Hoang Minh Hieu Nguyen

All Publications

• PI31 expression is neuroprotective in a mouse model of early- onset parkinsonism PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rodriguez, J. A., Minis, A., Aref, R., Nguyen, H., Sun, F., Steller, H., Chao, M. 2025; 122 (38): e2511899122

  Abstract

  Neurodegenerative diseases present one of the most significant global health challenges. These disorders are defined by the accumulation of abnormal protein aggregates that impair synaptic function and cause progressive neuronal degeneration. Therefore, stimulating protein clearance mechanisms may be neuro-protective. Variants in FBXO7/PARK15 cause Parkinsonian Pyramidal Syndrome, an early-onset parkinsonian neurodegenerative disorder in humans, and inactivation of this gene in mice recapitulates many phenotypes seen in patients. The proteasome regulator PI31 is a direct binding partner of Fbxo7 and promotes local protein degradation at synapses by mediating fast proteasome transport in neurites. PI31 protein levels are reduced when the function of Fbxo7 is impaired. Here we show that restoring PI31 levels in Fbxo7 mutant fly and mouse strains prevents neuronal degeneration and significantly improves neuronal function, health, and lifespan. Notably, Fbxo7 inactivation in mouse neurons causes hyperphosphorylation of tau, and this was suppressed by transgenic expression of PI31. Our results demonstrate that PI31 is a crucial biological target through which Fbxo7 deficiency drives pathology. Therefore, targeting the PI31-pathway may represent a promising therapeutic approach for treating neurodegenerative disorders.

  View details for DOI 10.1073/pnas.2511899122

  View details for Web of Science ID 001585678100001

  View details for PubMedID 40956890

  View details for PubMedCentralID PMC12478140

• Effects of Testosterone and Its Major Metabolites upon Different Stages of Neuron Survival in the Dentate Gyrus of Male Rats. Biomolecules Spritzer, M. D., Roy, E. A., Calhoun, K. M., Schneider-Lynch, Z. E., Panella, L., Michaelcheck, C., Qian, A., Kelly, E. D., Barr, H., Hall, E., Cunningham, B., Nguyen, H. H., Xu, D., Barker, J. M., Galea, L. A. 2025; 15 (4)

  Abstract

  Testosterone has been shown to enhance hippocampal neurogenesis through increased cell survival, but which stages of new neuron development are influenced by testosterone remains unclear. Therefore, we tested the effects of sex steroids administered during three different periods after cell division in the dentate gyrus of adult male rats to determine when they influence the survival of new neurons. Adult male rats were bilaterally castrated. After 7 days of recovery, a single injection of bromodeoxyuridine (BrdU) was given on the first day of the experiment (Day 0) to label actively dividing cells. All subjects received five consecutive days of hormone injections during one of three stages of new neuron development (days 1-5, 6-10, or 11-15) after BrdU labeling. Subjects were injected during these time periods with either testosterone propionate (0.250 or 0.500 mg/rat), dihydrotestosterone (0.250 or 0.500 mg/rat), or estradiol benzoate (1.0 or 10 µg/rat). All subjects were euthanized sixteen days later to assess the effects of these hormones on the number of BrdU-labeled cells. The high dose of testosterone caused a significant increase in the number of BrdU-labeled cells in the hippocampus compared to all other groups, with the strongest effect caused by later injections (11-15 days old). In contrast, neither DHT nor estradiol injections had any significant effects on number of BrdU-labeled cells. Fluorescent double-labeling and confocal microscopy reveal that the majority of BrdU-labeled cells were neurons. Our results add to past evidence that testosterone increases neurogenesis, but whether this involves an androgenic or estrogenic pathway remains unclear.

  View details for DOI 10.3390/biom15040542

  View details for PubMedID 40305218

  View details for PubMedCentralID PMC12024780

• Engineered extrachromosomal oncogene amplifications promote tumorigenesis. Nature Pradella, D., Zhang, M., Gao, R., Yao, M. A., Gluchowska, K. M., Cendon-Florez, Y., Mishra, T., La Rocca, G., Weigl, M., Jiao, Z., Nguyen, H. H., Lisi, M., Ozimek, M. M., Mastroleo, C., Chen, K., Grimm, F., Luebeck, J., Zhang, S., Zolli, A. A., Sun, E. G., Dameracharla, B., Zhao, Z., Pritykin, Y., Sigel, C., Chang, H. Y., Mischel, P. S., Bafna, V., Antonescu, C. R., Ventura, A. 2024

  Abstract

  Focal gene amplifications are among the most common cancer-associated mutations1 but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs)2 in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures. We also apply this approach to generate mice harbouring Cre-inducible Myc- and Mdm2-containing ecDNAs analogous to those occurring in human cancers. We show that the engineered ecDNAs spontaneously accumulate in primary cells derived from these animals, promoting their proliferation, immortalization and transformation. Finally, we demonstrate the ability of Mdm2-containing ecDNAs to promote tumour formation in an autochthonous mouse model of hepatocellular carcinoma. These findings offer insights into the role of ecDNA-mediated gene amplifications in tumorigenesis. We anticipate that this approach will be valuable for investigating further unresolved aspects of ecDNA biology and for developing new preclinical immunocompetent mouse models of human cancers harbouring specific focal gene amplifications.

  View details for DOI 10.1038/s41586-024-08318-8

  View details for PubMedID 39695225

  View details for PubMedCentralID 2826709