Darcie L. Moore, PhD

Position title: Associate Professor, Neuroscience

PhD, University of Miami

Contact Information

1111 Highland Avenue
Room 5505 WIMR-II
Madison, WI 53705
(608) 265-7836
darcie.moore@wisc.edu
Moore Lab Website

Research Statement

There is limited regenerative capacity in the adult mammalian central nervous system (CNS). My lab studies this loss of regeneration in two different contexts:

Adult neurogenesis, where neural stem cells (NSCs) make newborn neurons in the adult brain

CNS axon regeneration following an injury
Specifically we determine how changes during development and aging influence these aspects of regeneration.

Adult neurogenesis

NSCs in the hippocampus generate newborn neurons throughout life in a process referred to as adult neurogenesis. Adult NSCs are primarily quiescent, in a reversible G0 state. Upon receiving a signal, quiescent NSCs (qNSCs) activate, entering the cell cycle to initiate population expansion, differentiation, maturation, and integration. During aging and disease, extrinsic and intrinsic factors drive adult hippocampal NSCs deeper into quiescence, reducing NSC quiescence exit, ultimately contributing to cognitive decline.

My lab works to identify factors controlling NSC quiescence and quiescence exit to improve neurogenesis and ultimately identify targets to enhance cognitive function. We specifically have focused our efforts in the following areas: Proteostasis, translational control, asymmetric inheritance of specific cellular cargoes during mitosis, creation of imaging tools to identify qNSCs, how this translates to cancer.

CNS Axon Growth and Regeneration

Despite decades of study in rodent models, there is still no “cure” for CNS injuries such as spinal cord injury (SCI). The lack of human-specific and age-specific models of axon growth may be a crucial limiting factor in identifying translational targets for treatment of human SCI. Thus, we used direct reprogramming of human fibroblasts to neurons, bypassing pluripotency to maintain the age of the original cell, to create human neurons of different ages. We hypothesize that a species- and age-specific model will lead to the identification of axon growth regulators that could be targeted for development of more effective therapies for human SCI. Our research in this area has focused on: the developmental loss of intrinsic axon growth ability in human neurons, epigenetic regulation of axon growth and regeneration.

To address these questions, the Moore lab uses cell biology, biochemistry, molecular biology, genetics, and computational approaches. We also specifically focus on using advanced live imaging technologies, including FLIP, FLIM, FRAP, photoactivation, 4D timelapse, in vivo cranial window imaging, and computer learning-based high-throughput imaging to address our scientific questions.

Research Topics

Neural Development, Spinal Cord Injury, Stem Cells

Selected Publications

PubMed

Samimi, K., Pasachhe, O., Guzman, E. C., Riendeau, J., Gillette, A. A., Pham, D. L., Wiech, K. J., Moore, D. L., & Skala, M. C. (2024). Autofluorescence lifetime flow cytometry with time-correlated single photon counting. Cytometry. Part A : the journal of the International Society for Analytical Cytology, 105(8), 607–620. https://doi.org/10.1002/cyto.a.24883
Morrow, C. S., Tweed, K., Farhadova, S., Walsh, A. J., Lear, B. P., Roopra, A., Risgaard, R. D., Klosa, P. C., Arndt, Z. P., Peterson, E. R., Chi, M. M., Harris, A. G., Skala, M. C., & Moore, D. L. (2024). Autofluorescence is a biomarker of neural stem cell activation state. Cell stem cell, 31(4), 570–581.e7. https://doi.org/10.1016/j.stem.2024.02.011
Morrow, C. S., Gillette, A. A., Skala, M. C., & Moore, D. L. (2024). Classification of Neural Stem Cell Activation State In Vitro using Autofluorescence. Journal of visualized experiments : JoVE, (206), 10.3791/63110. https://doi.org/10.3791/63110
Souder, D. C., McGregor, E. R., Rhoads, T. W., Clark, J. P., Porter, T. J., Eliceiri, K., Moore, D. L., Puglielli, L., & Anderson, R. M. (2023). Mitochondrial regulator PGC-1a in neuronal metabolism and brain aging. bioRxiv : the preprint server for biology, 2023.09.29.559526. https://doi.org/10.1101/2023.09.29.559526
Scandella, V., Petrelli, F., Moore, D. L., Braun, S. M. G., & Knobloch, M. (2023). Neural stem cell metabolism revisited: a critical role for mitochondria. Trends in endocrinology and metabolism: TEM, 34(8), 446–461. https://doi.org/10.1016/j.tem.2023.05.008
Lear, B. P., & Moore, D. L. (2023). Moving CNS axon growth and regeneration research into human model systems. Frontiers in neuroscience, 17, 1198041. https://doi.org/10.3389/fnins.2023.1198041
Lear, B. P., Thompson, E. A. N., Rodriguez, K., Arndt, Z. P., Khullar, S., Klosa, P. C., Lu, R. J., Morrow, C. S., Risgaard, R., Peterson, E. R., Teefy, B. B., Bhattacharyya, A., Sousa, A. M. M., Wang, D., Benayoun, B. A., & Moore, D. L. (2023). Age-maintained human neurons demonstrate a developmental loss of intrinsic neurite growth ability. bioRxiv : the preprint server for biology, 2023.05.23.541995. https://doi.org/10.1101/2023.05.23.541995
Morrow, C. S., Arndt, Z. P., Klosa, P. C., Peng, B., Zewdie, E. Y., Benayoun, B. A., & Moore, D. L. (2022). Adult fibroblasts use aggresomes only in distinct cell-states. Scientific reports, 12(1), 15001. https://doi.org/10.1038/s41598-022-19055-1
Morrow, C. S., Porter, T. J., & Moore, D. L. (2021). Fluorescent tagging of endogenous proteins with CRISPR/Cas9 in primary mouse neural stem cells. STAR protocols, 2(3), 100744. https://doi.org/10.1016/j.xpro.2021.100744
Bin Imtiaz, M. K., Jaeger, B. N., Bottes, S., Machado, R. A. C., Vidmar, M., Moore, D. L., & Jessberger, S. (2021). Declining lamin B1 expression mediates age-dependent decreases of hippocampal stem cell activity. Cell stem cell, 28(5), 967–977.e8. https://doi.org/10.1016/j.stem.2021.01.015
Morrow, C. S., & Moore, D. L. (2020). Vimentin’s side gig: Regulating cellular proteostasis in mammalian systems. Cytoskeleton (Hoboken, N.J.), 77(11), 515–523. https://doi.org/10.1002/cm.21645
Morrow, C. S., Porter, T. J., Xu, N., Arndt, Z. P., Ako-Asare, K., Heo, H. J., Thompson, E. A. N., & Moore, D. L. (2020). Vimentin Coordinates Protein Turnover at the Aggresome during Neural Stem Cell Quiescence Exit. Cell stem cell, 26(4), 558–568.e9. https://doi.org/10.1016/j.stem.2020.01.018
Morrow, C. S., & Moore, D. L. (2019). Stem Cell Aging? Blame It on the Niche. Cell stem cell, 24(3), 353–354. https://doi.org/10.1016/j.stem.2019.02.011
Apara A, Galvao J, Wang Y, Blackmore M, Trillo A, Iwao K, Brown DP Jr, Fernandes KA, Huang A, Nguyen T, Ashouri M, Zhang X, Shaw PX, Kunzevitzky NJ, Moore DL, Libby RT, Goldberg JL. (2017). KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS. Journal of Neuroscience, 37(40):9632-9644. doi: 10.1523/JNEUROSCI.0643-16.2017.