Kitra Lily Cates

All Publications

• Modeling late-onset Alzheimer's disease neuropathology via direct neuronal reprogramming. Science (New York, N.Y.) Sun, Z., Kwon, J., Ren, Y., Chen, S., Walker, C. K., Lu, X., Cates, K., Karahan, H., Sviben, S., Fitzpatrick, J. A., Valdez, C., Houlden, H., Karch, C. M., Bateman, R. J., Sato, C., Mennerick, S. J., Diamond, M. I., Kim, J., Tanzi, R. E., Holtzman, D. M., Yoo, A. S. 2024; 385 (6708): adl2992

  Abstract

  Late-onset Alzheimer's disease (LOAD) is the most common form of Alzheimer's disease (AD). However, modeling sporadic LOAD that endogenously captures hallmark neuronal pathologies such as amyloid-beta (Abeta) deposition, tau tangles, and neuronal loss remains an unmet need. We demonstrate that neurons generated by microRNA (miRNA)-based direct reprogramming of fibroblasts from individuals affected by autosomal dominant AD (ADAD) and LOAD in a three-dimensional environment effectively recapitulate key neuropathological features of AD. Reprogrammed LOAD neurons exhibit Abeta-dependent neurodegeneration, and treatment with beta- or gamma-secretase inhibitors before (but not subsequent to) Abeta deposit formation mitigated neuronal death. Moreover inhibiting age-associated retrotransposable elements in LOAD neurons reduced both Abeta deposition and neurodegeneration. Our study underscores the efficacy of modeling late-onset neuropathology of LOAD through high-efficiency miRNA-based neuronal reprogramming.

  View details for DOI 10.1126/science.adl2992

  View details for PubMedID 39088624

• Evaluation of an 8-week high school science communication course designed to read, write, and present scientific research ADVANCES IN PHYSIOLOGY EDUCATION Radyk, M. D., Spatz, L. B., Adkins-Threats, M. L., Cates, K., St Pierre, C. L. 2023; 47 (4): 910-918

  Abstract

  The development of science writing and presentation skills is necessary for a successful science career. Too often these skills are not included in pre- or postsecondary science, technology, engineering, and mathematics (STEM) education, leading to a disconnect between high schoolers' expectations for college preparedness and the skills needed to succeed in college. The Young Scientist Program Summer Focus recruits high school students from historically marginalized backgrounds to participate in 8-week summer internships at Washington University in St. Louis. Students conduct hands-on biomedical research projects under the mentorship of Washington University scientists (graduate students, postdoctorates, lab staff). Here, we present the curriculum for a science communication course that accompanies this early research experience. The course is designed to strengthen students' communication skills (critical reading, writing, presenting, and peer review) through a combination of weekly lectures and active learning methods. It prepares students for the capstone of their summer internship: writing a scientific paper and presenting their results at a closing symposium. We administered pre- and postprogram surveys to four Summer Focus cohorts to determine whether the course met its learning objectives. We found significant improvements in students' self-confidence in reading, interpreting, and communicating scientific data. Thus, this course provides a successful model for introducing science literacy and communication skills that are necessary for any career in STEM. We provide a detailed outline of the course structure and content so that this training can be incorporated into any undergraduate and graduate research programs.NEW & NOTEWORTHY Strong communication skills are necessary for a successful scientific career. Here, we describe the curriculum for a science communication course designed to accompany high school students participating in a summer biomedical research program. The course aims to improve their scientific literacy and communication skills. Students learn to read and understand scientific literature, write a paper about their summer research project, present their results, and provide feedback to peers. We found significant improvements in students' self-confidence in reading, interpreting, and communicating scientific data after completing the course. This successful model serves as a guide for students participating in their first research experience and provides the skills for success in future science, technology, engineering, and mathematics education and careers. The curriculum presented here can be easily adapted for any research program, including undergraduate summer research experiences and graduate student laboratory rotations.

  View details for DOI 10.1152/advan.00085.2022

  View details for Web of Science ID 001127097700001

  View details for PubMedID 37769043

  View details for PubMedCentralID PMC10854798

• Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs. Cell stem cell Cates, K. n., McCoy, M. J., Kwon, J. S., Liu, Y. n., Abernathy, D. G., Zhang, B. n., Liu, S. n., Gontarz, P. n., Kim, W. K., Chen, S. n., Kong, W. n., Ho, J. N., Burbach, K. F., Gabel, H. W., Morris, S. A., Yoo, A. S. 2020

  Abstract

  Cell-fate conversion generally requires reprogramming effectors to both introduce fate programs of the target cell type and erase the identity of starting cell population. Here, we reveal insights into the activity of microRNAs miR-9/9∗ and miR-124 (miR-9/9∗-124) as reprogramming agents that orchestrate direct conversion of human fibroblasts into motor neurons by first eradicating fibroblast identity and promoting uniform transition to a neuronal state in sequence. We identify KLF-family transcription factors as direct target genes for miR-9/9∗-124 and show their repression is critical for erasing fibroblast fate. Subsequent gain of neuronal identity requires upregulation of a small nuclear RNA, RN7SK, which induces accessibilities of chromatin regions and neuronal gene activation to push cells to a neuronal state. Our study defines deterministic components in the microRNA-mediated reprogramming cascade.

  View details for DOI 10.1016/j.stem.2020.08.015

  View details for PubMedID 32961143