophic lateral sclerosis (ALS) and characterized novel genetic variants associated with neurological disease. Eric established his lab in the Department of Genetics at Washington University in St. Louis in 2025.
Research
The Arnold Lab is broadly focused on studying the molecular mechanisms underlying neuronal loss in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other TDP-43 proteinopathies, as well as identifying new biomarkers and therapeutic targets for these disorders.
The majority of neurodegenerative disease is ‘sporadic,’ caused by poorly understood interactions between genetic and environmental risk factors; however, there are common pathological features that link some of these disorders. One such hallmark is the nuclear clearance and cytoplasmic aggregation of TDP-43, which is observed in 97% of patients with ALS, 50% of FTD patients, and approximately 50% of Alzheimer’s disease (AD) patients. Together, the neurodegenerative disorders characterized by TDP-43 pathology are referred to as ‘TDP-43 proteinopathies.’ Therapies that slow or reverse TDP-43 dysfunction thus have the potential to impact a broad group of neurogenerative disease patients; however, the mechanism by which TDP-43 mislocalization causes neuronal death remains incompletely understood, and modifiers of TDP-43 pathology are lacking.
To address these challenges, we study both the downstream consequences of TDP-43 dysfunction, as well as upstream modifiers of TDP-43 pathology. Our work includes biomarker development using targeted proteomics in patient tissue and biofluids, functional assays in iPSC-derived neuron models, and genome engineering to generate new cell models of TDP-43 proteinopathy.
Selected Publications
Arnold, F. J., Cui, Y., Michels, S., Colwin, M. R., Stockford, C., Wenbin, Y., Tam, O. H., Menon, S., Situ, W. G., Ehsani, K. C. K., Howard, S., Hammell, M. G., Li, W., La Spada, A. R. TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in ALS/FTD. J Clin Invest 2025, 135(11). PMID: 40454469
Cui, Y.*, Arnold, F. J.*, Li, J. S., Wu, J., Wang, D., Philippe, J., Colwin, M. R., Michels, S., Chen, C., Sallam, T., Thompson, L. M., La Spada, A. R., Li, W. Multi-omic quantitative trait loci link tandem repeat size variation to gene regulation in human brain. Nature Genetics. 2025, 57(2): 368-378. PMID: 39809899
Arnold, F. J., Putka, A. F., Raychaudhuri, U., Hsu, S., Bedlack, R. S., Bennett, C. L., La Spada, A. R. Revisiting glutamate excitotoxicity in amyotrophic lateral sclerosis and age-related neurodegeneration. International Journal of Molecular Sciences. 2024, 25(11). PMID: 38891774
DeBartolo, D.*, Arnold, F. J.*, Liu, Y., Molotsky, E., Tang, H.-Y., Merry, D. E. Differentially disrupted spinal cord and muscle energy metabolism in spinal and bulbar muscular atrophy. JCI Insight. 2024;9(7):e178048. PMID: 38452174
Arnold, F. J., Chiu, Y., Burns, M., Carvalho, J., Nguyen, A. D., Ralph, P., La Spada, A. R., Bennet, C. L. Chronic BMAA exposure combined with TDP-43 mutation elicits motor neuron dysfunction phenotypes in mice. Neurobiology of Aging, 2023. 126:44-57. PMID: 36931113
Cui, Y.*, Arnold, F. J.*, Peng, F., Wang, D., Li, J. S., Michels, S.,Wagner E. J., La Spada, A. R., Li, W. Alternative polyadenylation transcriptome-wide association study identifies APA-linked susceptibility genes in brain disorders. Nature Communications2023, 14 (1), 583. PMID: 36737438
Arnold F. J., Merry DE. Molecular Mechanisms and Therapeutics for SBMA/Kennedy’s Disease. Neurotherapeutics. 2019;16(4):928-47. PMID: 31686397
Arnold, F. J., Pluciennik, A., Merry, D. E. Impaired nuclear export of polyglutamine-expanded androgen receptor contributes to toxicity in spinal and bulbar muscular atrophy. Scientific Reports, 2019;9(1):119. PMID: 30644418
Education
2008-2012 BS, Biology, Haverford College (Advisor: Dr. Rachel Hoang)
2012-2019 PhD, Thomas Jefferson University (Advisor: Dr. Diane Merry)
2019-2024 Postdoctoral Fellow, University of California Irvine (Advisor: Dr. Albert La Spada)
Selected Honors
2024 Barber ALS Research Award
2023 Target ALS Springboard Fellowship
2022 Richard Olney Clinician Scientist Development Award in ALS
2019 The Fredric Rieders Foundation Graduate Student Recognition Award