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

Throughout life, stem cells are responsible for replenishing and regenerating tissue, fundamentally maintaining “youthfulness.” However, with aging, this ability is decreased, resulting in effects such as cognitive impairment, reduced immune response, deterioration of skeletal muscle, and difficulty in wound healing, for example. To develop methods to improve or rescue aging of somatic stem cells, we must understand not only how they age, but also how they remain young. Recently, we have shown that neural stem cells (NSCs) asymmetrically segregate cargoes (e.g. damaged proteins) when they divide, leaving one daughter cell more “clean” than the other. In addition, we have identified a diffusion barrier in the endoplasmic reticulum membrane in dividing NSCs that may limit the movement of these cargoes. Indeed, we have found that diffusion barrier strength weakens with age, correlating with a more symmetric distribution of aging factors, suggesting that this may be a mechanism for the segregation (Moore et al, 2015, Science).

In mammalian NSCs, the daughter cell which inherits the damage has a slower proliferation rate than the more “clean” daughter, suggesting that this process may be utilized by the cell as a method of cellular rejuvenation (Moore et al, 2015, Science). We hypothesize that stem cells use the asymmetric segregation of cargoes as a mechanism to remain “young,” and that loss of this asymmetry and the weakening of the diffusion barrier with age greatly contributes to the stem cell aging phenotype seen in the body.

The research in my lab focuses on identifying the mechanisms that stem cells use to create the asymmetric segregation of cargoes, to identify what other components are segregated, and to use this knowledge to improve stem cell aging. We use mammalian embryonic stem cells and adult neural stem cells as model systems in our research, with interest in broadening our somatic stem cell portfolio. We employ cell biology, biochemistry, molecular biology, genetics, and computational approaches to address our questions. Our lab specifically focuses on using advanced live imaging technologies, including FLIP, FRAP, photoactivation, 4D timelapse, and computer learning-based high-throughput imaging to interrogate cargoes in mitotic stem cells. If you can see it, you can believe it.

Selected Publications

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.